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World Health Organization

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• National Public Radio - What Does The World Health Organization Do?
• Official Site of the World Health Organization

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World Health Organization (WHO) , specialized agency of the United Nations (UN) established in 1948 to further international cooperation for improved public health conditions. Although it inherited specific tasks relating to epidemic control, quarantine measures, and drug standardization from the Health Organization of the League of Nations (set up in 1923) and the International Office of Public Health at Paris (established in 1907), WHO was given a broad mandate under its constitution to promote the attainment of “the highest possible level of health” by all peoples. WHO defines health positively as “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” Each year WHO celebrates its date of establishment, April 7, 1948, as World Health Day.

With administrative headquarters in Geneva , governance of WHO operates through the World Health Assembly, which meets annually as the general policy-making body, and through an Executive Board of health specialists elected for three-year terms by the assembly. The WHO Secretariat , which carries out routine operations and helps implement strategies, consists of experts, staff, and field workers who have appointments at the central headquarters or at one of the six regional WHO offices or other offices located in countries around the world. The agency is led by a director general nominated by the Executive Board and appointed by the World Health Assembly. The director general is supported by a deputy director general and multiple assistant directors general, each of whom specializes in a specific area within the WHO framework, such as family, women’s, and children’s health or health systems and innovation . The agency is financed primarily from annual contributions made by member governments on the basis of relative ability to pay. In addition, after 1951 WHO was allocated substantial resources from the expanded technical-assistance program of the UN.

WHO officials periodically review and update the agency’s leadership priorities. Over the period 2014–19, WHO’s leadership priorities were aimed at:

1. Assisting countries that seek progress toward universal health coverage

2. Helping countries establish their capacity to adhere to International Health Regulations

3. Increasing access to essential and high-quality medical products

4. Addressing the role of social, economic, and environmental factors in public health

5. Coordinating responses to noncommunicable disease

6. Promoting public health and well-being in keeping with the Sustainable Development Goals, set forth by the UN.

The work encompassed by those priorities is spread across a number of health-related areas. For example, WHO has established a codified set of international sanitary regulations designed to standardize quarantine measures without interfering unnecessarily with trade and air travel across national boundaries. WHO also keeps member countries informed of the latest developments in cancer research, drug development, disease prevention, control of drug addiction, vaccine use, and health hazards of chemicals and other substances.

WHO sponsors measures for the control of epidemic and endemic disease by promoting mass campaigns involving nationwide vaccination programs, instruction in the use of antibiotics and insecticides , the improvement of laboratory and clinical facilities for early diagnosis and prevention, assistance in providing pure-water supplies and sanitation systems, and health education for people living in rural communities . These campaigns have had some success against AIDS , tuberculosis , malaria , and a variety of other diseases. In May 1980 smallpox was globally eradicated , a feat largely because of the efforts of WHO. In March 2020 WHO declared the global outbreak of COVID-19 , a severe respiratory illness caused by a novel coronavirus that first appeared in Wuhan, China, in late 2019, to be a pandemic . The agency acted as a worldwide information centre on the illness, providing regular situation reports and media briefings on its spread and mortality rates; dispensing technical guidance and practical advice for governments, public health authorities, health care workers, and the public; and issuing updates of ongoing scientific research. As pandemic-related infections and deaths continued to mount in the United States , Pres. Donald J. Trump accused WHO of having conspired with China to conceal the spread of the novel coronavirus in that country in the early stages of the outbreak. In July 2020 the Trump administration formally notified the UN that the United States would withdraw from the agency in July 2021. The U.S. withdrawal was halted by Trump’s successor, Pres. Joe Biden , on the latter’s first day in office in January 2021.

In its regular activities WHO encourages the strengthening and expansion of the public health administrations of member nations, provides technical advice to governments in the preparation of long-term national health plans, sends out international teams of experts to conduct field surveys and demonstration projects, helps set up local health centres, and offers aid in the development of national training institutions for medical and nursing personnel. Through various education support programs, WHO is able to provide fellowship awards for doctors, public-health administrators, nurses, sanitary inspectors, researchers, and laboratory technicians.

The first director general of WHO was Canadian physician Brock Chisholm, who served from 1948 to 1953. Later directors general of WHO included physician and former prime minister of Norway Gro Harlem Brundtland (1998–2003), South Korean epidemiologist and public health expert Lee Jong-Wook (2003–06), and Chinese civil servant Margaret Chan (2007–17). Ethiopian public health official Tedros Adhanom Ghebreyesus became director general of WHO in 2017.

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Lesson Plan: Role of the World Health Organization

Role of the World Health Organization

Christian McMillen talked about the origin of the World Health Organization and its role throughout history.

Description

The World Health Organization was started after World War II as an endeavor to coordinate efforts to combat infectious diseases as they spread around the world. Over the decades, other organizations have stepped into this role as well. The World Health Organization (WHO) declared COVID-19 a pandemic but was also criticized for its response. President Trump withdrew support from WHO, but President Biden renewed support his first day in office. In this lesson, students investigate the role of the organization and decide if they think the United States should support WHO.

This lesson offers several options for you to use with your students whether you are teaching in class, using a hybrid model, or engaging through distance learning. It can be completed in steps as a class or students can move at their own pace and complete the activities independently.

You can post links to the videos in the lesson along with the related handouts and engage in discussion to share responses on a discussion board or learning management system.

You can also save and share the following documents for students to use with this lesson.

Handout; World Health Organization Vocabulary Chart (Google Doc)

Handout with Questions: The Role of the World Health Organization (Google Doc)

In Google, choose "File" then "Make a Copy" to get your own copy. You can make any needed adjustments in the instructions such as which activities students need to complete, when it is due, etc. and then make it available to them via Google.

Discuss the following questions with students:

What makes a disease a pandemic?

In what ways could a global organization that addresses pandemics be helpful?

• What could be some potential shortcomings?

INTRODUCTION:

As a class, watch the video clip below and use the guiding questions for class discussion.

Video Clip 1: Role of the World Health Organization (3:22)

What is the purpose of the World Health Organization?

What are examples of what the WHO has done?

• Why is the role of the WHO less involved now than at its origin?

EXPLORATION:

Have students view the following video clips and respond to the accompanying questions on the handout. They can watch each video independently or view a video with a partner.

Video Clip 2: WHO Director General declares COVID-19 a Pandemic (2:55)

Dr. Tedros Adhanom Gebreyesus, Director-General of the World Health Organization, 'sounds the alarm bell' that COVID-19 can be characterized as a pandemic.

Why did WHO declare COVID-19 a pandemic?

• What difference do you think it makes if the WHO labels a disease as a ‘pandemic’?

Video Clip 3: The National Institute of Allergy and Infectious Diseases and the Federal Bureaucracy (5:52)

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases since 1984 talked about the role of the NIAID and how the institute works with other parts of the US government and organizations like the World Health Organization.

How does the United States Government approach preparation for infectious diseases?

What specific diseases has this part of the government dealt with in the past?

• How do the different health organizations work together?

Video Clip 4: China and the World Health Organization (4:01)

After President Trump announced that the United States would cut funding for the World Health Organization (WHO), Brett Schaefer of the Heritage Foundation talked about the decision and China's role in the organization. He also discussed the structure of the organization and the events that led to the current coronavirus outbreak.

How does the World Health Organization work?

• According to Brett Schaeffer of the Heritage Foundation, how was this a problem with China?

Video Clip 5: Misinformation during Public Health Emergencies (2:47)

Reid Wilson, author of "Epidemic: Ebola and the Global Scramble to Prevent the Next Killer Outbreak" talked about how misinformation can impact the spread of pandemics. He talked about examples of misinformation during the Ebola outbreak in Africa and COVID-19 in the United States.

What are infomedics during pandemics?

What are some examples of infodemics?

• According to Reid Wilson, how do we combat the dangers of misinformation during pandemics?

CONCLUDING ACTIVITY:

After discussing the information presented in the videos, students will prepare an argument for increasing or decreasing the U.S. government’s current level of support using evidence from the videos and additional outside resources.

Students will respond to the following prompt:

President Trump cut funding to the WHO and President Biden renewed our membership. Should the United States increase or decrease our support of the World Health Organization? What makes you say that?

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What Does the World Health Organization Do?

• The WHO is the UN agency responsible for coordinating international health efforts.
• The agency has undergone some reforms in recent years, but still faces criticism over budget constraints and slow responses to health emergencies.
• President Biden reversed his predecessor’s move to withdraw the United States from the WHO amid the COVID-19 pandemic.

Introduction

The World Health Organization (WHO) is the UN agency charged with spearheading international public health efforts. Over its nearly seventy-five years, the WHO has logged both successes, such as eradicating smallpox, and perceived failures, such as its delayed response to the Ebola outbreak in 2014.

In response, the WHO has undertaken reforms to improve its ability to fight future epidemics and boost the health of the hundreds of millions of people still living in extreme poverty. However, the WHO is in an uphill battle to loosen its rigid bureaucracy and it faces an increasingly troublesome budget. The COVID-19 pandemic has proved to be another monumental challenge for the health agency, sparking fresh debate over its effectiveness.

Why was the WHO established?

• World Health Organization (WHO)
• Public Health Threats and Pandemics
• International Organizations
• Global Governance

Created in 1948 as part of the United Nations, the WHO has a broad mandate to guide and coordinate international health policy. Its primary activities include developing partnerships with other global health initiatives, conducting research, setting norms, providing technical support, and monitoring health trends around the world. Over the decades, the WHO’s remit has expanded from its original focus on women’s and children’s health, nutrition, sanitation, and fighting malaria and tuberculosis.

What does the WHO do?

Daily news brief, a summary of global news developments with cfr analysis delivered to your inbox each morning.  weekdays., the world this week, a weekly digest of the latest from cfr on the biggest foreign policy stories of the week, featuring briefs, opinions, and explainers. every friday., think global health.

A curation of original analyses, data visualizations, and commentaries, examining the debates and efforts to improve health worldwide.  Weekly.

Today, the WHO monitors and coordinates activities concerning many health-related issues, including genetically modified foods, climate change, tobacco and drug use, and road safety. The WHO is also an arbiter of norms and best practices. Since 1977, the organization has maintained a list of essential medicines it encourages hospitals to stock; it has since made a similar list of diagnostic tests. The agency also provides guidance on priority medical devices, such as ventilators and X-ray and ultrasound machines.

Some of the WHO’s most lauded successes include its child vaccination programs, which contributed to the eradication of smallpox in 1979 and a 99 percent reduction in polio infections in recent decades, and its leadership during the 2003 severe acute respiratory syndrome (SARS) epidemic. The agency has the exclusive authority to declare global health emergencies, which it has done several times since its members granted it the power in 2007. At present, the WHO’s work includes combating the COVID-19 pandemic and other emergencies, as well as promoting refugees’ health.

In its 2019 strategy, the WHO identified three priorities [PDF] for its work over the next five years:

• providing health coverage to one billion more people;
• protecting one billion more people from health emergencies such as epidemics; and
• ensuring another one billion people enjoy better health and well-being, including protection from non-infectious diseases such as cancer.

The WHO’s strategic priorities are rooted in the United Nations’ Sustainable Development Goals , a set of seventeen objectives for ending poverty by 2030.

How is the WHO governed?

The WHO is headquartered in Geneva and has six regional and 150 country offices. It is controlled by delegates from its 194 member states, who vote on policy and elect the director general. Tedros Adhanom Ghebreyesus, previously Ethiopia’s foreign minister, was elected to a five-year term in 2017 and reelected in 2022. He is the WHO’s first leader from Africa , and his election was the first time all WHO countries had an equal vote.

WHO delegates set the agency’s agenda and approve an aspirational budget each year at the World Health Assembly. The director general is responsible for raising the lion’s share of funds from donors.

What is the WHO’s budget?

The current two-year goal (2022–23) is about $6.1 billion [PDF], with a sharp focus on managing consequences of the COVID-19 pandemic. Roughly 16 percent of the budget comes from mandatory dues paid by members; the rest is made up of voluntary donations from governments and private partners. In recent years, the top voluntary contributors have included Germany, the United States, the United Kingdom, and the Bill and Melinda Gates Foundation. Unlike dues, voluntary contributions are often earmarked for specific initiatives, which can complicate the WHO’s ability to set its own course.

The WHO has become increasingly dependent on voluntary contributions, which puts pressure on the organization to align its goals with those of its donors.

Over the past decade, the WHO has become increasingly dependent on voluntary contributions, which puts pressure on the organization to align its goals with those of its donors. For instance, President Donald Trump reportedly threatened to cut U.S. contributions in 2018 if other member states proceeded with a resolution to encourage breastfeeding. And in 2020, amid the COVID-19 pandemic, Trump announced he would cut all U.S. ties with the WHO, arguing it failed to take steps to reduce China’s influence over the body. Usually the top contributor, the United States fell to the second-largest donor, providing $680 million in 2020–21, or about 12 percent of the WHO’s budget. However, upon taking office in 2021, President Joe Biden issued an executive order to halt the withdrawal and reengage with the agency.

Some experts argued that the Trump administration’s moves seriously threatened the body’s effectiveness and cited budget cuts as a major factor in the WHO’s slow response to outbreaks. The eradication of polio could also place financial stress on the WHO, whose budget has for decades been bolstered by polio funding, and on lower-income countries that rely on international funding to keep up surveillance and immunization efforts.

How does the WHO fight global health emergencies?

Under the International Health Regulations (IHR), a legally binding framework drawn up in 2005 to prevent and mitigate health emergencies, WHO member states are required to monitor and report potential crises. Countries have historically been hesitant to report outbreaks, often because they’re fearful of economic repercussions. In 2003, for example, China denied for months that it was suffering an outbreak of the infectious disease that was eventually identified as SARS . Before the WHO declared China free of SARS in 2004, the disease killed more than three hundred people. In Ethiopia, Tedros himself was accused of downplaying cholera outbreaks while he was the country’s health minister; he denied these claims.

In an extraordinary crisis, the WHO can declare a public health emergency of international concern (PHEIC), which it has done six times: during the 2009 swine flu (H1N1) epidemic; in reaction to a reversal of progress in eradicating polio in 2014; amid the 2014 Ebola outbreak in West Africa; during the 2016 Zika virus outbreak in the Americas; once the ongoing Ebola epidemic reached the city of Goma in the Democratic Republic of Congo in 2019; and amid the global outbreak of the new coronavirus in 2020.

During a PHEIC, the WHO issues nonbinding guidance to its members on how they should respond to the emergency, including on potential travel and trade restrictions. It seeks to prevent countries in the surrounding region and beyond from overreacting and inflicting undue economic harm on the country in crisis. The WHO has hoped this would encourage affected countries to report outbreaks in a timely manner. However, experts say that, despite the WHO’s guidance, many countries continue to impose damaging travel and trade restrictions, a problem that was laid bare during the Ebola and COVID-19 crises. In an emergency, the WHO also spells out treatment guidelines and acts as a global coordinator , shepherding scientific data and experts to where they are most needed.

Additionally, the WHO provides guidance and coordination for emergencies that don’t rise to the level of a PHEIC. But declaring a PHEIC can help speed up international action and often encourages research on the disease in question, even if there is little risk of a pandemic. This was particularly true for the 2014 declaration for polio. At the same time, PHEIC declarations are contentious, and some argue that they can exacerbate ongoing outbreaks.

How has the WHO responded to COVID-19?

China alerted WHO officials of a growing outbreak in the city of Wuhan on December 31, 2019. The WHO declared a PHEIC one month later and drew up a strategic preparedness and response plan that initially called for $675 million in funding from donors, though it struggled to get contributions at first. (By late 2020, it had received $1.5 billion for its pandemic response fund, close to 90 percent of its goal for the year.) In March, after the virus had spread to more than one hundred countries, Tedros announced that the outbreak had reached pandemic levels. While such a designation generally does not affect how the WHO addresses a crisis, it amplifies the call for countries to develop their own emergency response plans.

As it has done in past health crises, the WHO has provided medical and technical guidance as its experts investigate the virus, particularly new variants, as well as coordinated with world leaders on their national responses. It has also distributed critical supplies to member states, including millions of diagnostic tests and personal protective equipment for health-care workers. Additionally, it has helped to lead the global vaccination effort: the WHO partnered with the Coalition for Epidemic Preparedness Innovations (CEPI) and Gavi, the Vaccine Alliance, to launch COVAX, a global initiative aimed at providing equitable access to COVID-19 vaccines. By mid-2022, COVAX had delivered about 1.5 billion doses , falling short of its goal to distribute 2 billion by the end of 2021.

However, the WHO’s response has been the subject of controversy. Many experts have raised concerns about the agency’s deference to Beijing and increasing Chinese influence over the institution. Among other criticisms, they say WHO officials accepted misinformation from the Chinese government as the outbreak unfolded, waited too long to declare an emergency, and have shunned Taiwan because of bias toward China. Trump was particularly critical of the agency and in May 2020 he announced an end to the U.S. relationship with the WHO. (Biden reversed course on the U.S. exit immediately after taking office.) In January 2021, a delegation of WHO scientists traveled to Wuhan to investigate the virus’s origin , though its findings were inconclusive and critics say Beijing constrained the group’s work. The WHO has since established a new advisory group to continue research on the issue.

What reforms has the WHO made?

Many critics have faulted the WHO for slow and poorly coordinated responses to outbreaks. That includes the 2014 Ebola outbreak, in which it waited five months before declaring a PHEIC, despite pleas from groups such as Doctors Without Borders. Responding to these criticisms, the organization instituted several reforms intended to improve its responses, including the creation of a reserve force of public health workers and a $100 million emergency fund. The WHO also added an incident management system that allows it to place medical responders, equipment, and supplies such as medicines on the ground right away while it coordinates a broader response.

Under Tedros, the WHO has tackled another of its most enduring problems: political friction between its headquarters and its six regional offices, which critics say have enjoyed too much autonomy. Some say that tension between Geneva and the WHO’s Africa office, in Brazzaville, Republic of Congo, contributed to the agency’s poor response to the 2014 Ebola outbreak. To assert its authority over these regional power bases, the WHO has begun requiring staff to rotate among posts around the world, similar to a policy at UNICEF. While some observers paint this and other changes as merely cosmetic, others have applauded the reforms. “There is much greater cooperation than there was in the past,” global health expert Ilona Kickbusch said at a 2020 CFR meeting .

More recently, the COVID-19 crisis has prompted calls for major reforms. In a rare special session of the WHO’s World Health Assembly in 2021, delegates initiated the drafting of a global treaty on pandemic prevention, preparedness, and response. The proposal for a pandemic treaty has sparked debate , however, and the deliberation process could take years. At the 2022 assembly, countries agreed on a U.S.-led proposal to strengthen the IHR by increasing member states’ accountability around disease outbreaks, though no changes have been formally approved.

“Pleas for strengthening the WHO have remained prominent,” writes CFR’s David P. Fidler for Think Global Health. “However, this goal faces serious obstacles ,” Fidler says, namely resistance from China, Russia’s war in Ukraine, and a lack of strong U.S. support for expanding the body’s authority and funding.

Recommended Resources

On The President’s Inbox podcast, CFR’s Stewart M. Patrick lays out what the WHO can and cannot do .

For Think Global Health, CFR’s David P. Fidler looks at the World Health Assembly’s slow steps toward global health reforms.

This CFR Independent Task Force report argues that the WHO has an important leadership role in public health emergencies but lacks the geopolitical heft to address their broader implications.

In Foreign Affairs , Laurie Garrett examines the WHO’s mishandling of the 2014 Ebola outbreak .

Plagues and the Paradox of Progress , a 2018 book by CFR’s Thomas J. Bollyky, discusses the WHO’s attempts to improve itself after the Ebola crisis.

This CFR Backgrounder describes ongoing global efforts  to eradicate polio.

• Infectious Diseases

Mia Speier contributed to this report.

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The Challenges of the World Health Organization: Lessons from the Outbreak of COVID-19

• First Online: 29 January 2021

Cite this chapter

• Virdzhiniya Petrova Georgieva 23  

Part of the book series: Balkan Yearbook of European and International Law ((BYEIL,volume 2020))

616 Accesses

The decisions adopted by the World Health Organization and the responses of its member states to the pandemic provoked by COVID-19 have revealed some of the challenges of this intergovernmental organization in its ability to provide efficient solutions to the health and health security problems of the international community at the beginning of the twenty-first century. WHO’s normative deficit has negatively affected the organization’s fight against the outbreak of the novel coronavirus. The chronic financial deficit of this institution has also determined its failures to control and eradicate the COVID-19 pandemic. Finally, the persistent violations of the rules and recommendations, adopted under WHO’s auspices, and the lack of control and accountability mechanisms in its legal framework have induced the little success of the institution’s intents to contain the global COVID-19 crisis. WHO could only surmount these challenges and continue to play a crucial role as a leader forum for states’ international cooperation in health and health security matters, if its members accept to reform the organization’s legal and institutional design.

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Introduction: Governance Challenges in the Management of the COVID-19 Pandemic in Africa

Preamble of WHO Constitution.

By virtue of article 2 of the WHO Constitution, the organization’s functions encompass the following: “to promote maternal and child health and welfare and to foster the ability to live harmoniously in a changing total environment; (m)to foster activities in the field of mental health, especially those affecting the harmony of human relations; (n) to promote and conduct research in the field of health; (o) to promote improved standards of teaching and training in the health, medical and related professions; (p) to study and report on, in co-operation with other specialized agencies where necessary, administrative and social techniques affecting public health and medical care from preventive and curative points of view, including hospital services and social security; (q) to provide information, counsel and assistance in the field of health; (r) to assist in developing an informed public opinion among all peoples on matters of health; (s) to establish and revise as necessary international nomenclatures of diseases, of causes of death and of public health practices; (t) to standardize diagnostic procedures as necessary; (u) to develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products; (v) generally to take all necessary action to attain the objective of the Organization.”

In this sense, article 21 of the WHO’s Constitution states: “Each Member undertakes that it will, within eighteen months after the adoption by the Health Assembly of a convention or agreement, take action relative to the acceptance of such convention or agreement. Each Member shall notify the Director-General of the action taken, and if it does not accept such convention or agreement within the time limit, it will furnish a statement of the reasons for non-acceptance. In case of acceptance, each Member agrees to make an annual report to the Director-General in accordance with Chapter XIV.”

Namely: “a) sanitary and quarantine requirements and other procedures designed to prevent the international spread of disease; b) nomenclatures with respect to diseases, causes of death and public health practices; (c) standards with respect to diagnostic procedures for international use; (d) standards with respect to the safety, purity and potency of biological, pharmaceutical and similar products moving in international commerce; (e) advertising and labelling of biological, pharmaceutical and similar products moving in international commerce” (article 2-k of WHO’s Constitution).

Many of these soft law instruments influenced the adoption of national legislation and international measures in health protection related matters. See Velasques ( 2012 ).

Examples of that kind of norms can be found in WHO’s Global Strategy on Diet, Physical Activity and Health (2010), Global Strategy to Reduce the Harmful Use of Alcohol (2008), Global Strategy for Women’s, Children’s and Adolescent’s Health (2016), Road Safety Strategies and Action Plans, Guide-lines for the Prevention of Maternal Diseases, etc.

Ostin ( 2015 ), p. 5.

The Tobacco Convention is aimed to control and regulate the cross-border effects of the tobacco epidemic.

The Nomenclature Regulations unify the standards for compilation and publication of the statistics of mortality and morbidity for the international classification of diseases. The last modification of the instrument was adopted in 2013.

The first International Sanitary Regulations were adopted at the end of the nineteenth century, in order to improve the international response against communicable diseases. In 1969, the instrument was named International Health Regulations (IHR) and was intended to control six infectious diseases: cholera, plague, yellow fever, smallpox, relapsing fever and typhus. After the spread of the Severe Acute Respiratory Syndrome (SARS), the World Health Assembly adopted the last modification of the IHR, in 2005.

In particular, states have the duty to notify to WHO detailed public health information “including case definitions, laboratory results, source and type of the risk, number of cases and deaths, conditions affecting the spread of the disease and the health measures employed” (article 6 of the IHR). This information is then shared by the WHO to all the other member states, who can entail consultation with each other and with the organization, in order to improve the measures adopted in response to the control and eradication of the disease.

According to this provision: “In determining whether an event constitutes a public health emergency of international concern, the Director-General shall consider: (a) information provided by the State Party; (b) the decision instrument contained in Annex 2; (c) the advice of the Emergency Committee; (d) scientific principles as well as the available scientific evidence and other relevant information; and (e) an assessment of the risk to human health, of the risk of international spread of disease and of the risk of interference with international traffic. 5. If the Director-General, following consultations with the State Party within whose territory the public health emergency of international concern has occurred, considers that a public health emergency of international concern has ended, the Director-General shall take a decision in accordance with the procedure set out in Article 49.”

These recommendations may include: “health measures (…) regarding persons, baggage, cargo, containers, conveyances, goods and/or postal parcels (…)” (Article 15-2 of the IHR), such as the application of medical exams, the requirement of additional documents and information concerning travelers destination, the disinfection and decontamination of conveyances, etc.

Article 13 of the IHR provides: “Each State Party shall develop, strengthen and maintain (…), the capacity to respond promptly and effectively to public health risks and public health emergencies of international concern as set out in Annex 1.”

According to article 13 of the IHR: “WHO shall publish, in consultation with Member States, guidelines to support States Parties in the development of public health response capacities.”

By virtue of this document: “The strengthening of national health systems and public health functions, based on the principles of primary health care and universal coverage, underpins many aspects of the Organization’s work – not just in terms of technical content but by providing a set of guiding values. In the last few years, the Organization’s work has focused on the building blocks of health systems (health service delivery, health workforce, health information systems, access to essential medicines, health systems financing, and leadership and governance). Now WHO’s focus will be to put those building blocks together into an integrated framework at community, district and national levels.” (WHO 2011 , p. 7).

Reuters ( 2020a ), New York Times ( 2020a ), and Euronews ( 2020 ).

New York Times ( 2020b ) and WHO ( 2020g ).

By virtue of WHO’s Constitution’s Preamble: “The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition.”

For example in article 5 (e) (iv) of the International Convention on the Elimination of All Forms of Racial Discrimination of 1965, in articles 11.1 (f) and 12 of the Convention on the Elimination of All Forms of Discrimination against Women of 1979 and in article 24 of the Convention on the Rights of the Child of 1989. The right to health is also recognized in the European Social Charter of 1961 as revised (art. 11), the African Charter on Human and Peoples’ Rights of 1981 (art. 16) and the Additional Protocol to the American Convention on Human Rights in the Area of Economic, Social and Cultural Rights of 1988 (art. 10).

According to this provision: “1. The States Parties to the present Covenant recognize the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. 2. The steps to be taken by the States Parties to the present Covenant to achieve the full realization of this right shall include those necessary for: (a) The provision for the reduction of the stillbirth-rate and of infant mortality and for the healthy development of the child; (b) The improvement of all aspects of environmental and industrial hygiene; (c) The prevention, treatment and control of epidemic, endemic, occupational and other diseases; (d) The creation of conditions which would assure to all medical service and medical attention in the event of sickness.”

The commentary states: “3.The right to health is closely related to and dependent upon the realization of other human rights, as contained in the International Bill of Rights, including the rights to food, housing, work, education, human dignity, life, non-discrimination, equality, the prohibition against torture, privacy, access to information, and the freedoms of association, assembly and movement.” It also “acknowledges that the right to health embraces a wide range of socio-economic factors that promote conditions in which people can lead a healthy life, and extends to the underlying determinants of health, such as food and nutrition, housing, access to safe and potable water and adequate sanitation, safe and healthy working conditions, and a healthy environment.”

According to article 32 of the IHR: “In implementing health measures under these Regulations, States Parties shall treat travellers with respect for their dignity, human rights and fundamental freedoms and minimize any discomfort or distress associated with such measures.”

Human Rights Watch ( 2020 ).

Tzeng ( 2020 ), pp. 1346–1351.

The CITES subjects the international trade of certain species to strict controls and includes them in three Appendices. CITES’ Appendices 1 includes 600 animal and 300 plant species, whose traffic is prohibited with very few exceptions. Appendices 2 covers 48,000 animal and 30,000 plant species, whose traffic is permitted but subject to strict controls, and Appendices 3 lists 135 animal and 15 plant species, the traffic of which is permitted under some control.

Challender et al. ( 2015 ), pp. 129–148.

WHO ( 2020a ).

According to article 16 of the Convention: “1. Each Contracting Party, recognizing that technology includes biotechnology, and that both access to and transfer of technology among Contracting Parties are essential elements for the attainment of the objectives of this Convention, undertakes subject to the provisions of this Article to provide and/or facilitate access for and transfer to other Contracting Parties of technologies that are relevant to the conservation and sustainable use of biological diversity or make use of genetic resources and do not cause significant damage to the environment.”

Toebes ( 2015 ), p. 300.

As stated by the Director-General of the WHO in 2011—Margaret Chan—in its Proposal for Reforms, the organization’s future work should “increasingly be concerned with building the capacity needed in countries to monitor and act on the environmental, economic and social determinants of health.” (Retrieved April 27, 2020 from https://apps.who.int/gb/ebwha/pdf_files/EBSS/EBSS2_2-en.pdf , p. 6).

Toebes (2015), p. 300.

Ostin ( 2015 ), p. 7.

In the first place, inspiring itself from the example of the global environmental treaties, the convention has created a COP (conference of parties), where states’ officials meet periodically to discuss subjects related to the interpretation and application of the Convention. The COP has adopted an additional Protocol to the convention, which is a treaty itself. Both the Convention and the Protocol have produced an important impact in states’ domestic legal system, as 80% of the members have adopted new legislation to implement their provisions at the national level (Nikogosian 2016 , p. 684).

WHO ( 2020b ).

US Department of Health and Human Services ( 2020 ).

According to the same document: “Voluntary contributions are the major source of the Organization’s funding2 and are expected to remain so. Voluntary contributions are often highly specified and not fully aligned with the programme budget. The majority of WHO’s funding is not sufficiently predictable or sustainable. There is an imbalance of funding for different programmes between technical cooperation and normative work, and between staff costs and activities.” See WHO ( 2011 ), p. 25.

In this sense, the initiative envisaged the “institution of a collective financing approach designed to secure a shared commitment by Member States and other donors to fully finance the Organization’s priorities as agreed by Member States in the programme budget” and “proposed that Member States and other donors increase the proportion of WHO’s income that is flexible by providing voluntary contributions that are less specified i.e. linked to higher level strategic components of the programme Budget”. See WHO ( 2011 ), p. 41.

WHO ( 2011 ), p. 27.

Ostin ( 2015 ), p. 8.

WHO ( 2011 ), p. 41.

Ostin ( 2015 ). p. 8.

Reuters ( 2014 ).

Wenham ( 2017 ), p. 1721.

New York Times ( 2014 ).

Wenham ( 2017 ).

WHO ( 2020c ).

WHO ( 2020d ).

WHO ( 2020i ).

WHO ( 2020e ).

CNBC ( 2020a ).

CNBC ( 2020b ).

Dupret ( 2014 ), p. 9.

Peterson ( 2019 ).

Ikenberry ( 2012 ).

For example, this country has a veto power in the UN Security Council and special voting rights at the two Bretton Woods institutions (the International Monetary Fund and the World Bank). In the same sense, the Director of the World Bank has to be an American citizen, NATO is dependent on the American military (super) power and the United States is the principal contributor to the budget of most of these organizations, including the UN.

BBC ( 2020a ).

DW ( 2020 ).

BBC ( 2020b ).

According to article 6: “The Director-General shall determine, on the basis of the information received, in particular from the State Party within whose territory an event is occurring, whether an event constitutes a public health emergency of international concern in accordance with the criteria and the procedure set out in these Regulations. (…) In determining whether an event constitutes a public health emergency of international concern, the Director-General shall consider: (a) information provided by the State Party; (b) the decision instrument contained in Annex 2; (c) the advice of the Emergency Committee; (d) scientific principles as well as the available scientific evidence and other relevant information; and (e) an assessment of the risk to human health, of the risk of international spread of disease and of the risk of interference with international traffic.” By virtue of article 7: “If a State Party has evidence of an unexpected or unusual public health event within its territory, irrespective of origin or source, which may constitute a public health emergency of international concern, it shall provide to WHO all relevant public health information. In such a case, the provisions of Article 6 shall apply in full.”

Burci ( 2020 ).

By virtue of this article: “Each State Party shall assess events occurring within its territory by using the decision instrument in Annex 2. Each State Party shall notify WHO, by the most efficient means of communication available, by way of the National IHR Focal Point, and within 24 hours of assessment of public health information, of all events which may constitute a public health emergency of international concern within its territory in accordance with the decision instrument, as well as any health measure implemented in response to those events.”

BBC ( 2020c ).

WHO ( 2020f ).

Aljazeera ( 2020a ).

Articles 42 and 43 of the IHR.

WHO ( 2020h ).

Burci ( 2019 ), p. 233.

According to article 61: “Each Member shall report annually to the Organization on the action taken and progress achieved in improving the health of its people.” In the same sense, in conformity with article 62: “Each Member shall report annually on the action taken with respect to recommendations made to it by the Organization and with respect to conventions, agreements and regulations.” Article 63 provides: “Each Member shall communicate promptly to the Organization important laws, regulations, official reports and statistics pertaining to health which have been published in the State concerned.”

Other treaties, establishing international organizations, set up mechanisms and sanctions that can be applied in such cases. Thus, for example, the Statute of the International Monetary Fund includes the imposition of sanctions against member States that do not respect the obligations incumbent on them by virtue of this agreement. The sanctions include the publication of public reports with sensible information on countries’ economic situation, the negative to afford financial assistance and credits to the State that has failed to fulfil its international obligations, the suspension of its voting rights, and, ultimately, its expulsion from the organization.

As mentioned above, article 43 of the regulations permits to the organization’s member states to implement additional measures to those provided by the Director-General’s recommendations after the declaration of a health emergency of international concern. However, the IHR do not include any negative consequences of the possible incompatibility between the measures adopted by the member states and those recommended by the Director-General. According to article 43-4: “After assessing information provided pursuant to paragraph 3 and 5 of this Article and other relevant information, WHO may request that the State Party concerned reconsider the application of the measures.” This “request” to “reconsider” the application of the measure does not include any duty to “put an end” to the inconsistent measures and exhorts state parties to the IHR to cooperate with the WHO, on a completely voluntary (and not compulsory) basis. State’s only binding obligation regarding their compliance with the IHR “is to report to the Health Assembly on the implementation of these Regulations” (article 54 of the IHR).

According to article 56 of the IHR: “in the event of a dispute between two or more States Parties concerning the interpretation or application of these Regulations, the States Parties concerned shall seek in the first instance to settle the dispute through negotiation or any other peaceful means of their own choice, including good offices, mediation or conciliation (…). In the event that the dispute is not settled by the means described under paragraph 1 of this Article, the States Parties concerned may agree to refer the dispute to the Director-General, who shall make every effort to settle it. 3. A State Party may at any time declare in writing to the Director-General that it accepts arbitration as compulsory with regard to all disputes concerning the interpretation or application of these Regulations to which it is a party or with regard to a specific dispute in relation to any other State Party accepting the same obligation. The arbitration shall be conducted in accordance with the Permanent Court of Arbitration Optional Rules for Arbitrating Disputes between Two States applicable at the time a request for arbitration is made. The States Parties that have agreed to accept arbitration as compulsory shall accept the arbitral award as binding and final. The Director-General shall inform the Health Assembly regarding such action as appropriate. 4. Nothing in these Regulations shall impair the rights of States Parties under any international agreement to which they may be parties to resort to the dispute settlement mechanisms of other intergovernmental organizations or established under any international agreement. 5. In the event of a dispute between WHO and one or more States Parties concerning the interpretation or application of these Regulations, the matter shall be submitted to the Health Assembly.”

Reuters ( 2020b ).

The Guardian ( 2020 ).

According to article 56: “A State Party may at any time declare in writing to the Director-General that it accepts arbitration as compulsory with regard to all disputes concerning the interpretation or application of these Regulations to which it is a party or with regard to a specific dispute in relation to any other State Party accepting the same obligation.”

Tzeng ( 2020 ).

By virtue of article 2 of the International Law Commission’s Draft Articles on Responsibility of States for Internationally Wrongful Acts: “There is an internationally wrongful act of a State when conduct consisting of an action or omission: (a) is attributable to the State under international law; and (b) constitutes a breach of an international obligation of the State.”

International Court of Justice, Declarations recognizing the jurisdiction of the Court as compulsory, Retrieved May 4, 2020 from https://www.icj-cij.org/en/declarations .

By virtue of this provision: “Any question or dispute concerning the interpretation or application of this Constitution which is not settled by negotiation or by the Health Assembly shall be referred to the International Court of Justice in conformity with the Statute of the Court, unless the parties concerned agree on another mode of settlement.”

According to article 62: “Each Member shall report annually on the action taken with respect to recommendations made to it by the Organization and with respect to conventions, agreements and regulations.” However, the obligation to report annually on the measure taken according to the IHR is different from the one established in the IHR regarding events that might constitute health emergencies of international concern. Consequently, it will be difficult to held China responsible for the violation of article 62 of the Constitution because of the delay of its reports to the WHO on the spread of COVID-19. In the same sense, article 63 of WHO’s constitutive statute provides: “Each Member shall communicate promptly to the Organization important laws, regulations, official reports and statistics pertaining to health which have been published in the State concerned.” The scope of this obligation is too general to fit with China’s response to COVID-19 and only covers published official reports and statistics. As noted above, China is accused to maintain secret and confidential relevant information on the novel virus, not only from the WHO, but also from the public opinion, in general.

Infobae ( 2020 ).

By virtue of article 12: “A State which becomes a Party to this Statute thereby accepts the jurisdiction of the Court with respect to the crimes referred to in article 5. 2. In the case of article 13, paragraph (a) or (c), the Court may exercise its jurisdiction if one or more of the following States are Parties to this Statute or have accepted the jurisdiction of the Court in accordance with paragraph 3: (…) (b) The State of which the person accused of the crime is a national.”

A situation, implicating the commission of international crimes can be referred to the ICC, directly, by the UN Security Council, even in relation to States that are not parties to the Rome Statute. However, the paradox of this procedure is that the Council can refer the nationals of other states to the ICC, but never the nationals of its five permanent members (the United States, France, the United Kingdom, Russia and China) because of their veto power during the referral.

In fact, article 12 of the Rome Statue establishes the possibility to determine the international criminal responsibility of nationals of a State non-signatory of the Statute, if “the State on the territory of which the conduct in question occurred or, if the crime was committed on board a vessel or aircraft, the State of registration of that vessel or aircraft” has ratified the treaty.

Aljazeera ( 2020b ).

The investigation will cover international crimes committed by nationals of a State that is not party to the Rome Statute (the United States) on the territory of other States parties to the convention (Afghanistan, Poland or Lithuania).

According to article 12-3 of the Rome Statute: “If the acceptance of a State which is not a Party to this Statute is required under paragraph 2, that State may, by declaration lodged with the Registrar, accept the exercise of jurisdiction by the Court with respect to the crime in question. The accepting State shall cooperate with the Court without any delay or exception in accordance with Part 9.”

The WHO’s officials enjoys a special legal status under the UN Convention on the Privileges and Immunities of the Specialized Agencies. According to article VI of this treaty: “Officials of the specialized agencies shall: (a) Be immune from legal process in respect of words spoken or written and all acts performed by them in their official capacity;” The broader scope of the term “legal process” seems to include immunity from jurisdiction in cases brought before domestic and international tribunals, such as the ICC. The question of the immunity from jurisdiction of the UN specialized agencies and/or other international organizations officials is not settled in the Rome Statute. Article 27 of the Statute provides: “1. This Statute shall apply equally to all persons without any distinction based on official capacity. In particular, official capacity as a Head of State or Government, a member of a Government or parliament, an elected representative or a government official shall in no case exempt a person from criminal responsibility under this Statute, nor shall it, in and of itself, constitute a ground for reduction of sentence.” However, the WHO is not a party to the Rome Statute and is not bound by this article. Even if its officials are nationals of a State that is party to the treaty, the special legal status of the officials derives from the organization’s own international personality, and is not related to the rights and duties of the organization’s member states. The UN and the ICC celebrated a Special Relationship Agreement in 2014. According to this agreement, if the ICC requests the testimony of a UN official, or wishes to exercise criminal jurisdiction over a person, who enjoys immunity under the UN Convention on Privileges and Immunities, the UN undertakes to cooperate and to waive the immunity. See Higgins et al. ( 2017 ), pp. 617–618. Thus, in the present case, the ICC could only hear a case related to the international criminal responsibility of a WHO’s official in relation to the outspread of COVID-19, if the UN Secretary-General expressly authorizes a waiver of its immunity from jurisdiction.

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Georgieva, V.P. (2021). The Challenges of the World Health Organization: Lessons from the Outbreak of COVID-19. In: Meškić, Z., Kunda, I., Popović, D.V., Omerović, E. (eds) Balkan Yearbook of European and International Law 2020. Balkan Yearbook of European and International Law, vol 2020. Springer, Cham. https://doi.org/10.1007/16247_2020_21

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The World Health Organization (WHO)

By Michael Marshall

The World Health Organization is the international body responsible for public health. Known as the WHO, it is part of the United Nations and was established in 1948. It is involved in many aspects of health policy and planning.

The WHO has played a major role in many of the public health successes of the last few decades. It was instrumental in the global eradication of smallpox , which used to be one of the world’s biggest killers. It has also run a campaign that has achieved the near-eradication of polio , and has worked for decades to reduce the threat from malaria .

When major disease outbreaks occur, the WHO coordinates the international response. It was front-and-centre in the 2014 Ebola outbreak , which it declared an international emergency. Similarly, it coordinated the response to the 2015-16 Zika outbreak . In 2020 it declared the outbreak of the covid-19 coronavirus a pandemic and urged governments to take strong measures to control the spread of the disease.

The WHO also sets international standards for diagnosing diseases and disorders. It maintains a catalogue called the International Classification of Diseases (ICD), which lists all the known conditions and the symptoms by which they should be diagnosed. The ICD is used around the world. It is regularly updated as medical knowledge advances, which often takes the WHO into tricky territory. In recent years the WHO has had to decide whether video gaming disorder and sex addiction are real disorders that could be diagnosed and treated.

Finally, the WHO promotes healthy lifestyles that reduce the risk of cancer , heart disease and other slow killers. It has mounted campaigns against smoking tobacco, and more recently against alcohol abuse . It also has a key role in maintaining healthy environments, for example setting standards for safe levels of air pollution. In recent years it has even begun measuring wellbeing – going beyond basic health measures to determine whether people are happy.

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World Health Organisation (WHO) - UPSC Notes

The World Health Organisation (WHO) is a specialized agency of the United Nations that looks into matters of public health. Established on April 7th, 1948, its headquarters is located in Geneva, Switzerland. WHO is an important topic for the IAS exam , as it is keeping in news concerning the Covid-19 outbreak. On 9th July, 2020, WHO created an Independent Panel for Pandemic Preparedness and Response (IPPR) to evaluate the world’s response to the COVID-19 pandemic.

World Health Organisation (WHO)

Recent Update:

To evaluate the world’s response to Coronavirus pandemic, Independent Panel for Pandemic Preparedness and Response (IPPR) has been created by the World Health Organisation. The main points related to it are:

• New Zealand former President Helen Clark and Liberia former President Ellen Johnson Sirleaf are co-chairs of  the IPPR, as announced by the WHO Director-General Tedros Adhanom Ghebreyesus
• The IPPR comes on the heels of the Landmark Resolution related to Covid-19 that was adopted in the 73rd World Health Assembly in May 2020.
• On 7 July 2020, President Trump formally notified the UN of his intent to withdraw the United States from the WHO. However, in January 2021, President Joe Biden announced plans to rejoin, and signed an executive order to that effect after his inauguration.
• In February 2021, the WHO team visited China in order to investigate the origins of the COVID-19 virus that allegedly had its origin in the Wuhan Virology Institute. The team will publish its findings in mid-march.
• WHO chief Tedros Adhanom Ghebreyesus on February 26, 2021 had lauded Prime Minister Narendra Modi’s commitment for supporting vaccine equity and sharing COVID-19 vaccines with over 60 countries across the world, hoping that other nations will follow his example.

Facts about WHO for UPSC

At the 1945 United Nations Conference on International Organization (also known as the San Francisco Conference), Szeming Sze, a delegate from the Republic of China (modern-day Taiwan), proposed the creation of an international health organization under the auspices of the new United Nations . Alger Hiss, the Secretary-General of the conference, recommended using a declaration to establish such an organization. 

As a result of these proceedings, the World Health Organisation came to be established in 1948. It became the first specialized agency of the United Nations to which every member subscribed.

• The WHO is headed by its Director-General and is headquartered in Geneva. Currently, the WHO has 194 member countries. 
• Full membership of the WHO is only guaranteed with the ratifying of the treaty known as the Constitution of the World Health Organisation.  To know more about Important Headquarters of International Organisations , visit the linked article.
• The member states of the WHO appoint delegates to the World Health Assembly, which is the supreme decision-making body. The World Health Assembly is attended by delegations from all Member States and determines the policies of the Organisation.
• On May 19, 2020, India was elected by the 73rd World Health Assembly to the Executive Board of the World Health Organisation for three years. Union Health Minister Harsh Vardhan took charge as the chairman of the WHO Executive Board on May 22. He succeeds Dr. Hiroki Nakatani of Japan.
• The WHO celebrates World Health Day annually on its formation day (7 April). The theme for 2020 was “Y ear of the Nurse and Midwife”.

WHO UPSC Notes:- Download PDF Here

What is the Overall Focus of the WHO?

The WHO Constitution states that the organization’s objective “is the attainment by all people of the highest possible level of health”.

The WHO fulfills this objective through the following functions:

• By playing a role as the directing and coordinating authority on international health work.
• Maintaining and establishing collaboration with the UN and any other appropriate bodies.
• Assisting governments, upon request, in strengthening their health services.
• Giving appropriate technical assistance and in case of emergencies, required aid upon the request or acceptance of governments.

What is the Health Policy of the WHO?

The WHO addresses government health policy with the following two aims:     

• To address the social and economic determinants of health through policies and programs “that enhance health equity and integrate pro-poor, gender-responsive, and human rights-based approaches”.
• To promote a healthier environment, intensify primary prevention, and influence public policies in all sectors to address the root causes of environmental threats to health”.

Contribution of WHO

The WHO has been instrumental in eradicating the suffering of millions all over the world through its assistance to various governments. Some of the important milestones include:

• Eradication of smallpox in 1980.
• The organization is close to eradicating Polio, a disease that affects mainly infants and young children. Due to eradication programs by the WHO, polio cases have come down by 99% since 1988. As of 2019, only three nations are suffering from polio – Nigeria, Afghanistan, and Pakistan.
• In 2008, the WHO initiated the observance of the ‘World Malaria Day’. This day is observed annually on April 25. Read more about this day in This Day in History dated April 25 .
• It focuses on infectious diseases like HIV, influenza, malaria, tuberculosis , and Ebola; and also other non-communicable diseases such as heart disease and cancer.
• It also takes efforts in the direction of maternity and infant healthcare, old-age care, and hygienic food and water for all.

Contributions of the WHO in India

India is a member of the WHO and the organization has its offices in various parts of the country. The WHO Country Office (WCO) is headquartered in New Delhi.

The WHO Country Cooperation Strategy (CCS) – India has been jointly developed by the Ministry of Health and Family Welfare of the GOI and the WCO. 

• Its chief aim is to contribute to improving health and equity in the country. 

The National Strategic Plan for Elimination of Malaria (2017-2022) was launched by the Union Minister for Health and Family Welfare. 

• Its chief aim is to eliminate Malaria by 2027. 
• The National Strategic Plan has formulated year wise elimination targets in various parts of the country. 
• It is formulated with the support of the World Health Organization’s Global Technical Strategy for Malaria (2016-2030).

What are the current challenges of WHO?

As an international organization, WHO has its fair share of challenges. Some of them are as follows:

• The WHO is largely dependent on funds from donors – usually from economically well-developed countries and organizations such as Melinda Gates Foundation – rather than a secured channel of funding.
• As a result, most of the WHO’s funding for crucial programs remain on the back burner as some of these programs also clash with the interests of the donors. 
• The effectiveness of the organization has come under question especially due to its disastrous handling of the Ebola outbreak in West Africa and the very recent coronavirus outbreak in 2019-20.
• Consequently, the WHO’s role as a leader in global health has been supplanted by other intergovernmental bodies such as the World Bank, and increasingly by big foundations.
• Initial concerns included the observation that while the WHO relies upon data provided and filtered by member states, China has had a “historical aversion to transparency and sensitivity to international criticism”. US President Donald Trump has been the most vocal of all the critics of the organization. This has led to the US’s withdrawal from the WHO.

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• Review Article
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• Published: 22 June 2022

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

• Joseph D. Khoury   ORCID: orcid.org/0000-0003-2621-3584 1 ,
• Eric Solary   ORCID: orcid.org/0000-0002-8629-1341 2 ,
• Oussama Abla 3 ,
• Yassmine Akkari   ORCID: orcid.org/0000-0002-3072-7388 4 ,
• Rita Alaggio 5 ,
• Jane F. Apperley   ORCID: orcid.org/0000-0002-1710-1794 6 ,
• Rafael Bejar   ORCID: orcid.org/0000-0002-5603-4598 7 ,
• Emilio Berti 8 ,
• Lambert Busque   ORCID: orcid.org/0000-0002-5375-3749 9 ,
• John K. C. Chan 10 ,
• Weina Chen   ORCID: orcid.org/0000-0001-5638-4371 11 ,
• Xueyan Chen 12 ,
• Wee-Joo Chng 13 ,
• John K. Choi   ORCID: orcid.org/0000-0002-2861-0180 14 ,
• Isabel Colmenero   ORCID: orcid.org/0000-0001-6859-187X 15 ,
• Sarah E. Coupland 16 ,
• Nicholas C. P. Cross   ORCID: orcid.org/0000-0001-5481-2555 17 ,
• Daphne De Jong 18 ,
• M. Tarek Elghetany 19 ,
• Emiko Takahashi   ORCID: orcid.org/0000-0001-8284-567X 20 ,
• Jean-Francois Emile   ORCID: orcid.org/0000-0002-6073-4466 21 ,
• Judith Ferry 22 ,
• Linda Fogelstrand 23 ,
• Michaela Fontenay 24 ,
• Ulrich Germing 25 ,
• Sumeet Gujral 26 ,
• Torsten Haferlach   ORCID: orcid.org/0000-0003-0196-2837 27 ,
• Claire Harrison 28 ,
• Jennelle C. Hodge 29 ,
• Shimin Hu   ORCID: orcid.org/0000-0001-7110-3814 1 ,
• Joop H. Jansen 30 ,
• Rashmi Kanagal-Shamanna   ORCID: orcid.org/0000-0001-7829-5249 1 ,
• Hagop M. Kantarjian   ORCID: orcid.org/0000-0002-1908-3307 31 ,
• Christian P. Kratz   ORCID: orcid.org/0000-0003-4120-5873 32 ,
• Xiao-Qiu Li 33 ,
• Megan S. Lim 34 ,
• Keith Loeb 35 ,
• Sanam Loghavi   ORCID: orcid.org/0000-0001-8980-3202 1 ,
• Andrea Marcogliese 19 ,
• Soheil Meshinchi 36 ,
• Phillip Michaels 37 ,
• Kikkeri N. Naresh   ORCID: orcid.org/0000-0003-3807-3638 35 ,
• Yasodha Natkunam   ORCID: orcid.org/0000-0002-9816-1018 38 ,
• Reza Nejati 39 ,
• German Ott 40 ,
• Eric Padron   ORCID: orcid.org/0000-0002-4707-7916 41 ,
• Keyur P. Patel 1 ,
• Nikhil Patkar   ORCID: orcid.org/0000-0001-9234-2857 42 ,
• Jennifer Picarsic 43 ,
• Uwe Platzbecker   ORCID: orcid.org/0000-0003-1863-3239 44 ,
• Irene Roberts 45 ,
• Anna Schuh   ORCID: orcid.org/0000-0002-3938-8490 46 ,
• William Sewell 47 ,
• Reiner Siebert 48 ,
• Prashant Tembhare   ORCID: orcid.org/0000-0002-9030-0415 42 ,
• Jeffrey Tyner   ORCID: orcid.org/0000-0002-2133-0960 49 ,
• Srdan Verstovsek   ORCID: orcid.org/0000-0002-6912-8569 31 ,
• Wei Wang   ORCID: orcid.org/0000-0001-6821-4556 1 ,
• Brent Wood 50 ,
• Wenbin Xiao   ORCID: orcid.org/0000-0001-8586-8500 51 ,
• Cecilia Yeung   ORCID: orcid.org/0000-0001-6799-2022 35 &
• Andreas Hochhaus   ORCID: orcid.org/0000-0003-0626-0834 52  

Leukemia volume  36 ,  pages 1703–1719 ( 2022 ) Cite this article

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• Haematological cancer

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

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Introduction.

The World Health Organization (WHO) classification of tumours is an evidence-based classification of cancers occurring within various organ systems. It is a standard for diagnosis, research, cancer registries, and public health monitoring worldwide. For the first time since the inception of the classification over 60 years ago, the current series (5th edition) has been developed within a unified relational database framework that encompasses the entirety of human cancers. Tumours of each organ system and across volumes (blue books) are classified hierarchically within this novel framework along taxonomy principles and a set of non-negotiables that include process transparency, bibliographic rigor, and avoidance of bias [ 1 , 2 ]. The development of the 5th edition is overseen by an editorial board that includes standing members —representatives from major medical and scientific organizations around the world—who oversee the entire series, in addition to expert members appointed for their leadership and contemporaneous expertise relevant to a particular volume [ 3 ]. The editorial board, in turn, identifies authors through an informed bibliometry process, with an emphasis on broad geographic representation and multidisciplinary expertise. By design, multidisciplinary author/editor groups (a total of 420 contributors) shared overlapping coverage of disease categories to ensure conceptual continuity and content harmonization. This approach reflects the ways in which the classification is meant to be implemented, with multidisciplinary input that emphasizes a holistic approach to patient management from diagnosis through disease monitoring.

The aim of this paper is to provide an overview of the new edition of the WHO classification for myeloid and histiocytic/dendritic tumours. The last edition of the haematolymphoid classification dates back to 2008 and was revised in 2017. An overview of the lymphoid tumours is provided in a companion manuscript [ 4 ].

The classification structure follows a lineage-based framework, flowing broadly from benign to malignant and branching down to category, family, type (disease/tumour), and subtype. Where possible, a triad of attributes was systematically applied and included: lineage + dominant clinical attribute + dominant biologic attribute. Lineage attribution rests on immunophenotyping with flow cytometry and/or immunohistochemistry. Dominant clinical attributes are general features of the untreated disease and include descriptors such as acute, chronic, cytopenia(s) (myelodysplasia) and cytosis(es) (myeloproliferation). Most biologic attributes include gene fusions , rearrangements , and mutations . Fusions are part of the nomenclature of types/subtypes when the identities of both implicated genes are required or often desirable criteria for diagnosis (e.g., PML :: RARA ). Rearrangements, a broad term that encompasses a range of structural genomic alterations leading to gene fusions, are part of the nomenclature of types/subtypes when there are multiple possible fusion partner genes of a biologically dominant gene (e.g., KMT2A ). Of note, the use of the term rearrangements is maintained in the classification due to its wide usage across prior editions, although it is recognized that it is more appropriate for genomic modifications in genes consisting of various segments (e.g., immunoglobulin genes and T-cell receptor genes). A deliberate attempt is made to prioritize classifying tumour types based on defining genetic abnormalities where possible.

Emerging entities are listed as disease subtypes under a novel rubric of other defined genetic alterations . This is envisioned as a landing spot in the classification to incorporate new/rare entities whose recognition is increasing as high-throughput molecular diagnostic tools become more available. This approach replaces the assignment of provisional status to such entities. It is recognized that the diagnosis of such subtypes might not be feasible in all practice settings. A set of decision support guidelines was adopted to aid in determining what subtypes would qualify in this context; they include: (1) having distinct molecular or cytogenetic features driven by established oncogenic mechanisms; (2) not meeting subtype criteria under other tumour types with defining genetic abnormalities; (3) having distinct pathologic and clinical features, including - but not limited to - response to therapeutic interventions; and, (4) at least two quality peer-review publications by distinct investigator groups.

The application of this classification is predicated on integrating morphologic (cytology and histology), immunophenotypic, molecular and cytogenetic data. This is in line with previous editions, with expanded numbers of disease types and subtypes that are molecularly defined. It is hoped that the genetic underpinnings of the classification will prompt the provision of health resources to ensure that the necessary genetic testing platforms are available to peruse the full potential of the classification. Notwithstanding, the full published classification will include listing of essential diagnostic criteria that have the broadest possible applicability, particularly in limited resource settings. A further aid to broader applicability is the improved hierarchical structure of the classification, which permits reverting to family (class)-level definitions when detailed molecular genetic analyses may not be feasible; this approach is further elaborated on in the introduction of the blue book.

In line with the rest of the WHO 5th edition series, the classification of myeloid and histiocytic/dendritic neoplasms follows the Human Genome Organization Gene Nomenclature Committee recommendations, including the new designation of gene fusions using double colon marks (::) [ 5 ].

Clonal haematopoiesis

Clonal haematopoiesis (CH) refers broadly to the presence of a population of cells derived from a mutated multipotent stem/progenitor cell harbouring a selective growth advantage in the absence of unexplained cytopenias, haematological cancers, or other clonal disorders. The incidence of CH increases with age [ 6 ]. Substantial advances in understanding the molecular genetics and public health implications of CH took place since the last classification, including recognition of their association with increased overall mortality, cardiovascular diseases, and myeloid malignancies. More specific emerging associations, such as those characterizing the VEXAS ( v acuoles, E 1 enzyme, X -linked, a utoinflammatory, s omatic UBA1 mutations) syndrome [ 7 ], represent manifestations of the interplay between inflammation and CH/myeloid neoplasia that are being gradually uncovered. Inclusion of CH in the classification represents a key inaugural effort to define and codify such myeloid precursor lesions.

Clonal haematopoiesis of indeterminate potential (CHIP) is defined in the classification as a term referring specifically to CH harbouring somatic mutations of myeloid malignancy-associated genes detected in the blood or bone marrow at a variant allele fraction (VAF) of ≥ 2% (≥4% for X-linked gene mutations in males) in individuals without a diagnosed haematologic disorder or unexplained cytopenia [ 8 ]. (Supplemental Data Table  S1 ) The significance of variants detected at lower levels is unclear at present.

Clonal cytopenia of undetermined significance (CCUS) is defined as CHIP detected in the presence of one or more persistent cytopenias that are otherwise unexplained by haematologic or non-haematologic conditions and that do not meet diagnostic criteria for defined myeloid neoplasms. Cytopenia definitions are harmonized for CCUS, MDS, and MDS/MPN; they include Hb <13 g/dL in males and <12 g/dL in females for anaemia, absolute neutrophil count <1.8 ×10 9 /L for leukopenia, and platelets <150 × 10 9 /L for thrombocytopenia [ 9 ].

Summary Box:

CH is recognized as a category of precursor myeloid disease state.

CHIP and CCUS are formally defined.

Myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) are listed in Table  1 . The main types remain largely unchanged from the prior edition. Initial diagnostic evaluation of MPN continues to depend on close correlation between clinical features, molecular diagnostics, and usually morphologic evaluation of a trephine bone marrow biopsy. Most MPN patients are diagnosed in chronic phase (CP), which may progress into a blast phase (BP) associated with the accumulation of secondary cytogenetic and/or molecular aberrations.

Chronic myeloid leukaemia risk factors are refined, and accelerated phase is no longer required

Chronic myeloid leukaemia (CML) is defined by the BCR :: ABL1 fusion resulting from t(9;22)(q34;q11). The natural history of untreated CML before the introduction of targeted tyrosine kinase inhibitors (TKI) was biphasic or triphasic: an initial indolent CP followed by a blast phase (BP), with or without an intervening accelerated phase (AP). With TKI therapy and careful disease monitoring, the incidence of progression to advanced phase disease has decreased, and the 10-year overall survival rate for CML is 80–90% [ 10 , 11 ]. The designation of AP has thus become less relevant, where resistance stemming from ABL1 kinase mutations and/or additional cytogenetic abnormalities and the development of BP represent key disease attributes [ 12 , 13 ]. Accordingly, AP is omitted in the current classification in favour of an emphasis on high risk features associated with CP progression and resistance to TKI. Criteria for BP include: (1) ≥20% myeloid blasts in the blood or bone marrow; or (2) the presence of an extramedullary proliferation of blasts; or (3) the presence of increased lymphoblasts in peripheral blood or bone marrow. The optimal cutoff for lymphoblasts and the significance of low-level B-lymphoblasts remain unclear and require additional studies.

Minor changes in diagnostic criteria for BCR::ABL1 -negative myeloproliferative neoplasms

The classification retains an emphasis on distinguishing between polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) using diagnostic criteria established in previous editions, with minor refinements. Distinction between these types is based on integrating peripheral blood findings with molecular data and bone marrow morphologic evaluation findings, as none of these parameters alone provide sufficient diagnostic specificity.

Major diagnostic criteria for the diagnosis of PV include elevated haemoglobin concentration and/or haematocrit, accompanied by trilineage hyperplasia (panmyelosis), with pleomorphic mature megakaryocytes in the bone marrow, and NM_004972:JAK2 p.V617F or JAK2 exon 12 mutations. As the determination of increased red cell mass with 51 Cr-labeled red cells has become uncommon in routine clinical practice, it has been removed as a diagnostic criterion. The diagnostic criteria of ET are well-established and have not changed.

Primary myelofibrosis (PMF) is characterized by a proliferation of abnormal megakaryocytes and granulocytes in the bone marrow, which is associated in fibrotic stages with a polyclonal increase in fibroblasts that drive secondary reticulin and/or collagen marrow fibrosis, osteosclerosis, and extramedullary haematopoiesis. Recognizing prefibrotic PMF remains necessary to separate it not only from ET and PV but also from fibrotic PMF [ 14 ]. The importance of serial monitoring of bone marrow fibrosis and spleen size using reproducible and standardized criteria remain pertinent, especially for patients receiving JAK1/2 inhibitors. PV and ET progress to AP (10-19% blasts) and BP (≥20% blasts) in a minority of cases, but leukaemic transformation is more frequent in PMF, and leukaemia-free survival is shorter in fibrotic than prefibrotic PMF [ 15 , 16 ].

While JAK2 , CALR , and MPL mutations are considered driver events, mutations in other genes – particularly TET2 , ASXL1 , and DNMT3A – are found in over half of patients with MPN. Mutations affecting splicing regulators ( SRSF2, SF3B1, U2AF1, ZRSR2 ) and other regulators of chromatin structure, epigenetic functions and cellular signaling (e.g., EZH2, IDH1, IDH2, CBL, KRAS, NRAS, STAG2, TP53 ) are less common. These additional mutations are more frequent in PMF and advanced disease compared to PV and ET, and some are known to correlate with a poorer prognostic risk (e.g., EZH2, IDH1, IDH2, SRSF2, U2AF1 , and ASXL1 mutations in PMF).

Chronic neutrophilic leukaemia (CNL) is a BCR :: ABL1 -negative MPN characterized by sustained peripheral blood neutrophilia (white blood cell count (WBC) ≥ 25 × 10 9 / L, with ≥80% segmented neutrophils and bands), bone marrow hypercellularity due to neutrophilic granulocyte proliferation, and hepatosplenomegaly. CSF3R mutations are common in this disease and detected in >60% of cases [ 17 , 18 ].

Chronic eosinophilic leukaemia (CEL) is a multi-system disorder characterized by a sustained clonal proliferation of morphologically abnormal eosinophils and eosinophil precursors resulting in persistent hypereosinophilia in blood and bone marrow [ 19 , 20 , 21 ]. Several changes to the diagnostic criteria of CEL are introduced: (1) the time interval required to define sustained hypereosinophilia is reduced from 6 months to 4 weeks; (2) addition of requirement for both clonality and abnormal bone marrow morphology (e.g., megakaryocytic or erythroid dysplasia); and, (3) elimination of increased blasts (≥2% in peripheral blood or 5-19% in bone marrow) as an alternative to clonality. These criteria improve the distinction between CEL and entities such as idiopathic hypereosinophilic syndrome and hypereosinophilia of unknown significance [ 22 ]. As the criteria of CEL and its place relative to other disorders with eosinophilia have become well characterized, the qualifier “not otherwise specified” is no longer needed and has been omitted from the name.

As in prior editions, MPN, not otherwise specified (MPN-NOS) is a designation that should be reserved for cases with clinical, laboratory, morphologic, and molecular features of MPN but lacking diagnostic criteria of any specific MPN type or with features that overlap across distinct MPN types.

Juvenile myelomonocytic leukaemia is recognized as a myeloproliferative neoplasm of early childhood with frequent association with germline pathogenic gene variants

Juvenile myelomonocytic leukaemia (JMML) is a haematopoietic stem cell-derived myeloproliferative neoplasm of early childhood. The pathogenetic mechanism in at least 90% of cases involves unchecked activation of the RAS pathway. A diagnosis of JMML can be made by combining clinical, laboratory, and molecular criteria. Updates to diagnostic criteria include: (1) exclusion of KMT2A rearrangements; (2) elimination of monosomy 7 as a cytogenetic criterion; and, (3) emphasizing the significance of diagnostic molecular studies, particularly those aimed at demonstrating RAS pathway activation. The genetic background of JMML plays a major role in risk stratification and therapeutic approaches, with cases initiated by somatic mutations involving PTPN11 and germline pathogenic variants associated with neurofibromatosis type 1 being the most aggressive types, while some cases associated with pathogenic germline CBL variants undergoing occasionally spontaneous remission. The inclusion of JMML under MPN reflects its molecular pathogenesis and underscores the virtual absence of stigmata of bona fide myelodysplastic neoplasia in this disease.

CML phases consolidated into chronic and blast phases, with emphasis on risk features in chronic phase.

Diagnostic criteria of CEL are updated, and the qualifier NOS is omitted.

JMML is categorized under myeloproliferative neoplasms.

Mastocytosis

Mastocytosis comprises rare heterogeneous neoplasms characterized by an accumulation of abnormal mast cells in various organs or tissues, typically driven by constitutive activation of the KIT receptor. The pathology of mastocytosis is complex, and clinical features span a broad spectrum that may be modulated by the presence of comorbidities. Significant comorbidities include IgE-dependent allergies, vitamin D deficiency, and psychiatric, psychological or mental problems. The classification continues to recognize three disease types: systemic mastocytosis (SM), cutaneous mastocytosis (CM) and mast cell sarcoma (MCS) [ 23 ]. (Table  2 )

A somatic point mutation in the KIT gene at codon 816 is detected in >90% of patients with SM. Other rare activating KIT alterations include mutations in the extracellular (e.g., deletion of codon 419 on exon 8 or A502_Y503dup in exon 9), transmembrane (e.g., NM_000222:KIT p.F522C), or juxtamembrane (e.g., NM_000222:KIT p.V560G) domains, detected in <1% of advanced SM cases but enriched in cases of indolent SM. Most patients with advanced SM and NM_000222: KIT p.D816V have additional somatic mutations involving most frequently TET2, SRSF2, ASXL1, RUNX1 , and JAK2 . An associated haematologic (usually myeloid) neoplasm may be detected in these patients [ 24 ].

Diagnostic criteria for SM have been modified. Namely, expression of CD30 and the presence of any KIT mutation causing ligand-independent activation have been accepted as minor diagnostic criteria. Basal serum tryptase level >20 ng/ml, which should be adjusted in case of hereditary alpha-tryptasaemia, is a minor SM criterion [ 25 ]. In addition, bone marrow mastocytosis is now a separate subtype of SM characterized by absence of skin lesions and B-findings and a basal serum tryptase below 125 ng/ml. Classical B-findings (‘burden of disease’) and C-findings (‘cytoreduction-requiring’) have undergone minor refinements. Most notably, NM_000222: KIT p.D816V mutation with VAF ≥ 10% in bone marrow cells or peripheral blood leukocytes qualifies as a B-finding.

The classification recognizes well-differentiated systemic mastocytosis (WDSM) as a morphologic pattern that can occur in any SM subtype, characterized by round and well-granulated mast cells usually heavily infiltrating the bone marrow. In most patients with WDSM, KIT codon 816 mutation is not detected, and neoplastic mast cells are usually negative for CD25 and CD2 but positive for CD30 [ 26 ].

Diagnostic criteria for mastocytosis have been refined: CD30 and any KIT mutation are introduced as minor diagnostic criteria.

Bone marrow mastocytosis is a new SM subtype.

KIT D816V mutation with VAF ≥ 10% qualifies as a B-finding.

Myelodysplastic neoplasms

New terminology and grouping framework.

The classification introduces the term myelodysplastic neoplasms (abbreviated MDS) to replace myelodysplastic syndromes, underscoring their neoplastic nature and harmonizing terminology with MPN. These clonal haematopoietic neoplasms are defined by cytopenias and morphologic dysplasia. As indicated above, cytopenia definitions are adopted for consistency across CCUS, MDS, and MDS/MPN. Additionally, the recommended threshold for dysplasia is set at 10% for all lineages. MDS entities are now grouped as those having defining genetic abnormalities and those that are morphologically defined . (Table  3 ) It is posited that such reorganization enhances classification rigor by emphasizing genetically-defined disease types and ceding the prior emphasis on ‘risk-based’ grouping in the classification (based on blast percentage, ring sideroblasts, and number of lineages with dysplasia) in favour of more comprehensive risk-stratification schemes such as the Revised International Prognostic Scoring System for MDS (IPSS-R) [ 27 ]. An additional modification is a clarified terminology to distinguish between MDS with low blasts (MDS-LB) and MDS with increased blasts (MDS-IB), while retaining longstanding cutoffs.

MDS with defining genetic abnormalities

Myelodysplastic neoplasms with defining genetic abnormalities are grouped together and include: MDS with low blasts and isolated 5q deletion (MDS-5q), MDS with low blasts and SF3B1 mutation (MDS- SF3B1 ), and MDS with biallelic TP53 inactivation (MDS-bi TP53 ). The latter supersedes MDS-5q and MDS- SF3B1 .

The diagnostic criteria of MDS-5q have not changed. While recognized as factors that may potentially alter the biology and/or prognosis of the disease, the presence of SF3B1 or a TP53 mutation (not multi-hit) does not per se override the diagnosis of MDS-5q.

Recent studies have identified MDS- SF3B1 as a distinct disease type that includes over 90% of MDS with ≥5% ring sideroblasts [ 28 ]. The term MDS with low blasts and ring sideroblasts is retained as an acceptable alternative to be used for cases with wild-type SF3B1 and ≥15% ring sideroblasts. This permits inclusion of rare MDS cases harbouring driver mutations in other RNA splicing components.

Pathogenic TP53 alterations of any type (sequence variations, segmental deletions and copy neutral loss of heterozygosity) are detected in 7-11% of MDS [ 29 , 30 , 31 ]. Among these, about two-thirds of patients have multiple TP53 hits (multi-hit), consistent with biallelic TP53 alterations [ 29 ]. Biallelic TP53 (bi TP53 ) alterations may consist of multiple mutations or mutation with concurrent deletion of the other allele. This “multi-hit” mutational status results in a neoplastic clone that lacks any residual wild-type p53 protein. Clinical detection of biallelic TP53 alterations is based on sequencing analysis (covering at least exons 4 to 11) [ 29 , 32 ], often coupled with a technique to detect copy number status, usually fluorescence in situ hybridization with a probe set specific for the TP53 locus on 17p13.1 and/or array techniques (e.g., comparative genomic hybridization or single nucleotide polymorphism arrays) [ 33 ]. Loss of genetic material at the TP53 locus may also be inferred by next-generation sequencing [ 29 ]. A TP53 VAF ≥ 50% may be regarded as presumptive (not definitive) evidence of copy loss on the trans allele or copy neutral loss of heterozygosity when a constitutional TP53 variant can be ruled out. When two or more TP53 mutations are detected, they usually affect both alleles [ 29 ] and can be considered a multi-hit status. Over 90% of patients with MDS-bi TP53 have complex, mostly very complex (>3), karyotype [ 29 , 30 ] and thus are regarded as very high risk in IPSS-R [ 27 ]. Additional studies are needed to determine whether bi TP53 status is per se AML-defining, a point for consideration in future editions. Notwithstanding, published data suggests that MDS-bi TP53 may be regarded as AML-equivalent for therapeutic considerations [ 29 , 30 ].

MDS, morphologically defined

Hypoplastic MDS (MDS-h) is listed as a distinct MDS type in this edition. Long recognized as having distinctive features, MDS-h is associated with a T-cell mediated immune attack on haematopoietic stem and progenitor cells, along with oligoclonal expansion of CD8 + cytotoxic T-cells overproducing IFNγ and/or TNFα. Several features overlap across the triad of MDS-h, paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA), including an association with CH [ 34 , 35 , 36 ]. Many patients with MDS-h have sustainable responses to agents used in patients with AA (i.e., anti-thymocyte globulin, ATG). As such, an emphasis is placed on careful morphologic evaluation, typically requiring trephine biopsy evaluation in addition to evaluation of bone marrow smears and touch preparations, and detection of mutations and/or clonal cytogenetic abnormalities. Individuals with germline pathogenic variants in GATA2 , DDX41 , Fanconi anaemia (FA) or telomerase complex genes can have hypoplastic bone marrow and evolve to MDS and/or AML and do not respond to immunosuppressive treatment.

As the number of dysplastic lineages is usually dynamic and often represents clinical and phenotypic manifestation of clonal evolution – rather than per se defining a specific MDS type, the distinction between single lineage and multilineage dysplasia is now considered optional. The updated MDS classification scheme and the incorporation of CCUS in the classification obviates the need for “NOS” or “unclassifiable” attributes. Specifically, MDS, unclassifiable, which was present in the prior edition, is removed.

The boundary between MDS and AML is softened, but the 20% blast cutoff to define AML is retained

Reassessment of the bone marrow blast percentage defining the boundary of MDS-IB2 and AML has been advocated for several cogent reasons and in view of novel therapeutic approaches that show efficacy in patients currently classified as MDS or AML with 10-30% myeloid blasts [ 37 , 38 , 39 ]. Salient practical challenges underpinning arguments for such a reassessment include: (1) any blast-based cutoff is arbitrary and cannot reflect the biologic continuity naturally inherent in myeloid pathogenic mechanisms; (2) blast enumeration is subject to sampling variations/error and subjective evaluation; and, (3) no gold standard for blast enumeration exists, and orthogonal testing platforms can and often do produce discordant results. The pros and cons of merging MDS-IB2 with AML and adopting a 10% cutoff for what would be called MDS/AML were explored in multidisciplinary expert discussions and at editorial board meetings in the course of producing this classification. Lowering the blast cutoff to define AML was felt to suffer from the same challenges listed above and would merely replace one cutoff with another. Further, an arbitrary cutoff of 10% blasts to define AML (even if qualified as MDS/AML or AML/MDS) carries a risk of overtreatment. Accordingly, a balanced approach was adopted by eliminating blast cutoffs for most AML types with defining genetic alterations but retaining a 20% blast cutoff to delineate MDS from AML. Notwithstanding, there was broad agreement that MDS-IB2 may be regarded as AML-equivalent for therapeutic considerations and from a clinical trial design perspective when appropriate.

Childhood myelodysplastic neoplasms: Enhanced specificity of disease terminology introduced

Childhood MDS is a clonal haematopoietic stem cell neoplasm arising in children and adolescents (<18 years of age) leading to ineffective haematopoiesis, cytopenia(s), and risk of progression to AML. The annual incidence is 1-2 per million children, with 10-25% presenting with increased blasts. JMML, myeloid proliferations associated with Down syndrome, and MDS post cytotoxic therapy are excluded from this group and belong elsewhere in the classification. The qualifying term childhood MDS emphasizes that this category of myeloid neoplasms is biologically distinct from that seen in adults [ 40 , 41 ], underscoring the need to further elucidate its pathogenesis which remains incompletely understood

Childhood MDS with low blasts (cMDS-LB) replaces the former term “refractory cytopenia of childhood (RCC)”. It includes two subtypes: childhood MDS with low blasts, hypocellular; and, childhood MDS with low blasts, not otherwise specified (NOS). (Table  4 ) Exclusion of non-neoplastic causes of cytopenia such as infections, nutritional deficiencies, metabolic diseases, bone marrow failure syndromes (BMFS), and germline pathogenic variants remains an essential diagnostic prerequisite for childhood MDS with low blasts. Approximately 80% of cases show hypocellular bone marrow with features similar to severe aplastic anemia and other BMFS, requiring close morphologic examination to evaluate the distribution, maturation, and presence of dysplasia in haematopoietic lineages [ 42 ]. Some cytogenetic findings such as monosomy 7, 7q deletion, or complex karyotype are associated with an increased risk of progression to AML and typically treated with haematopoietic stem cell transplantation, while cases with normal karyotype or trisomy 8 can have an indolent course.

Childhood MDS with increased blasts (cMDS-IB) is defined as having ≥5% blasts in the bone marrow or ≥2% blasts in the peripheral blood. The genetic landscape of cMDS-IB and cMDS-LB is similar, and they both differ from MDS arising in adults. Acquired cytogenetic abnormalities and RAS-pathway mutations are more common in cMDS-IB compared to cMDS-LB [ 43 , 44 ].

Myelodysplastic syndromes renamed myelodysplastic neoplasms (abbreviated MDS).

MDS genetic types updated to include MDS-5q, MDS- SF3B1 and MDS-bi TP53

Hypoplastic MDS (MDS-h) is recognized as a distinct disease type.

MDS with low blasts (MDS-LB) is a new term that enhances clarity.

MDS with increased blasts (MDS-IB) is a new term that enhances clarity.

Terminology of childhood MDS types is updated.

Myelodysplastic/myeloproliferative neoplasms

This category of myeloid neoplasms is defined by overlapping pathologic and molecular features of MDS and MPN, often manifesting clinically with various combinations of cytopenias and cytoses. The definition of cytopenias is the same as that for MDS. The classification includes major revisions in the diagnostic criteria of CMML and terminology changes for other MDS/MPN types. (Table  5 )

Chronic myelomonocytic leukaemia diagnostic criteria, subtypes, and blast-based subgrouping criteria reflect diagnostic refinement and emphasize unifying characteristics

The prototype and most common MDS/MPN is chronic myelomonocytic leukaemia (CMML), which is characterized by sustained peripheral blood monocytosis and various combinations of somatic mutations involving epigenetic regulation, spliceosome, and signal transduction genes. Diagnostic criteria are revised to include prerequisite and supporting criteria. (Table  6 ) The first prerequisite criterion is persistent absolute (≥0.5 × 10 9 / L) and relative (≥10%) peripheral blood monocytosis. Namely, the cutoff for absolute monocytosis is lowered from 1.0 ×10 9 /L to 0.5 ×10 9 /L to incorporate cases formerly referred to as oligomonocytic CMML [ 45 , 46 , 47 ]. To enhance diagnostic accuracy when absolute monocytosis is ≥0.5 ×10 9 /L but <1.0 ×10 9 /L, detection of one of more clonal cytogenetic or molecular abnormality and documentation of dysplasia in at least one lineage are required. Abnormal partitioning of peripheral blood monocyte subsets is introduced as a new supporting criterion [ 48 , 49 ]. Additional studies are needed to determine the optimal approach to classifying individuals with unexplained clonal monocytosis [ 50 ] who do not fit the new diagnostic criteria of CMML.

Two disease subtypes with salient clinical and genetic features are now formally recognized based on WBC: myelodysplastic CMML (MD-CMML) (WBC < 13 × 10 9 /L) and myeloproliferative CMML (MP-CMML) (WBC ≥ 13 × 10 9 /L). MP-CMML is commonly associated with activating RAS pathway mutations and adverse clinical outcomes [ 51 ]. The blast-based subgroup of CMML-0 (<2% blasts in blood and <5% blasts in bone marrow) introduced in the previous edition has been eliminated in view of evidence that its addition provides no or limited prognostic significance [ 52 , 53 ].

Atypical chronic myeloid leukaemia is renamed MDS/MPN with neutrophilia, and other terminology updates

Diagnostic criteria for other MDS/MPN types were largely unchanged. The term MDS/MPN with neutrophilia replaces the term atypical CML. This change underscores the MDS/MPN nature of the disease and avoids potential confusion with CML. MDS/MPN with ring sideroblasts and thrombocytosis is redefined based on SF3B1 mutation and renamed MDS/MPN with SF3B1 mutation and thrombocytosis . The term MDS/MPN with ring sideroblasts and thrombocytosis has been retained as an acceptable term to be used for cases with wild-type SF3B1 and ≥15% ring sideroblasts. MDS/MPN, unclassifiable is now termed MDS/MPN, not otherwise specified ; this is in line with an intentional effort to remove the paradoxical qualifier “unclassifiable” from the entire classification.

CMML diagnostic criteria undergo major revisions, including lowering the cutoff for absolute monocytosis, adopting MD-CMML and MP-CMML subtypes, and eliminating CMML-0.

Atypical chronic myeloid leukaemia renamed MDS/MPN with neutrophilia.

MDS/MPN with ring sideroblasts and thrombocytosis redefined based on SF3B1 mutation and renamed MDS/MPN with SF3B1 mutation and thrombocytosis.

Acute myeloid leukaemia

Enhanced grouping framework permitting scalable genetic classification and deemphasizing blast enumeration where relevant.

The classification of AML is re-envisioned to emphasize major breakthroughs over the past few years in how this disease is understood and managed. Foremost is the separation of AML with defining genetic abnormalities from AML defined by differentiation. (Table  7 ) The latter eliminates the previously confusing use of the term AML NOS, under which types based on differentiation were listed. Another key change, as indicated above, is the elimination of the 20% blast requirement for AML types with defining genetic abnormalities (with the exception of AML with BCR :: ABL1 fusion and AML with CEBPA mutation). Removal of the blast cutoff requires correlation between morphologic findings and the molecular genetic studies to ensure that the defining abnormality is driving the disease pathology. This approach was deemed more appropriate than assigning another arbitrary lower bone marrow blast cutoff. A third component of the new structure is the introduction of a section on AML with other defined genetic alterations , a landing spot for new and/or uncommon AML subtypes that may (or may not) become defined types in future editions of the classification. As such, the overall AML classification structure continues to emphasize integration of clinical, molecular/genetic, and pathologic parameters and emphasis on clinicopathologic judgement.

AML with defining genetic abnormalities

While the classification retains much of the established diagnostic criteria for AML with PML :: RARA , AML with RUNX1 :: RUNX1T1 , and AML with CBF :: MYH11 , increased recognition of the importance of highly sensitive measurable residual disease (MRD) evaluation techniques, and the impact of concurrent molecular alterations reflect factors that impact patient management and therapeutic decisions in current practice. Namely, prognostic factors have expanded from KIT mutations, which are still relevant, to include additional cytogenetic features and MRD status post induction. The diagnostic criteria of AML with DEK :: NUP214 and AML with RBM15 :: MRTFA (formerly RBM15 :: MKL1 ) have also remained largely unchanged.

AML with BCR :: ABL1 and AML with CEBPA mutation are the only disease types with a defined genetic abnormality that require at least 20% blasts for diagnosis. The blast cutoff requirement is needed for the former to avoid overlap with CML. Distinguishing AML with BCR :: ABL1 from initial myeloid blast phase of CML can be challenging, and additional evidence continues to be needed to better characterize this AML type. There is insufficient data to support any change in the blast cutoff criterion for AML with CEBPA mutation [ 54 , 55 ].

Three AML types with characteristic rearrangements involving KMT2A, MECOM , and NUP98 are recognized. A blast count under 20% is acceptable based on studies demonstrating that patients with <20% blasts (MDS) and any of these rearrangements have clinical features that resemble those with higher blast counts. It is important to note that rearrangements involving these three genes, particularly NUP98 , may be cryptic on conventional karyotyping. AML with KMT2A rearrangement is the new term that replaces “AML with t(9;11)(p22;q23); KMT2A-MLLT3” . More than 80 KMT2A fusion partners have been described, with MLLT3, AFDN, ELL , and MLLT10 being most common. While not required, the identification of the fusion partner is desirable since it could provide prognostic information and may impact disease monitoring. Adult patients often present with high blast counts, usually with monocytic differentiation. In children particularly, AML with KMT2A :: MLLT3 and KMT2A :: MLLT10 show megakaryoblastic differentiation and/or low blast counts in bone marrow aspirate smears.

AML defined by mutations include AML with NPM1 and AML with CEBPA mutation. AML with NPM1 mutation can be diagnosed irrespective of the blast count, albeit again with emphasis on judicious clinicopathologic correlation. This approach aligns with data showing that cases previously classified as MDS or MDS/MPN with NPM1 progress to AML in a short period of time. Similar data have emerged from patients with CH who acquire NPM1 mutation. The definition of AML with CEBPA mutation has changed to include biallelic (biCEBPA) as well as single mutations located in the basic leucine zipper (bZIP) region of the gene (smbZIP- CEBPA ). The favourable prognosis associated with smbZIP- CEBPA has been demonstrated in cohorts of children and adults up to 70 years old. RUNX1 mutations in AML overlap with such a broad range of defining molecular features that it was determined to lack enough specificity to define a standalone AML type.

Several changes were introduced to the entity formerly designated AML with myelodysplasia-related changes, now called AML, myelodysplasia-related (AML-MR). This AML type is defined as a neoplasm with ≥20% blasts expressing a myeloid immunophenotype and harboring specific cytogenetic and molecular abnormalities associated with MDS, arising de novo or following a known history of MDS or MDS/MPN. Key changes include: (1) removal of morphology alone as a diagnostic premise to make a diagnosis of AML-MR; (2) update of defining cytogenetic criteria; and, (3) introduction of a mutation-based definition based on a set of 8 genes – SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2 , > 95% of which are present specifically in AML arising post MDS or MDS/MPN [ 56 , 57 ]. The presence of one or more cytogenetic or molecular abnormalities listed in Table  8 and/or history of MDS or MDS/MPN are required for diagnosing AML-MR.

AML with other defined genetic alterations represents a landing spot for new, often rare, emerging entities whose recognition is desirable to determine whether they might constitute distinct types in future editions. At present, subtypes under this heading include AML with rare genetic fusions.

AML defined by differentiation

This AML family includes cases that lack defining genetic abnormalities. (Table  9 ) It is anticipated that the number of such cases will diminish as discoveries provide novel genetic contexts for their classification. Notwithstanding, categorizing AML cases lacking defining genetic abnormalities based on differentiation offers a longstanding classification paradigm with practical, prognostic, and perhaps therapeutic implications.

The classification includes an updated comprehensive framework of differentiation markers and criteria, harmonized with those of mixed-phenotype acute leukaemia (MPAL) and early T-precursor lymphoblastic leukaemia/lymphoma (ETP-ALL) (see section below on acute leukaemia of ambiguous lineage). Indeed, the recent identification of BCL11B rearrangements in MPAL T/Myeloid, ETP-ALL, acute leukaemia of ambiguous lineage (ALAL) and a subset of AML with minimal differentiation suggests a biologic continuum across these entities, a finding with likely implications on future editions of the classification [ 58 , 59 , 60 , 61 ].

Acute erythroid leukaemia (AEL) (previously pure erythroid leukaemia, an acceptable related term in this edition) is a distinct AML type characterized by neoplastic proliferation of erythroid cells with features of maturation arrest and high prevalence of biallelic TP53 alterations. Diagnostic criteria include erythroid predominance, usually ≥80% of bone marrow elements, of which ≥30% are proerythroblasts (or pronormoblasts). The occurrence of AEL cases in which nucleated erythroid cells constitute less than 80% of bone marrow cellularity is recognized; such cases share the same clinicopathologic features of other AEL [ 62 , 63 ]. The central role that biallelic TP53 mutations play in this aggressive AML type is underscored [ 64 , 65 ]. The diagnosis of AEL supersedes AML-MR. De novo AEL and cases that arise following MDS or MDS/MPN share distinctive morphologic features, with prominent proerythroblast proliferation. Proerythroblast have been shown to play an important role in treatment resistance and poor prognosis in AML patients [ 66 , 67 ].

Several molecular drivers can give rise to acute megakaryoblastic leukaemia (AMKL), which arises within three clinical groups: children with Down syndrome, children without Down syndrome, and adults. Immunophenotyping and detection of markers of megakaryocytic differentiation are required to make a diagnosis of AMKL and detect the newly described “RAM immunophenotype”, which correlates with CBFA2T3 :: GLIS2 , a subtype of AML with other defined genetic alterations .

Myeloid sarcoma

Myeloid sarcoma represents a unique tissue-based manifestation of AML or transformed MDS, MDS/MPN, or MPN. Cases of de novo myeloid sarcoma should be investigated comprehensively, including cytogenetic and molecular studies, for appropriate classification and planning therapy. Molecular alterations in myeloid sarcoma and concurrent bone marrow disease are concordant in ~70% of patients, suggesting that myeloid sarcoma may be derived from a common haematopoietic stem cell or precursor [ 68 , 69 ]. Relevant gene mutations are detected in a subset of patients with morphologically normal-appearing bone marrow, suggesting low-level clonal myeloid disease or CH in the bone marrow [ 68 , 70 ].

AML is arranged into two families: AML with defining genetic abnormalities and AML defined by differentiation . AML, NOS is no longer applicable.

Most AML with defining genetic abnormalities may be diagnosed with <20% blasts.

AML-MR replaces the former term AML “with myelodysplasia-related changes”, and its diagnostic criteria are updated. AML transformation of MDS and MDS/MPN continues to be defined under AML-MR in view of the broader unifying biologic features.

AML with rare fusions are incorporated as subtypes under AML with other defined genetic alterations .

AML with somatic RUNX1 mutation is not recognized as a distinct disease type due to lack of sufficient unifying characteristics.

Secondary myeloid neoplasms

A newly segregated category encompassing diseases that arise in the setting of certain known predisposing factors.

Myeloid neoplasms that arise secondary to exposure to cytotoxic therapy or germline predisposition are grouped in this category. AML transformation of MPN is retained in the MPN category, while AML transformation of MDS and MDS/MPN is kept under AML-MR (see above). The framework of this disease category was redesigned with an eye towards two important areas: (1) providing a scalable structure for incorporating novel discoveries in the area of germline predisposition to myeloid neoplasia; (2) recognizing the dual importance of cataloguing myeloid neoplasms that arise following exposure to cytotoxic therapies for clinical purposes as well as population health purposes. The latter factor is gaining increased recognition as cancer survival is prolonged and the incidence of late complications of therapy such as secondary myeloid neoplasia increases. An overarching principle in this context is the requirement to consider “post cytotoxic therapy” and “associated with germline [gene] variant” as disease attributes that should be added as qualifiers to relevant myeloid disease types whose criteria are fulfilled as defined elsewhere in the classification, e.g. AML with KMT2A rearrangement post cytotoxic therapy or MDS with low blasts associated with germline RUNX1 variant .

Myeloid neoplasms post cytotoxic therapy: introduction of more precise terminology and novel associations with new cytotoxic drug classes

As in previous editions, this category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition. The terminology and definitions of this disease category have been modified slightly to reflect an improved understanding of the risk that CH plays as a risk factor for myeloid neoplasia related particularly to the expansion of pre-existing clones secondary to selection pressures of cytotoxic therapy agents in an altered marrow environment [ 71 ]. Thus, the diagnosis of myeloid neoplasms post cytotoxic therapy (MN-pCT) entails fulfilment of criteria for a myeloid neoplasm in addition to a documented history of chemotherapy treatment or large-field radiation therapy for an unrelated neoplasm [ 72 ]. This would exclude CCUS, which by definition lacks sufficient support for morphologic dysplasia. Cases with a ‘ de novo molecular signature’ such as NPM1 mutation and core-binding factor leukaemias should still be assigned to this category since the “ post cytotoxic therapy ” designation is based on the medical history, and the indication of the most specific diagnosis in the pathology report is recommended when possible. Exposure to PARP1 inhibitors is added as a qualifying criterion for MN-pCT, and methotrexate has been excluded. It is recommended that specification of the type of myeloid neoplasm is made when possible, with the appendix “post cytotoxic therapy” appended, e.g. CMML post cytotoxic therapy.

The majority of AML-pCT and MDS-pCT are associated with TP53 mutations. The outcomes of such patients are generally worse with biallelic (multi-hit) TP53 alterations, manifesting as ≥2 TP53 mutations, or with concomitant 17p/ TP53 deletion or copy neutral LOH. Less frequent mutations involve genes such as PPM1D and DNA-damage response genes that may require additional work-up for germline predisposition.

Myeloid neoplasms associated with germline predisposition: A novel scalable model is introduced

Myeloid neoplasms associated with germline predisposition include AML, MDS, MPN, and MDS/MPN that arise in individuals with genetic conditions associated with increased risk of myeloid malignancies. Myeloid neoplasms arising in individuals with Fanconi anemia, Down syndrome, and RASopathies are discussed in separate dedicated sections. These diseases are now classified using a formulaic approach that couples the myeloid disease phenotype with the predisposing germline genotype, e.g., AML with germline pathogenic variants in RUNX1 . The clinical manifestations of these diseases are grouped into three subtypes under which most germline predisposition conditions can be assigned. (Table  10 ) Genetic counseling and evaluation of family history is an expected component of the diagnostic evaluation of index patients. Myeloid proliferations associated with Down syndrome, typically associated with somatic exon 2 or 3 GATA1 mutation, continue to encompass two clonal conditions that arise in children with constitutional trisomy 21: transient abnormal myelopoiesis (TAM), which is confined to the first 6 months of life and myeloid leukaemia of Down syndrome (ML-DS).

Myeloid neoplasms (MDS, MDS/MPN, and AML) post cytotoxic therapy (MN-pCT) require full diagnostic work up; the term replaces therapy-related .

Exposure to PARP1 inhibitors is added as a qualifying criterion for MN-pCT.

The diagnostic framework for myeloid neoplasm associated with germline predisposition is restructured along a scalable model that can accommodate future refinement and discoveries.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are myeloid or lymphoid neoplasms driven by rearrangements involving genes encoding specific tyrosine kinases leading to fusion products in which the kinase domain is constitutively activated leading to cell signaling dysregulation that promotes proliferation and survival. (Table  11 ) These BCR::ABL1 -negative diseases have long been recognized in view of their distinctive clinicopathologic features and sensitivity to TKI. They encompass a broad range of histologic types, including MPN, MDS, MDS/MPN, AML, and MPAL, as well as B- or T- lymphoblastic leukaemia/lymphoma (ALL). Extramedullary disease is common. While eosinophilia is a common and salient feature, it may be absent in some cases. From a diagnostic hierarchy standpoint, the diagnosis of MLN-TK supersedes other myeloid and lymphoid types, as well as SM. In some instances, defining genetic abnormalities of MLN-TK are acquired during course of a myeloid neoplasm such as MDS or MDS/MPN or at the time of MPN BP transformation. MLN-TK must be excluded before a diagnosis of CEL is rendered.

The majority of MLN-TK cases associated with PDGFRA rearrangements have cytogenetically cryptic deletion of 4q12 resulting in FIP1L1 :: PDGFRA , but PDGFRA fusions involving other partners are also identified. Cases with PDGFRB rearrangement result most commonly from t(5;12)(q32;p13.2) leading to ETV6 :: PDGFRB ; however, more than 30 other partners have been identified. Cases with FGFR1 rearrangement may manifest as chronic myeloid neoplasms or blast-phase disease of B-cell, T-cell, myeloid or mixed-phenotype origin, typically with associated eosinophilia. The characteristic cytogenetic feature is an aberration of chromosome 8p11. Detection of JAK2 rearrangements leading to fusion products with genes other than PCM1 have been recognized, supporting MLN-TK with JAK2 rearrangement as a distinct type [ 73 , 74 ]. Cases with FLT3 fusion genes are particularly rare and result from rearrangements involving chromosome 13q12.2. They manifest as myeloid sarcoma with MPN features in the bone marrow or T-ALL with associated eosinophilia, but disease features and phenotypic presentation may be variable and diverse. MLN-TK with ETV6 :: ABL1 should be separated from B-ALL with ETV6 :: ABL1 [ 75 ].

The natural history of MLN-TK with PDGFRA or PDGFRB has been dramatically altered by TKI therapy, particularly imatinib. In contrast, patients with FGFR1 , JAK2 and FLT3 fusions and ETV6 :: ABL1 have more variable sensitivity to available newer generation TKIs [ 73 , 76 ]; in most cases, long-term disease-free survival may only be achievable with allogeneic haematopoietic stem cell transplantation.

Other less common defined genetic alterations involving tyrosine kinase genes have also been discovered, and these are listed as MLN-TK subtypes under MLN-TK with other defined tyrosine kinase fusions until further data is accrued [ 77 , 78 ].

Family renamed myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK).

Recognition of novel types with JAK2 rearrangements, FLT3 rearrangements, and ETV6 :: ABL1 fusion.

New scalable genetic framework introduced under MLN-TK with other defined tyrosine kinase fusions.

Acute leukaemias of mixed or ambiguous lineage

Acute leukemia of ambiguous lineage (ALAL) and mixed-phenotype acute leukaemia (MPAL) are grouped under a single category in view of their overlapping clinical and immunophenotypic features, which in recent studies have been shown to also share common molecular pathogenic mechanisms. Here too, a framework for a molecular classification is laid by separating ALAL/MPAL with defining genetic abnormalities from those that are defined based on immunophenotyping only. (Table  12 )

Two new subtypes of ALAL with defining genetic alterations are added. The first subtype is MPAL with ZNF384 rearrangement, which commonly has a B/myeloid immunophenotype and is identified in ~50% of pediatric B/myeloid MPAL with fusion partners including TCF3 , EP300 , TAF15 , and CREBBP. ZNF38 4-rearranged B/myeloid MPAL and B-ALL have similar transcriptional profile, suggesting a biological continuum [ 79 ]. The other subtype is ALAL with BCL11B rearrangement, which has a more heterogenous immunophenotype - identified in acute undifferentiated leukaemia (AUL) and ~20-30% of T/myeloid MPAL. BCL11B rearrangement is also identified in AML with minimal differentiation or without maturation and ~20-30% of ETP-ALL. [ 59 , 60 , 61 , 80 ] These different types of acute leukaemias with stem cell, myeloid, and T-ALL features having BCL11B rearrangement in common suggests a biological continuum. Other genomic findings such as PHF6 mutations and PICALM :: MLLT10 fusions are also enriched in MPAL, but more studies are needed.

The assignment of lineage by immunophenotyping is dependent on the strength of association between each antigen and the lineage being assessed. As a general principle, the closer the expression of an antigen is to either the intensity and/or pattern of expression seen on the most similar normal population, the more likely it reflects commitment to that lineage. For instance, variable myeloperoxidase expression with an intensity and pattern similar to that seen in early myeloid maturation is more strongly associated with myeloid lineage than uniform dim myeloperoxidase expression. In addition, demonstration of a coordinated pattern of expression of multiple antigens from the same lineage further improves the specificity of those antigens for lineage assignment, e.g. combined expression of CD19, CD22, and CD10 is more strongly associated with B lineage than each antigen individually. Given these principles, the immunophenotypic criteria to be used for lineage assignment in cases where a single lineage is not evident are revised. (Table  13 )

Assessment of myeloperoxidase expression by cytochemistry and/or flow cytometry immunophenotyping plays a key role intersecting AML with minimal differentiation, T/myeloid MPAL, and ETP-ALL. Various groups have proposed flow cytometry thresholds for positive myeloperoxidase expression in acute leukaemia, ranging from 3 to 28% of blasts [ 81 , 82 , 83 ]. The 3% cutoff for myeloperoxidase, historically used for cytochemistry, was determined to have high sensitivity but poor specificity for general lineage assignment in acute leukaemia by flow cytometry [ 82 , 83 ]. A threshold of >10% for myeloperoxidase positivity seems to improve specificity [ 81 ], but no consensus cutoff has been established.

Acute leukaemias of mixed or ambiguous lineage are arranged into two families: ALAL with defining genetic abnormalities and ALAL, immunophenotypically defined .

Novel genetic findings are listed as subtypes under ALAL with other defined genetic alterations as additional data accrues.

Lineage assignment criteria for MPAL are refined to emphasize principles of intensity and pattern.

Histiocytic/dendritic cell neoplasms

These neoplasms are positioned in the classification after myeloid neoplasms in recognition of their derivation from common myeloid progenitors that give rise to cells of the monocytic/histiocytic/dendritic lineages. (Table  14 ) Key changes in the current edition of the classification include: (1) inclusion of clonal plasmacytoid dendritic cell (pDC) diseases in this category; (2) moving follicular dendritic cell sarcoma and fibroblastic reticular cell tumor to a separate category; and, (3) addition of Rosai-Dorfman disease (RDD) and ALK-positive histiocytosis as disease types. Indeed, neoplasms that arise from lymphoid stromal cells such as follicular dendritic cell sarcoma and fibroblastic reticular cell tumor are now appropriately classified under the new chapter of “stroma-derived neoplasms of lymphoid tissues” as detailed in the companion manuscript [ 4 ].

Plasmacytoid dendritic cell neoplasms: recognition of clonal proliferations detected in association with myeloid neoplasms and refinement/update of the diagnostic criteria for blastic plasmacytoid dendritic cell neoplasm

Mature plasmacytoid dendritic cell proliferation (MPDCP) associated with myeloid neoplasm reflects recent data showing that these represent clonal proliferation of pDCs with low grade morphology identified in the context of a defined myeloid neoplasm. Clonal MPDCP cells accumulate in the bone marrow of patients with myeloproliferative CMML harbouring activating RAS pathway mutations [ 84 ]. Patients with AML can have clonally expanded pDCs (pDC-AML), which share the same mutational landscape as CD34 +  blasts, and frequently arise in association with RUNX1 mutations [ 85 , 86 ]. It is unknown whether the pathogenetic mechanisms leading to MPDCP in association with MDS or MDS/MPN and with AML are the same. The framework for diagnosing blastic plasmacytoid dendritic cell neoplasm remains largely the same, with emphasis on immunophenotypic diagnostic criteria. (Table  15 )

Dendritic and histiocytic neoplasms: Rosai-Dorfman disease and ALK-positive histiocytosis are new entities in the classification

Much has been learned about the molecular genetics of histiocytoses/histiocytic neoplasms in recent years. These neoplasms, in particular Langerhans cell histiocytosis/sarcoma, Erdheim-Chester disease, juvenile xanthogranuloma, RDD and histiocytic sarcoma, commonly show mutations in genes of the MAPK pathway, such as BRAF, ARAF, MAP2K1, NRAS and KRAS , albeit with highly variable frequencies, indicating a unifying genetic landscape for diverse histiocytoses and histiocytic neoplasms. ALK-positive histiocytosis furthermore converges on the MAPK pathway, which is one of the signaling pathways mediating ALK activation [ 87 , 88 ]. Insights on genetic alterations have significant treatment implications, because of availability of highly effective therapy targeting components of the activated signaling pathway, such as BRAF and MEK inhibitors [ 88 , 89 , 90 , 91 , 92 ].

For RDD, the distinctive clinicopathologic features with accumulation of characteristic S100-positive large histiocytes showing emperipolesis, coupled with frequent gain-of-function mutations in genes of the MAPK pathway indicating a neoplastic process, provides a rationale for this inclusion and offers opportunities for targeted therapy [ 92 , 93 , 94 , 95 ].

ALK-positive histiocytosis, which shows a broad clinicopathologic spectrum unified by the presence of ALK gene translocation (most commonly KIF5B :: ALK ) and remarkable response to ALK-inhibitor therapy, has been better characterized in recent studies [ 88 , 96 ]. The multisystem systemic form that typically occurs in infants, with involvement of liver, spleen and/or bone marrow, runs a protracted course but often resolves slowly, either spontaneously or with chemotherapy. Other multisystem and single-system cases occur in any age group, with involvement of two or more organs or one organ alone, respectively, most commonly central/peripheral nervous system and skin; the disease has a favourable outcome with systemic and/or surgical therapy [ 88 , 97 ]. The histiocytes in ALK-positive histiocytosis can assume variable appearances including large oval cells, foamy cells and spindle cells, some with multinucleation (including Touton giant cells) or emperipolesis. That is, morphology is not entirely diagnostic, and overlaps extensively with that of juvenile xanthogranuloma and rarely RDD. Thus, it is recommended that ALK immunostaining be performed for histiocytic proliferations not conforming to defined entities, to screen for possible ALK-positive histiocytosis.

In most circumstances, classification of a dendritic cell/macrophage neoplasm as Langerhans cell histiocytosis/sarcoma, indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma or histiocytic sarcoma is straightforward. Nonetheless, there are rare cases that show overlap or hybrid features, defying precise classification [ 98 , 99 ].

Among histiocytic neoplasms, a subset of cases occurs in association with or follow a preceding lymphoma/leukaemia, most commonly follicular lymphoma, chronic lymphocytic leukaemia and T- or B-ALL [ 100 ]. Since these histiocytic neoplasms usually exhibit the same clonal markers and/or hallmark genetic changes as the associated lymphoma/leukaemia, a “transdifferentiation” mechanism has been proposed to explain the phenomenon [ 99 , 100 , 101 ]. Furthermore, the histiocytic neoplasm and associated lymphoma/leukaemia often show additional genetic alterations exclusive to each component, suggesting that divergent differentiation or transdifferentiation occurs from a common lymphoid progenitor clone [ 100 , 102 , 103 ]. Histiocytoses are also sometimes associated with myeloproliferative neoplasms [ 104 ], sharing mutations with CD34 +  myeloid progenitors [ 105 ], and with CH [ 106 ].

Histiocytic/dendritic cell neoplasms are regrouped and positioned to follow myeloid neoplasms in the classification scheme in view of their close ontogenic derivation.

Mature pDC proliferation is redefined with an emphasis on recent data demonstrating shared clonality with underlying myeloid neoplasms. This framework is bound to evolve in future editions.

Diagnostic criteria of BPDCN are refined.

ALK-positive histiocytosis is introduced as a new entity.

Genetic tumor syndromes with predisposition to myeloid neoplasia

Fanconi anaemia is a heterogeneous disorder caused by germline variants in the BRCA-Fanconi DNA repair pathway (≥21 genes) resulting in chromosomal breakage and hypersensitivity to crosslinking agents used for diagnosis. Clinical features include congenital anomalies, bone marrow failure, and cancer predisposition [ 107 ]. The new classification distinguishes 5 haematologic categories depending on blast percentage, cytopenia and chromosomal abnormalities [ 108 ]. Dysgranulopoiesis and dysmegakaryopoiesis are histologic indicators of progression [ 109 ]. Allogenic haematopoietic stem cell transplantation is efficacious.

The term RASopathies encompasses a diverse group of complex, multi-system disorders associated with variants in genes involved in the RAS mitogen-activating protein kinase (MAPK) pathway. Myeloid neoplasms in RASopathies involve MAPK hyperactivation, leading to myeloid cell proliferation [ 110 ]. Genomic analysis of NF1 , NRAS , KRAS , PTPN11 , and CBL from myeloid neoplasms of patients suspected of having a RASopathy is important and aids in the diagnosis of JMML in the majority of cases [ 111 , 112 ]. Diagnostic criteria include pathogenic variants in genes associated with the RAS pathway and/or classic phenotype suggestive of a RASopathy [ 113 ].

The content of this article represents the personal views of the authors and does not represent the views of the authors’ employers and associated institutions. This work is intended to provide a preview and summary of content whose copyright belongs solely to the International Agency for Research on Cancer/World Health Organization. Any or all portions of the material in this work may appear in future International Agency for Research on Cancer/World Health Organization publications.

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Acknowledgements

We thank the leadership and staff of the International Agency for Research on Cancer (IARC), Lyon, France, especially Dr. Ian Cree and Ms. Asiedua Asante, for their tireless efforts.

The following colleagues are acknowledged for their expert contributions as authors in the WHO Classification of Haematolymphoid Tumours blue book on myeloid and histiocytic/dendritic cell topics:

Lionel Adès 53 , Iván Alvarez-Twose 54 , Lars Bullinger 55 , Andrey Bychkov 56 , Maria Calaminici 57 , Peter J Campbell 58 , Hélène Cavé 59 , Kenneth Tou En Chang 60 , Jorge E Cortes 61 , Immacolata Cozzolino 62 , Ian A Cree 63 , Sandeep S Dave 64 , Kara L Davis 65 , Rita De Vito 66 , Hans Joachim Deeg 67 , Elizabeth G. Demicco 68 , Ann-Kathrin Eisfeld 69 , Carlo Gambacorti-Passerini 70 , Francine Garnache Ottou 71 , Stephane Giraudier 72 , Lucy A Godley 73 , Peter L Greenberg 74 , Patricia T Greipp 75 , Alejandro Gru 76 , Sumeet Gujral 77 , Detlef Haase 78 , Claudia Haferlach 27 , Julien Haroche 79 , Xiao-Jun Huang 80 , Yin Pun Hung 22 , Ahmed Idbaih 81 , Masafumi Ito 82 , Thomas S Jacques 83 , Sidd Jaiswal 38 , Rhett P Ketterling 84 , Navin Khattry 85 , Rami S Komrokji 41 , Shinichi Makita 86 , Vikram Mathews 87 , L Jeffrey Medeiros 1 , Ruben Mesa 88 , Dragana Milojkovic 6 , Yasushi Miyazaki 89 , Valentina Nardi 22 , Gaurav Narula 86 , Seishi Ogawa 90 , Eduardo Olavarria 91 , Timothy S Olson 92 , Etan Orgel 93 , Sophie P Park 94 , Mrinal Patnaik 95 , Naveen Pemmaraju 31 , Mary-Elizabeth Percival 68 , Gordana Raca 94 , Jerald P Radich 96 , Sabrina Rossi 97 , Philippe Rousselot 98 , Felix Sahm 99 , David A Sallman 41 , Valentina Sangiorgio 100 , Marie Sebert 101 , Riccardo Soffietti 102 , Jamshid Sorouri Khorashad 103 , Karl Sotlar 104 , Karsten Spiekermann 105 , Papagudi Ganesan Subramanian 106 , Kengo Takeuchi 107 , Roberto Tirabosco 108 , Antonio Torrelo 109 , George S Vassiliou 110 , Huan-You Wang 111 , Bruce M Wenig 112 , David A Westerman 113 , David Wu 114 , Akihiko Yoshida 115 , Bernhard WH Zelger 116 , Maria Claudia Nogueira Zerbini 117

53 Hématologie Sénior Hôpital Saint Louis, and Université de Paris Cité, Paris, France. 54 Instituto de Estudios de Mastocitosis de Castilla La Mancha, CIBERONC, Hospital Virgen del Valle, Toledo, Spain. 55 Department of Hematology, Oncology and Tumor Immunology, Campus Virchow, Charité-Universitätsmedizin Berlin, Berlin, Germany. 56 Department of Pathology, Kameda Medical Center, Kamogawa, Chiba, Japan. 57 Department of Cellular Pathology, the Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. 58 Wellcome Sanger Institute, Hinxton, United Kingdom. 59 Institut de Recherche Saint-Louis, Paris University, Genetic Department, Molecular Genetic Unit, Robert Debré Hospital, Paris, France. 60 Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore. 61 Georgia Cancer Center, Augusta, GA, USA. 62 Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy. 63 International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France. 64 Duke Medical Center, Durham, NC, USA. 65 Department of Pediatrics, Center for Cancer Cellular Therapy, Cancer Correlative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA. 66 Department of Pathology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. 67 Clinical Research Division, Fred Hutchinson Cancer Center, Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA. 68 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 69 The Ohio State University, Columbus, OH, USA. 70 Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy. Hematology Division and Bone Marrow Unit, San Gerardo Hospital, ASST Monza, Monza, Italy. 71 Inserm UMR1098, Université de Franche-Comté, Laboratoire Hématologie, Etablissement Français du Sang Bourgogne Franche-Comté, Besançon, France. 72 Laboratoire UMRS-1131, Université de Paris, Hôpital Saint-Louis, Paris, France. 73 Section of Hematology/Oncology, Department of Medicine, Department of Human Genetics, The University of Chicago, Chicago, IL, USA. 74 Stanford Cancer Institute, Stanford, CA, USA. 75 Division of Laboratory of Genetics and Genomics, Mayo Clinic, Rochester, MN, USA. 76 Department of Pathology, E. Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA, USA. 77 Hematopathology Laboratory, Tata Memorial Center, Homi Bhabha National Institute, University, Mumbai, India. 78 Department of Hematology and Medical Oncology, University Medicine Göttingen, Göttingen, Germany. 79 Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service de Médicine Interne 2, Centre National de Référence des Histiocytoses, Hôpital Pitié-Salpêtrière, Paris, France. 80 Peking University People’s Hospital, Peking University Institute of Hematology, Peking University, Beijing, China. 81 Sorbonne Université, Institut du Cerveau—Paris Brain Institute—ICM, Hôpital Universitaire La Pitié Salpêtrière, DMU Neurosciences, Paris, France. 82 Department of Pathology, Japanese Red Cross, Aichi Medical Centre Nagoya Daiichi Hospital, Nagoya, Japan. 83 Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health; Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 84 Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 85 Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India. 86 Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. 87 Department of Hematology, Christian Medical College, Vellore, India. 88 Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, TX, USA. 89 Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 90 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden. 91 Servicio de Hematologia, Hospital de Navarra, Pamplona, Spain. 92 Department of Pediatrics, Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 93 Children’s Hospital Los Angeles; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 94 Centre Hospitalier Universitaire de Grenoble, Grenoble, France. 95 Mayo Clinic, Hematology Division, Rochester, MN, USA. 96 Department of Medicine, University of Washington, Seattle, WA, USA. 97 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom. 98 Centre Hospitalier de Versailles, Hematologie Oncologie, Le Chesnay, France. 99 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany. 100 Division of Hematopathology, Department of Cellular Pathology, The Royal London Hospital. Barts Health NHS Trust, London, United Kingdom. 101 3. Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique, Paris, France. 102 Division of Neuro-Oncology, Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy. 103 SIHMDS, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. 104 Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. 105 Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital. LMU Munich, Munich, Germany. 106 Hematopathology Laboratory, Tata Memorial Center, Homi Bhabha National Institute University, Navi Mumbai, Maharashtra, India. 107 Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. 108 Department of Histopathology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, United Kingdom. 109 Department of Dermatology, University Children’s Hospital Niño Jesús, Madrid, Spain. 110 University of Cambridge & Wellcome Sanger Institute, Cambridge, United Kingdom. 111 Division of Laboratory and Genomic Medicine, Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA. 112 Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA. 113 Department of Pathology, Peter MacCallum Cancer Centre, Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville; Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia. 114 Department of Laboratory Medicine and Pathology, School of Medicine, Seattle, WA, USA. 115 Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan. 116 Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria. 117 Faculdade de Medicina, Universidade de São Paulo, Departamento de Patologia, São Paulo, Brazil.

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Joseph D. Khoury, Shimin Hu, Rashmi Kanagal-Shamanna, Sanam Loghavi, Keyur P. Patel & Wei Wang

Department of Hematology, Gustave Roussy Cancer Center, Université Paris-Saclay, Villejuif, France

Eric Solary

Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada

Oussama Abla

The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

Yassmine Akkari

Pathology Unit, Department of Laboratories, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy

Rita Alaggio

Centre for Haematology, Imperial College London, London, UK

Jane F. Apperley

Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

Rafael Bejar

University of Milan, Fondazione Cà Granda, IRCCS, Ospedale Maggiore Policlinico, Milano, Italy

Emilio Berti

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Lambert Busque

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John K. C. Chan

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Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

Xueyan Chen

Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore

Wee-Joo Chng

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John K. Choi

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Isabel Colmenero

Liverpool Clinical Laboratories, Liverpool University Hospitals Foundation Trust, Liverpool, UK

Sarah E. Coupland

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Nicholas C. P. Cross

Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam, The Netherlands

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Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

Linda Fogelstrand

Laboratory of Hematology, Assistance Publique-Hôpitaux de Paris, Cochin Hospital and Université Paris Cité, CNRS, INSERM, Cochin Institute, Paris, France

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MLL Munich Leukemia Laboratory, Munich, Germany

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Claire Harrison

Indiana University School of Medicine, Indianapolis, IN, USA

Jennelle C. Hodge

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Joop H. Jansen

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Hagop M. Kantarjian & Srdan Verstovsek

Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

Christian P. Kratz

Departments of Pathology and Oncology, Fudan University, Shanghai, China

Xiao-Qiu Li

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

Megan S. Lim

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Keith Loeb, Kikkeri N. Naresh & Cecilia Yeung

Pediatric Hematology and Oncology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Soheil Meshinchi

Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

Phillip Michaels

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Yasodha Natkunam

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Reza Nejati

Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Eric Padron

Hematopathology Laboratory, Tata Memorial Hospital, Mumbai, India

Nikhil Patkar & Prashant Tembhare

Pathology and Lab Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Jennifer Picarsic

Department of Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

Uwe Platzbecker

Department of Paediatrics, University of Oxford, Oxford, UK

Irene Roberts

Department of Oncology, University of Oxford, Oxford, UK

Immunology Division, Garvan Institute of Medical Research, Sydney, Australia

William Sewell

Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany

Reiner Siebert

Cell, Developmental & Cancer Biology Department, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

Jeffrey Tyner

Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

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Wenbin Xiao

Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany

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JDK and JCH are standing members of the WHO Classification of Tumours editorial board. ES, YA, RA, JKCC, WJC, SEC, DDJ, JF, SG, HMK, MSL, KNN, GO, AS, WS, RS, BW and AH are expert members of the Haematolymphoid Tumours 5th edition blue book editorial board. OA, JFA, RB, EB, LB, WC, XC, JKC, IC, NCPC, MTE, ET, JFE, LF, MF, UG, TH, CH, SH, JHJ, RKS, CPK, XQL, KL, SL, AM, SM, PM, YN, RN, EP, KPP, NP, JP, UP, IR, PT, JT, SV, WW, WX, and CY contributed as responsible authors in the book. All authors and editors contributed to discussions on the content of the book chapters. All listed authors edited and approved the manuscript.

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Khoury, J.D., Solary, E., Abla, O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36 , 1703–1719 (2022). https://doi.org/10.1038/s41375-022-01613-1

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World Health Organization (WHO)

• 09 Jul 2019
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Last Updated: July 2022

World Health Organization (WHO), the United Nations’ specialized agency for Health was founded in 1948.

• Its headquarters are situated in Geneva, Switzerland.
• There are 194 Member States, 150 country offices, six regional offices.
• It is an inter-governmental organization and works in collaboration with its member states usually through the Ministries of Health.
• The WHO provides leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends.
• It began functioning on April 7, 1948 – a date now being celebrated every year as World Health Day .

What are the Objectives?

• To act as the directing and coordinating authority on international health work.
• To establish and maintain effective collaboration with the United Nations, specialized agencies, governmental health administrations, professional groups and such other organizations as may be deemed appropriate.
• To provide assistance to the Governments, upon request, in strengthening health services.
• To promote cooperation among scientific and professional groups which contribute to the advancement of health.

How is it Governed?

World health assembly.

• World Health Assembly (WHA) is WHO’s decision-making body attended by delegations from all of WHO’s member states,
• It is held yearly at the headquarters of WHO, i.e., Geneva, Switzerland.
• Specific health agenda prepared by the Executive Board remains the focus of this assembly.
• Since the start of the Covid-19 pandemic, 2022’s assembly is the first in-person assembly.
• In May 2022, World Health Assembly’s 75 th session was held at World Health Organization (WHO).
• The Health Assembly determines the policies of the Organization.
• It supervises the financial policies of the Organization and reviews and approves the budget.
• It reports to the Economic and Social Council in accordance with any agreement between the Organization and the United Nations.

The Secretariat

• The Secretariat comprises of the Director-General and such technical and administrative staff as the Organization may require.
• The Director-General is appointed by the Health Assembly on the nomination of the Board on such terms as the Health Assembly may determine.

Membership and Associate Membership

• Members of the United Nations may become Members of the Organization.
• Territories or groups of territories which are not responsible for the conduct of their international relations may be admitted as Associate Members by the Health Assembly.

What are the contributions of WHO to the world?  

• They provide technical support on health matters, share relevant global standards and guidelines, and relay government requests and requirements to other levels of WHO.
• They also inform and follow up with the host government on reports of disease outbreaks outside the country.
• They provide advice and guidance on public health to other UN agency offices in-country.
• In addition to governments, WHO also coordinates with other UN agencies, donors, non-governmental organizations (NGOs) and the private sector.
• For example, all nations have benefited from their contributions to the WHO programs that led to the global eradication of smallpox and to promote better and cheaper ways of controlling tuberculosis.
• WHO is leading a worldwide campaign to provide effective immunization for all children in cooperation with the United Nations Children’s Fund (UNICEF).
• These included malaria, yaws, tuberculosis, and venereal diseases.
• There was also a high priority for maternal and child health services, for environmental sanitation (especially safe water), and for standardization of drugs and vaccines.
• In these years, WHO developed close working relationships with other UN agencies.
• Working with the international Red Cross , WHO recruited 200 physicians and other health workers, and established a new fellowship program to enable scores of Congolese “medical assistants” to become fully qualified doctors.
• In this period, fellowships for health-personnel development became a major WHO strategy in almost all countries.
• WHO stimulated and even collaborated with the world chemical industry in the 1960s to develop new insecticides for fighting the vectors of onchocerciasis (“river blindness”) and for treating schistosomiasis.
• Demonstration that tuberculosis could be effectively treated, without expensive sanatorium care, was a great breakthrough of the late 1950s.
• Even the mundane standardization of the nomenclature of diseases and causes of death was an important contribution of WHO to international health communications.
• In 1967, smallpox was still endemic in thirty-one countries, afflicting between 10 and 15 million people.
• The work was done by teams of public health workers in all the countries affected, with WHO serving as leader, co-ordinator, and inspiration.
• Millions of dollars were saved worldwide by this achievement, which overcame various national rivalries and suspicions.
• The momentum of this great campaign added strength to another drive, for expanding the immunization of the world’s children against six once-ravaging diseases: diphtheria, tetanus, whooping cough, measles, poliomyelitis, and tuberculosis (with BCG vaccine).
• After long hesitation for political reasons, in this period WHO finally entered the field of family planning by promoting worldwide research and development on human reproduction.
• New efforts were also put into the control of malaria and leprosy.
• Such training was a sounder investment in most developing countries than preparing physicians for predominantly urban medical practice.
• This approach, stressing community participation, appropriate technology, and intersectoral collaboration, became the central pillar of world health policy.
• Thirty years after its birth, 134 WHO member-states reaffirmed their commitment to equality, as embodied in the slogan “Health for All.”
• The provisions of the safe drinking water and adequate excreta disposal for all were the objectives of the International Drinking Water Supply and Sanitation Decade (1981-90) proclaimed by the UN General Assembly in 1980 and supported by WHO.
• In this period, every country was encouraged to develop a list of “essential drugs” for use in all public facilities, instead of the thousands of brand-name products sold in world markets.
• The WHO’s condemnation of the promotion of artificial infant-formula products in developing countries also attracted widespread attention.
• The worldwide control of infantile diarrhea with oral rehydration therapy was another great advance, based on very simple principles.
• So in 1997, WHO (in collaboration with Canada) rolled out the Global Public Health Intelligence Network (GPHIN), which took advantage of information on the Internet to function as an early warning system for potential epidemics.
• GOARN linked 120 networks and institutes with the data, laboratories, skills and experience to take action swiftly in a crisis.
• According to the WHO, most of the estimated 500000 maternal deaths each year are preventable through family planning —to avoid illegal abortions—and hygienic education of traditional birth-attendants.
• The WHO has also mounted increasing efforts against cancer, which now takes as many lives in the developing countries as in the affluent ones.
• The fight against tobacco, the largest single cause of preventable death in both men and women, is part of WHO effort in every country.
• Disseminating the simple rules of diet, exercise, nonsmoking, prudent use of alcohol, and hygienic working conditions are major objectives of health education in WHO everywhere.
• The WHO is working for the introduction of self-testing so that more people living with HIV know their status and can receive treatment.
• The World Health Organisation (WHO) characterised Covid-19 as a pandemic in 2021.

According to the WHO, a pandemic is declared when a new disease for which people do not have immunity spreads around the world beyond expectations.

On the other hand, an epidemic is a large outbreak, one that spreads among a population or region. It is less severe than pandemic due to a limited area of spread.

WHO and India: What is the Scenario?

• India became a party to the WHO on 12 January 1948.
• Regional office for South East Asia is located in New Delhi.
• In 1967 the total number of smallpox cases recorded in India accounted for nearly 65% of all cases in the world. Of this 26,225 cases died, giving a grim picture of the relentless fight that lay ahead.
• In 1967, the WHO launched the Intensified Smallpox Eradication Programme.
• With a coordinated effort by Indian government with the World Health Organization (WHO), smallpox was eradicated in 1977.
• India began the battle against the disease in response to the WHO’s 1988 Global Polio Eradication Initiative with financial and technical help from World Bank.
• Polio Campaign-2012: The Indian Government, in partnership with UNICEF, the World Health Organization (WHO), the Bill & Melinda Gates Foundation, Rotary International and the Centers for Disease Control and Prevention contributed to almost universal awareness of the need to vaccinate all children under five against polio.
• As a result of these efforts, India was removed from the list of endemic countries in 2014.
• Recently, the Prime Minister addressed the Second Global Covid Virtual Summit of the World Health Organisation (WHO) , where he emphasized WHO Reforms.

What are the Reforms Suggested by India?

• It is important to devise objective criteria with clear parameters for declaring PHEIC.
• The emphasis must be on transparency and pr omptness in the declaration process.
• Serious, sudden, unusual or unexpected;
• Carries implications for public health beyond the affected State’s national border; and
• May require immediate international action.
• Most of the financing for Programmatic Activities of the WHO comes from extra budgetary contributions, which though voluntary in nature, are normally earmarked. The WHO enjoys very little flexibility in the use of these funds.
• There is a need to ensure that extra budgetary or voluntary contributions are unearmarked to ensure that the WHO has the necessary flexibility for its usage in areas where they are required the most.
• There is no collaborative mechanism wherein the actual projects and activities are decided in consultation with member states, there is no review with respect to value for money and whether projects are being done as per the member states priorities or if there are abnormal delays.
• It is also crucial to establish a significant amount of transparency with respect to data reporting and disbursement of funds for increased accountability.
• Implementation of the IHR 2005 has highlighted critical gaps in the basic health infrastructure of member States. This has become more evident in their dealing with COVID 19 pandemic.
• It is important that the programmatic activities carried out by the WHO, under its General Programme of Work, should focus on building and strengthening capacities in member states as required under IHR 2005, which are found lacking or deficient on the basis of the self-reporting on IHR 2005 done by the Member States.
• Being a technical Organisation, most of the work in WHO is done in Technical Committees composed of independent experts. Moreover, considering the growing risks associated with emergence of disease outbreaks the role of the Independent Oversight and Advisory Committee (IOAC), responsible for the performance of the WHO Health Emergencies Programme (WHE), becomes extremely crucial.
• It is important that the member States have a greater say in the functioning of the WHO , given that it is the States which are responsible for implementation on ground of the technical advice and recommendations coming from the WHO.
• There is a need to devise specific mechanisms like a Standing Committee of the Executive Board to ensure effective supervision by member States.
• IHR (2005), represents a binding international legal agreement involving 196 countries across the globe, including all the Member States of the WHO.
• Their aim is to help the international community prevent and respond to acute public health risks that have the potential to cross borders and threaten people worldwide.
• The review of the IHR implementation should continue to be on a voluntary basis.
• It is critical to accord priority to enhance international cooperation, which should be directed at aiding developing countries in areas which they have been identified as lacking the necessary capacity to implement the IHR.
• It has been felt that the TRIPS flexibilities provided for public health, under Doha Declaration, may not be sufficient to deal with crises such as Covid-19 pandemic.
• It is important to ensure fair, affordable, and equitable access to all tools for combating Covid-19 pandemic and, therefore, the need to build a framework for their allocation.
• There is a need to create a monitoring mechanism and support to member states on International Health Regulations, preparedness of infrastructure, human resources and relevant health systems capacities such as testing and surveillance systems.
• Enhancement of capacities of countries in preparation for and response to infectious diseases of pandemic potential, including guidance on effective public health and economic measures for health emergencies by leveraging a multidisciplinary approach which includes social science alongside health and natural sciences.
• The risks imposed on humankind, by new influenza viruses causing more disease outbreaks are very real.
• There is an urgent need for the global community to address this issue by making bold efforts and ensuring vigilance and preparedness in our healthcare systems.
• The primary objective should be to improve capacity for global pandemic prevention, preparedness, and response, and strengthening our ability to fight back any such pandemic in future.

What is the role of WHO in World Health Concerns?

• Nine out of ten people breathe polluted air every day. In 2019, air pollution is considered by the WHO as the greatest environmental risk to health.
• Microscopic pollutants in the air can penetrate respiratory and circulatory systems, damaging the lungs, heart and brain, killing 7 million people prematurely every year from diseases such as cancer, stroke, heart and lung disease.
• Between 2030 and 2050, climate change is expected to cause 250 000 additional deaths per year, from malnutrition, malaria, diarrhoea and heat stress.
• Noncommunicable diseases, such as diabetes, cancer and heart disease, are collectively responsible for over 70% of all deaths worldwide, or 41 million people.
• The rise of these diseases has been driven by five major risk factors: tobacco use, physical inactivity, the harmful use of alcohol, unhealthy diets and air pollution.
• These risk factors also exacerbate mental health issues. The suicide is the second leading cause of death among 15-19 year-olds.
• The WHO is constantly monitoring the circulation of influenza viruses to detect potential pandemic strains: 153 institutions in 114 countries are involved in global surveillance and response.
• More than 1.6 billion people (22% of the global population) live in places where protracted crises (through a combination of challenges such as drought, famine, conflict, and population displacement) and weak health services leave them without access to basic care.
• It is the ability of bacteria, parasites, viruses and fungi to resist modern medicines which threatens to send us back to a time when we were unable to easily treat infections such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis.
• The inability to prevent infections could seriously compromise surgery and procedures such as chemotherapy.
• In 2017, around 600 000 cases of tuberculosis were resistant to rifampicin – the most effective first-line drugs – and 82% of these people had multidrug-resistant tuberculosis.
• Drug resistance is driven by the overuse of antimicrobials in people, but also in animals, especially those used for food production, as well as in the environment.
• WHO is working with these sectors to implement a global action plan to tackle antimicrobial resistance by increasing awareness and knowledge, reducing infection, and encouraging prudent use of antimicrobials.
• In 2018, the Democratic Republic of the Congo saw two separate Ebola outbreaks, both of which spread to cities of more than 1 million people. One of the affected provinces is also in an active conflict zone.
• This watchlist for priority research and development includes Ebola, several other haemorrhagic fevers, Zika, Nipah, Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS) and disease X, which represents the need to prepare for an unknown pathogen that could cause a serious epidemic.
• Primary health care is usually the first point of contact people have with their health care system, and ideally should provide comprehensive, affordable, community-based care throughout life.
• Yet many countries do not have adequate primary health care facilities. This neglect may be a lack of resources in low- or middle-income countries, but possibly also a focus in the past few decades on single disease programmes.
• It is the reluctance or refusal to vaccinate despite the availability of vaccines – threatens to reverse progress made in tackling vaccine-preventable diseases.
• Measles, for example, has seen a 30% increase in cases globally. The reasons for this rise are complex, and not all of these cases are due to vaccine hesitancy.
• However, some countries that were close to eliminating the disease have seen a resurgence.
• The WHO has identified complacency, inconvenience in accessing vaccines, and lack of confidence as key reasons underlying hesitancy.
• It is a mosquito-borne disease that causes flu-like symptoms and can be lethal and kill up to 20% of those with severe dengue, has been a growing threat for decades.
• A high number of cases occur in the rainy seasons of countries such as Bangladesh and India.
• WHO’s Dengue control strategy aims to reduce deaths by 50% by 2020.
• The progress made against HIV has been enormous in terms of getting people tested, providing them with antiretrovirals (22 million are on treatment), and providing access to preventive measures such as a pre-exposure prophylaxis (PrEP, which is when people at risk of HIV take antiretrovirals to prevent infection).
• Today, around 37 million worldwide live with HIV.
• Reaching people like sex workers, people in prison, men who have sex with men, or transgender people is hugely challenging. Often these groups are excluded from health services.
• A group increasingly affected by HIV are young girls and women (aged 15–24), who are particularly at high risk and account for 1 in 4 HIV infections in sub-Saharan Africa despite being only 10% of the population.
• The WHO is working with countries to support the introduction of self-testing so that more people living with HIV know their status and can receive treatment (or preventive measures in the case of a negative test result).
• The WHO characterised Covid-19 as a pandemic in 2021.
• Subsequently, the disease spread to more provinces of China and to the rest of the world, with the WHO declaring it a global health emergency. The virus has been named SARS-CoV-2 and the disease is now called COVID-19.
• If that is positive, the sample is sent to the National Institute of Virology in Pune, which is the only government laboratory currently doing genome sequencing, for final confirmation.
• The virus has spread to “non-endemic countries”. This virus has spread rapidly to many countries that have not seen it before.
• Monkeypox is a viral zoonotic disease with symptoms similar to smallpox, although with less clinical severity.
• The infection was first discovered in 1958 following two outbreaks of a pox-like disease in colonies of monkeys kept for research — which led to the name ‘monkeypox’.

What are the WHOs' Organisational Challenges?

• As a result, currently 80% of WHO’s funding is tied to programs that donors choose. Work programs that are vital to WHO’s mandate remain under funded as they clash with the interests of big donors, especially of rich and developed countries.
• Consequently WHO’s role as a leader in global health has been supplanted by other intergovernmental bodies such as the World Bank, and increasingly by big foundations.
• The organisation’s efficacy has come under question, especially after its inadequate performance in containing West Africa’s ebola epidemic of 2014.
• It was because of WHO's insufficient funding, structuring, staffing and bureaucracy.

World Health Organization

The World Health Organization (WHO) is a specialized agency of the United Nations (UN) that is concerned with international public health. It was established on 7 April 1948, with its headquarters in Geneva, Switzerland. WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations. WHO is responsible for the  World Health Report , a leading international publication on health, the worldwide World Health Survey, and World Health Day (7th-April of every Year).

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World Health Organization review finds 'no association' between mobile phone use or radio wave exposure and brain cancer

By Brianna Morris-Grant

Topic: Health

Researchers commissioned by the World Health Organization have found no evidence showing mobile phone use causes brain cancer.  ( Pexels: Adrienn )

Research commissioned by the World Health Organization has found no link between mobile phone use and brain cancer.

Radio waves associated with phone use have previously been classified as a possible carcinogen. 

What's next? 

The researchers involved with the study say the results are "reassuring" and previous studies had relied on the limited evidence available. 

There is no association between mobile phone use and brain cancer, a systematic review into radio wave exposure has found.

The review, commissioned by the World Health Organization (WHO), looked at thousands of studies published between 1994-2022.

Ultimately only 63 were found to be relevant.

The lead researcher was Ken Karipidis, the Health Impact Assessment assistant director of the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) and Vice-Chair of the International Commission of Non-Ionizing Radiation Protection (ICNIRP).

He said health officials had first classified radio wave exposure as a "possible" carcinogen in 2013.

"Many members of the public were very concerned," he said, but noted it was based on the limited evidence available at the time.

"Our systematic review … is the most comprehensive review to date.

"What we concluded was that the evidence does not show a link between mobile phone use and brain cancer, or other head and neck cancers.

"We also found no association with prolonged use, so if people use their phone for 10 years or more.

"We also found no association with the amount of mobile phone use, either the number of calls that people make or the amount of time they spent on the phone."

Researchers also found no association between other types of radio waves, like those from mobile phone towers, or workplace radio wave exposure, and any type of cancer.

People working in a range of industries, including broadcast telecommunications, medicine, and welding, could potentially be exposed to higher levels of radio waves.

The WHO’s International Agency for Research on Cancer (IARC) classified “radiofrequency electromagnetic fields” associated with mobile phone use as possibly carcinogenic in 2011. 

Their statement at the time noted evidence was both limited and inadequate, but sufficient to conclude there “could be some risk”. 

Dr Karipidis said everyday exposure to radio waves was "extremely low", but that mobile phones were the biggest exposure.

"Anything that uses wireless technology to communicate uses radio waves," he said.

"So wherever you're sitting at the moment, you're exposed to a variety of different radio waves.

"Apart from your mobile phone, you've got wireless laptops, there's also mobile phone towers outside your house, there's mobile TV transmissions, so we're always exposed to low-level radio waves in our everyday environment.

"Because people hear the word 'radiation' … and because we use a mobile phone close to the head during calls, there has been a lot of concern.

"We believe that's quite reassuring for this long-standing issue."

The WHO study aligned with previous ARPANSA research in 2019, which found overall brain tumour rates had remained stable during a time period with "substantial mobile phone use" in 2003-2013.

The 2019 research found there had been no increase in any kind of brain tumour that could be linked to mobile phones in Australia.

Asked whether IARC should consider reviewing its classification, Dr Karipidis said the carcinogen label "didn't mean much".

"To give you an example, aloe vera is classified as a possible carcinogen, talcum powder is a possible carcinogen," he said.

"It doesn't mean all that much.

"Having said that, the classification itself was quite controversial … there is some chatter that that might happen."

WHO issues guideline to curb antibiotic pollution

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• Copy URL https://www.pbs.org/newshour/world/first-batch-of-mpox-vaccines-arrive-in-congo-as-health-officials-say-3-million-doses-needed

First batch of mpox vaccines arrive in Congo as health officials say 3 million doses needed

KINSHASA, Congo (AP) — The first batch of mpox vaccine arrived in Congo’s capital on Thursday, the country’s authorities said, three weeks after the World Health Organization declared mpox outbreaks in 12 African countries a global emergency.

The 100,000 doses of the MVA-BN vaccine, manufactured by the Danish company Bavarian Nordic, have been donated by the European Union through HERA, the bloc’s agency for health emergencies. Another 100,000 are expected to be delivered on Saturday, the Congolese authorities said.

WATCH:  Epidemiologist breaks down how and where mpox is spreading

UNICEF is going to be in charge of the vaccination campaign in the most impacted provinces, Congo’s Health Minister Roger Kamba told reporters after the delivery of the vaccine. But it remained unclear when the vaccination drive would begin.

About 380,000 doses of mpox vaccines have been promised by Western partners such as the European Union and the United States, Dr. Jean Kaseya, head of the Africa Centers for Disease Control and Prevention, told reporters last week. That is less than 15% of the 3 million doses authorities have said are needed to end the mpox outbreaks in Congo, the epicenter of the global health emergency.

Mpox, also known as monkeypox, had been spreading mostly undetected for years in Africa before the disease prompted the 2022 outbreak in more than 70 countries, Dr. Dimie Ogoina, the chair of WHO’s mpox emergency committee told reporters last month.

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Global Health

No Vaccines, Tests or Treatments: Congo Lacks Tools to Confront Mpox

The country at the center of a global health emergency is struggling even to diagnose cases and provide basic care.

• Share full article

By Stephanie Nolen

Stephanie Nolen covered the 2022 mpox outbreak and has reported on health crises from the Democratic Republic of Congo.

Health officials in the Democratic Republic of Congo, the epicenter of a shape-shifting mpox outbreak, say they lack even the most basic tools necessary to contain and treat the virus.

The country has limited capacity to diagnose cases of mpox, even as transmission and the presentation of the disease are changing. That is complicating efforts to trace contacts and establish the true scale and spread of the outbreak.

There is no effective antiviral treatment for mpox in Congo. The country is also short on the medications necessary to treat people with painful mpox lesions. Its fragile public health system is struggling to provide those infected with basic care, which has been shown to improve survival rates even in the absence of antiviral drugs.

And the country is still waiting for vaccines to begin a campaign to protect health workers and close contacts of those infected and to try to check spread of the virus.

“We thought when there was an emergency declaration from the World Health Organization in 2022 that then we would get help with surveillance and really understanding this disease,” said Dr. Jean-Jacques Muyembe-Tamfum, the director of the National Institute of Biomedical Research in Kinshasa.

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First phase of polio campaign concludes successfully in Gaza

Over 187 000 children under ten years of age were vaccinated with novel oral polio vaccine type 2 (nOPV2) in central Gaza during the first phase of a two-round polio vaccination campaign, conducted between 1–3 September 2024. Vaccination coverage in this phase exceeded the initial estimated target of 157 000 children due to population movement towards central Gaza, and expanded coverage in areas outside the humanitarian pause zone.  

To ensure no child is missed in this area, polio vaccination will continue at four large health facilities in central Gaza over the next few days. Vaccine doses have been supplied to these sites to meet any additional needs. 

“It has been extremely encouraging to see thousands of children being able to access polio vaccines, with the support of their resilient families and courageous health workers, despite the deplorable conditions they have braved over the last 11 months. All parties respected the humanitarian pause and we hope to see this positive momentum continue,” said Dr Richard Peeperkorn, WHO Representative for the occupied Palestinian territory.

The first phase of the campaign was conducted by 513 teams, consisting of over 2180 health and community outreach workers. Vaccination was provided at 143 fixed sites, including hospitals, medical points, primary care centres, camps where displaced people are living, key public gathering spaces such as temporary learning spaces, food and water distribution points, and transit routes leading from central towards northern and southern Gaza. Additionally, mobile teams visited tents and hard to-reach areas to ensure they reached families who were unable to visit fixed sites. The presence of a substantial number of children eligible for vaccination who were unable to reach vaccination sites due to insecurity, necessitated special missions to Al-Maghazi, Al-Bureij and Al-Mussader – areas just outside of the agreed zone for the humanitarian pause.  

Preparations are underway to roll out the next phase of the campaign, which will be conducted in southern Gaza from 5–8 September 2024, targeting an estimated 340 000 children below ten years of age. Some 517 teams, including 384 mobile teams, will be deployed. Nearly 300 community outreach workers have already begun outreach to families in southern Gaza to raise awareness about the campaign, while 490 vaccine carriers, 90 cold storage boxes, and other supplies have been transferred to Khan Younis for distribution to vaccination sites. 

The third and last phase of the polio vaccination campaign will be implemented in northern Gaza from 9–11 September 2024, targeting around 150 000 children.  

At least 90% vaccination coverage during each round of the campaign is needed to stop the outbreak, prevent the international spread of polio and reduce the risk of its re-emergence, given the severely disrupted health, water and sanitation systems in the Gaza Strip. Vaccination coverage will be monitored throughout the campaign, and, when necessary, vaccinations will be extended to meet coverage targets as part of flexible strategies to ensure every eligible child receives their vaccine dose. 

The two-round campaign, being conducted by the Palestinian Ministry of Health (MOH), in collaboration with the World Health Organization (WHO) and United Nations Children Fund (UNICEF), the United Nations Relief and Works Agency for Palestine Refugees (UNRWA) and many partners, aims to provide two drops of nOPV2 to around 640 000 children during each round. 

"The successful delivery of the first phase of the campaign in central Gaza is a culmination of immense coordination among various partners, including the Global Polio Eradication Initiative (GPEI) and donors, and underscores the importance of peace for the health and well-being of people in Gaza. We call on all parties to continue fulfilling their commitment to the humanitarian pauses as the second phase of the campaign begins tomorrow,” said Dr Peeperkorn. 

Notes to editors  

• The campaign is part of an urgent response to prevent the spread of polio after circulating variant poliovirus type 2 (cVDPV2) was detected in Gaza, after 25 years of being polio-free. cVDPV2 has been detected in six environmental samples – or wastewater – collected from central Gaza in June 2024. Gaza has reported four cases of children with acute flaccid paralysis (AFP), including one case of confirmed polio in a child who tested positive for circulating variant poliovirus type 2 (cVDPV2). Two of the reported cases tested negative for poliovirus. Laboratory results are pending on samples from the fourth AFP case.  
• Novel oral polio vaccine (nOPV2) is a polio vaccine being used to stop transmission of variant poliovirus type 2 (cVDPV2), currently the most prevalent form of the variant poliovirus. 
• nOPV2 is safe and effective and offers protection against paralysis and community transmission. It is the vaccine globally recommended for variant type 2 poliovirus outbreaks – the type that has been found in the recent samples from Gaza. 

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