| Acute myeloid leukemia | |
|---|---|
| Other names | Acute myelogenous leukemia, acute nonlymphocytic leukemia (ANLL), acute myeloblastic leukemia, acute granulocytic leukemia[1] |
.jpg) | |
| Acute myeloid leukemia. In the cytoplasm of individual cells, characteristic inclusions –Auer rods – are visible. | |
| Specialty | Hematology,oncology |
| Symptoms | Feeling tired,shortness of breath, easy bruising and bleeding, increased risk ofinfection[1] |
| Usual onset | 65–70 years old |
| Risk factors | Smoking, previouschemotherapy orradiation therapy,myelodysplastic syndrome,benzene[1] |
| Diagnostic method | Bone marrow aspiration,blood test[2] |
| Treatment | Chemotherapy,radiation therapy,stem cell transplant,Targeted inhibitors[1][2] |
| Prognosis | Five-year survival ~33% (US, 2015–2021)[3] |
| Frequency | 145,000 per year (2021) |
| Deaths | 130,000 (2021) |
Acute myeloid leukemia (AML) is acancer of themyeloid line ofblood cells, characterized by the rapid growth of abnormal cells that build up in thebone marrow andblood and interfere withnormal blood cell production.[1] Symptoms may includefeeling tired,shortness of breath,easy bruising,bleeding, and increased risk ofinfection.[1] Occasionally, spread may occur to thebrain,skin, orgums.[1] As anacute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.[1]
Risk factors include getting older, being male,[4]smoking, previouschemotherapy orradiation therapy,myelodysplastic syndrome, and exposure to the chemicalbenzene.[1] The underlying mechanism involves replacement of normal bone marrow withleukemia cells, which results in adrop in red blood cells,platelets, and normalwhite blood cells.[1] Diagnosis is generally based onbone marrow aspiration and specificblood tests.[2] AML has several subtypes for which treatments and outcomes may vary.[1]
The first-line treatment of AML is usuallychemotherapy, with the aim of inducingremission.[1] People may then go on to receive additional chemotherapy, radiation therapy, or astem cell transplant.[1][2] The specificgenetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive.[2]
Between 2017 and 2025, 12 new agents have been approved for AML in the U.S., including venetoclax (BCL2 inhibitor), gemtuzumab ozogamicin (CD33 antibody-drug conjugate), and several inhibitors targeting FMS-like tyrosine kinase 3, isocitrate dehydrogenase, and other pathways. Additionally, therapies like CPX351 and oral formulations of azacitidine and decitabine-cedazuridine have been introduced. Ongoing research is exploring menin inhibitors and other antibody-drug conjugates.[5]
Low-intensity treatment with azacitidine plus venetoclax[6] has emerged as the most effective option for older or unfit AML patients, based on a network meta-analysis of 26 trials involving 4,920 participants. It showed the highest survival and remission rates, with low-dose cytarabine (LDAC) plus glasdegib and LDAC plus venetoclax also showing clinical benefit.[7]
In 2015, AML affected about one million people, and resulted in 147,000 deaths globally.[8][9] It most commonly occurs in older adults.[3] Males are affected more often than females.[3] As of 2015[update], the five-year survival rate was about 35% in people under 60 years old and 10% in people over 60 years old.[2] Older people whose health is too poor for intensive chemotherapy have atypical survival of five to ten months.[2] It accounts for roughly 1.1% of all cancer cases, and 1.8% of cancer deaths in the United States.[3]
Most signs and symptoms of AML are caused by the crowding out inbone marrow of space for normal blood cells to develop.[10] A lack of normal white blood cell production makes people more susceptible toinfections.[11] A low red blood cell count (anemia) can cause fatigue,paleness,shortness of breath andpalpitations.[11] A lack ofplatelets can lead toeasy bruising, bleeding from the nose (epistaxis), small blood vessels on the skin (petechiae) or gums, orbleeding with minor trauma.[11] Other symptoms may includefever,fatigue worse than what can be attributed to anemia alone,weight loss andloss of appetite.[11]
Enlargement of the spleen may occur in AML, but it is typically mild andasymptomatic.Lymph node swelling is rare in most types of AML, except foracute myelomonocytic leukemia (AMML).[11] The skin can be involved in the form ofleukemia cutis;Sweet's syndrome; or non-specific findings: flat lesions (macules), raised lesionpapules,pyoderma gangrenosum andvasculitis.[11]
Some people with AML may experience swelling of thegums because of infiltration of leukemic cells into the gum tissue.[10] Involvement of other parts of the body such as thegastrointestinal tract,respiratory tract and other parts is possible but less common.[11] One area which has particular importance for treatment is whether there is involvement of themeninges around thecentral nervous system.[11]
Most cases of AML do not have exposure to any identified risk factors.[12][13] However, a number of risk factors for developing AML have been identified. These includeother blood disorders,chemical exposures,ionizing radiation, andgenetic risk factors.[12] Where a defined exposure to past chemotherapy, radiotherapy, toxin or hematologic malignancy is known, this is termedsecondary AML.[14][15]
Other blood disorders, particularlymyelodysplastic syndrome (MDS) and less commonlymyeloproliferative neoplasms (MPN), can evolve into AML;[12] the exact risk depends on the type of MDS/MPN.[16] The presence of asymptomaticclonal hematopoiesis also raises the risk of transformation into AML.[13]
Exposure tochemotherapy, in particularalkylating antineoplastic agents, can increase the risk of subsequently developing AML.[12] Other chemotherapy agents, includingfludarabine,[12] andtopoisomerase II inhibitors are also associated with the development of AML; most commonly after 4–6 years and 1–3 years respectively.[13] These are often associated with specificchromosomal abnormalities in the leukemic cells.[13]
Other chemical exposures associated with the development of AML includebenzene,chloramphenicol andphenylbutazone.[13] The use ofAgent Orange, a militarizedherbicide used in theVietnam War has been associated with the risk of AML due to the herbicide regularly having been contaminated by2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxicdioxin known.[17]
High amounts ofionizing radiation exposure, such as that used forradiotherapy used to treat some forms of cancer, can increase the risk of AML.[12] People treated with ionizing radiation after treatment forprostate cancer,non-Hodgkin lymphoma,lung cancer, andbreast cancer have the highest chance of acquiring AML, but this increased risk returns to the background risk observed in the general population after 12 years.[18] Historically,survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML,[19] as didradiologists exposed to high levels ofX-rays prior to the adoption of modernradiation safety practices.[20]
Traditionally, AML was considered as sporadic, with only few exceptions associated with rare hereditary conditions such asDown syndrome,Fanconi anemia and telomere biology disorders. With the introduction ofNext Generation Sequencing (NGS) in clinical work-up, it is now estimated that up to 5–15% of all AML cases carries a pathogenic variant in a cancer susceptibility genes.[21][22][23]Myeloid neoplasm with germline predisposition is recognized as a distinct category in theWHO 2022 classification of haematolymphoid tumors.[24]
Beingoverweight andobese increase the risk of developing AML, as does any amount of active smoking.[14] For reasons that may relate to substance or radiation exposure, certain occupations have a higher rate of AML; particularly work in the nuclear power industry, electronics or computer manufacturing, fishing and animal slaughtering and processing.[14]
The malignant cell in AML is themyeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor ofmyeloid white blood cells; a normal myeloblast will mature into a white blood cell such as aneosinophil,basophil,neutrophil ormonocyte. In AML, though, a single myeloblast accumulates genetic changes which stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis).[25] Much of the diversity and heterogeneity of AML is because leukemic transformation can occur at a number of different steps along the differentiation pathway.[25] Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems.[26]
Specificcytogenetic abnormalities can be found in many people with AML; the types of chromosomal abnormalities often haveprognostic significance.[26] The chromosomaltranslocations encode abnormalfusion proteins, usuallytranscription factors whose altered properties may cause the "differentiation arrest".[27] For example, in APL, thet(15;17) translocation produces a PML-RARA fusion protein which binds to theretinoic acid receptor element in thepromoters of several myeloid-specific genes and inhibits myeloid differentiation.[28]
Theclinical signs and symptoms of AML result from the growth of leukemic clone cells, which tends to interfere with the development of normal blood cells in the bone marrow.[29] This leads toneutropenia,anemia, andthrombocytopenia.[29] Other symptoms can arise from the infiltration of malignant cells into parts of the body, such as the gingiva and skin.[29]
Many cells develop mutations in genes that affectepigenetics, such asDNA methylation.[2] When these mutations occur, it is likely in the early stages of AML.[2] Such mutations include in the DNA demethylaseTET2 and the metabolic enzymesIDH1 andIDH2,[30] which lead to the generation of a novel oncometabolite,D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such asTET2.[31] Epigenetic mutations may lead to the silencing oftumor suppressor genes and/or the activation ofproto-oncogenes.[32]
Acomplete blood count, which is ablood test, is one of the initial steps in the diagnosis of AML. It may reveal both an excess of white blood cells (leukocytosis) or a decrease (leukopenia), and a low red blood cell count (anemia) and low platelets (thrombocytopenia) can also be commonly seen.[29] Ablood film may show leukemic blast cells.[29] Inclusions within the cells calledAuer rods, when seen, make the diagnosis highly likely.[29] A definitive diagnosis requires abone marrow aspiration and biopsy.[25]
Bone marrow is examined underlight microscopy, as well asflow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g.acute lymphoblastic leukemia), and to provide information about how mature or immature the affected cells are that can assist in classifying the subtype of disease.[25] A sample of marrow or blood is typically also tested for chromosomal abnormalities by routinecytogenetics orfluorescentin situ hybridization. Genetic studies may also be performed to look for specific mutations in genes such asFLT3,nucleophosmin, andKIT, which may influence the outcome of the disease.[33]
Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. The combination of amyeloperoxidase orSudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiatedmonoblastic leukemia from ALL.[34]
The standard classification scheme for AML is theWorld Health Organization (WHO) system.[35][36] According to the WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemicmyeloblasts, except in three forms ofacute myeloid leukemia with recurrent genetic abnormalities: t(8;21), inv(16) or t(16;16), and acute promyelocytic leukemia withPML-RARA, in which the presence of the genetic abnormality is diagnostic irrespective of blast percent.[37]Myeloid sarcoma is also considered a subtype of AML independently of the blast count.[38][39] The olderFrench–American–British (FAB) classification, which is no longer widely used,[36] is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow or peripheral blood for the diagnosis of AML.[40]
Becauseacute promyelocytic leukemia has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescentin situ hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies thechromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence ofPML/RARA fusion protein, which is an oncogenic product of that translocation.[41]
TheWHO classification of AML attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. The French–American–British (FAB) classification system is based on morphology to define specific immunotypes. The World Health Organization (WHO) classification reviews chromosome translocations and evidence of dysplasia.[42] SeeFrench–American–British (FAB) classification system.
Each of the WHO categories contains numerous descriptive subcategories of interest to thehematopathologist andoncologist; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the subtypes listed below.
The revised fourth edition of theWHO Classification of Tumours of Haematopoietic and Lymphoid Tissues[43] was released in 2016. This classification, which is based on a combination of genetic andimmunophenotypic markers and morphology, defined the subtypes of AML and related neoplasms as shown below.[44][45] In 2022, a new classification was published.[24][46]
| Name | Description | ICD-O |
|---|---|---|
| Acute myeloid leukemia with recurrent genetic abnormalities | Includes:[47]
| Multiple |
| AML with myelodysplasia-related changes | This category includes people who have had a prior documentedmyelodysplastic syndrome (MDS) ormyeloproliferative disease (MPD) that then has transformed into AML; who have cytogenetic abnormalities characteristic for this type of AML (with previous history of MDS or MPD that has gone unnoticed in the past, but the cytogenetics is still suggestive of MDS/MPD history); or who have AML with morphologic features of myelodysplasia (dysplastic changes in multiplecell lines).[48] People who have previously received chemotherapy or radiation treatment for a non-MDS/MPD disease, and people who have genetic markers associated with AML with recurrent genetic abnormalities, are excluded from this category. This category of AML occurs most often in elderly people and often has a worse prognosis. Cytogenetic markers for AML with myelodysplasia-related changes include:[49]
| M9895/3 |
| Therapy-related myeloid neoplasms | This category includes people who have had prior chemotherapy and/or radiation and subsequently develop AML or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis.[50] | M9920/3 |
| Myeloid sarcoma | This category includes myeloid sarcoma.[51] | |
| Myeloid proliferations related toDown syndrome | This category includes "transient abnormal myelopoiesis" and "myeloid leukemia associated with Down syndrome". In young children, myeloid leukemia associated with Down syndrome has a much better prognosis than other types of childhood AML. The prognosis in older children is similar to conventional AML.[52] | |
| AML not otherwise categorized | Includes subtypes of AML that do not fall into the above categories:[53] | M9861/3 |
Acute leukemias of ambiguous lineage (also known asmixed phenotype orbiphenotypic acute leukemia) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells, or where both types of cells are present.[55]
TheFrench–American–British (FAB) classification system provides terminology that is still sometimes used, and it remains a valuable diagnostic tool in areas without access togenetic testing, this system has largely become obsolete in favor of the WHO classification, which correlates more strongly with treatment outcomes.[36][56]
The FAB system divides AML into eight subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. AML of types M0 to M2 may be calledacute myeloblastic leukemia. Classification is done by examining the appearance of themalignant cells withlight microscopy and/or by usingcytogenetics to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy.
Six FAB subtypes (M1 through to M6) were initially proposed in 1976,[57] although later revisions added M7 in 1985[58] and M0 in 1987.[59]
| Type | Name | Cytogenetics | Percentage of adults with AML | Immunophenotype[60] | ||||
|---|---|---|---|---|---|---|---|---|
| CD14 | CD15 | CD33 | HLA-DR | Other | ||||
| M0 | acute myeloblastic leukemia, minimally differentiated | 5%[61] | −[62][better source needed] | −[62] | +[62] | +[62] | MPO −[63] | |
| M1 | acute myeloblastic leukemia, without maturation | 15%[61] | − | − | + | + | MPO +[63] | |
| M2 | acute myeloblastic leukemia, with granulocytic maturation | t(8;21)(q22;q22), t(6;9) | 25%[61] | − | + | + | + | |
| M3 | promyelocytic, oracute promyelocytic leukemia (APL) | t(15;17) | 10%[61] | − | + | + | − | |
| M4 | acute myelomonocytic leukemia | inv(16)(p13q22), del(16q) | 20%[61] | <45% | + | + | + | |
| M4eo | myelomonocytic together with bone marroweosinophilia | inv(16), t(16;16) | 5%[61] | +/−[64] | +[65] | +[65] | CD2+[65] | |
| M5 | acute monoblastic leukemia (M5a) oracute monocytic leukemia (M5b) | del (11q), t(9;11), t(11;19) | 10%[61] | >55% | + | + | + | |
| M6 | acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) | 5%[61] | − | +/− | +/− | +/− | Glycophorin + | |
| M7 | acute megakaryoblastic leukemia | t(1;22) | 5%[61] | − | − | + | +/− | CD41/CD61+ |
The morphologic subtypes of AML also include rare types not included in the FAB system, such asacute basophilic leukemia, which was proposed as a ninth subtype, M8, in 1999.[66]
Thefirst-line treatment of acute myeloid leukemia consists primarily ofchemotherapy, and is divided into two phases: induction and consolidation. The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure.[67]Hematopoietic stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses, although transplantation is also sometimes used as front-line therapy for people with high-risk disease. Efforts to use targeted therapies such astyrosine kinase inhibitors in AML continue.[68] Various induction strategies are used, most of which center ondaunorubicin (or a closely related drug) andcytarabine.[69]
Ziftomenib (Komzifti) was approved for medical use in the United States in November 2025.[70]
The goal and purpose of the induction phase is to reach a complete remission. Complete remission does not mean the disease has been cured; rather, it signifies no disease can be detected with available diagnostic methods.[67] All subtypes except acute promyelocytic leukemia are usually giveninduction chemotherapy withcytarabine and ananthracycline such asdaunorubicin oridarubicin.[67] This induction chemotherapy regimen is known as "7+3" (or "3+7"), because the cytarabine is given as a continuous IV infusion for seven consecutive days while theanthracycline is given for three consecutive days as anIV push.[71] Response to this treatment varies with age, with people aged less than 60 years having better remission rates between 60% and 80%, while older people having lower remission rates between 33% and 60%.[67] Because of the toxic effects of therapy and a greater chance of AML resistance to this induction therapy, different treatment, such as that inclinical trials might be offered to people 60–65 years or older.[67]
Acute promyelocytic leukemia is treated withall-trans-retinoic acid (ATRA) and eitherarsenic trioxide (ATO) monotherapy or ananthracycline.[72] A syndrome similar todisseminated intravascular coagulation can develop during the initial few days of treatment or at the time the leukemia is diagnosed, and treatment can be complicated by adifferentiation syndrome characterized by fever, fluid overload and low oxygen levels.[72] Acute promyelocytic leukemia is considered curable.[73] There is insufficient evidence to determine if prescribing ATRA in addition to chemotherapy to adults who have other subtypes of acute myeloid leukemia is helpful.[74]
Even after complete remission is achieved, leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques. If no consolidation therapy or further postremission is given, almost all people with AML will eventually relapse.[67]
The specific type of postremission therapy is individualized based on a person's prognostic factors (see above) and general health.[67] For good-prognosis leukemias (i.e. inv(16), t(8;21), and t(15;17)), people will typically undergo an additional three to five courses of intensive chemotherapy, known as consolidation chemotherapy. This generally involves cytarabine, with the doses administered being higher in younger patients, who are less likely to develop toxicity related to this treatment.[67]
Stem cell transplantation from a donor, calledallogenic stem cell transplantation, is usually pursued if the prognosis is not considered favorable, a person can tolerate a transplant and has a suitable donor.[75] The basis of allogenic stem cell transplantation is on agraft versus leukemia effect whereby graft cells stimulate an immune response against leukemia cells.[75] Unfortunately, this is accompanied by immune responses against other host organs, called agraft versus host disease.[75]
Theoretical therapies have been proposed based on the idea of using stem cell transplantation to replace blood stem cells withgenetically modified versions with altered molecular markers, includingCD45, which is present on most blood cells.[76] A treatment would then be applied, such as anantibody-drug conjugate targeting the healthy version of the marker, in order to kill all blood cells with unmodified markers, including the original cells and the cancerous ones.[76] Theoretical therapies have also been proposed to use genetic engineering to attach syntheticchimeric antigen receptors toT-cells.[76] These would bind to markers present in high levels in AML cells, which includeCD123 andCD135.[76] T-cells could also be modified to target normal CD45 markers, but this requires also modifying the CD-45 of T-cells as well so that they do not target themselves.[76] T-cell immunotherapies are being tested in mice and in early-phase clinical trials,[77] but none has been approved as a standard of care for AML.
Support is necessary throughout treatment because of problems associated with AML and also arising from treatment.[78] Blood transfusions, including of red blood cells and platelets, are necessary to maintain health levels, preventing complications ofanemia (from low red blood cells) andbleeding (from low platelets).[78] AML leads to an increased risk of infections, particularlydrug-resistant strains ofbacteria andfungi.[71]Antibiotics andantifungals can be used both to treat and to prevent these infections, particularlyquinolones.[71][79]
Adding aerobic physical exercises to the standard of care may result in little to no difference in the mortality, in the quality of life and in the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue.[80]
Recent research into the role that epigenetic regulators play in hematopoietic malignancies has yielded new insights in the development of targeted epigenetic therapies as a supportive treatment for AML. The FDA has approved certain epigenetic modifying drugs likeivosidenib andenasidenib, which are used in patients that can no longer receive intensive induction chemotherapy; specifically, they are involved in the therapy ofIDH1 and IDH2 mutations. Further research must be done to prove the efficacy of epigenetic treatments, but the development of new epigenetic therapies along with immunotherapies holds potential in the future treatment of AML.[81]
Acute myeloid leukemia is rare in pregnancy, affecting about 1 in 75,000 to 100,000 pregnant women.[82] It is diagnosed and treated similarly to AML in non pregnancy, with a recommendation that it is treated urgently.[82] However, treatment has significant implications for the pregnancy. First trimester pregnancy is considered unlikely to be viable; pregnancy during weeks 24 – 36 requires consideration of the benefits of chemotherapy to the mother against the risks to the fetus; and there is a recommendation to consider delaying chemotherapy in very late pregnancy (> 36 weeks).[82] Some elements of supportive care, such as which antibiotics to prevent or treat infections, also change in pregnancy.[82]
A study undertaken atGreat Ormond Street Hospital in 2025 discovered that by using a form ofimmunotherapy that involves modifyingT cells from affected patients usingbase editing to applychimeric antigen receptors (CAR), it is possible to enter remission from the disease upon returning the modified cells to the patient's bloodstream.[83][84] The "BE-CAR7" treatment was only trialled on two adults and eight children, with two-thirds of patients becomingcancer free. A furtherbone marrow transplant could help prevent the cancer returning.[85]
Multiple factors influence prognosis in AML, including the presence of specific mutations, and a person with AML's age. In the United States between 2011 and 2016, the median survival of a person with AML was 8.5 months, with the 5 year survival being 24%.[14] This declines with age, with the poorer prognosis being associated with an age greater than 65 years, and the poorest prognosis seen in those aged 75–84.[14]
As of 2001, cure rates inclinical trials have ranged from 20 to 45%;[86][87] although clinical trials often include only younger people and those able to tolerate aggressive therapies. The overall cure rate for all people with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for APL can be very high in some clinical trials.[88]
As of 2021[update], "[I]n APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80% ... Ongoing research in acute myeloid leukemia (AML) is progressing rapidly".Arsenic trioxide andATRA are the "most effective anti-APL agents" as shown by studies from China, India and Iran.[89]
Secondary AML has a worseprognosis, as does treatment-related AML arising after chemotherapy for another previous malignancy. Both of these entities are associated with a high rate of unfavorable genetic mutations.[14][15]
Different genetic mutations are associated with a difference in outcomes. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in APL). About half of people with AML have "normal" cytogenetics lacking identifiable translocations or other large-scale anomalies; they fall into an intermediate risk group. A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment.[90][91][92]
A large number of molecular alterations are under study for their prognostic impact in AML. However, onlyFLT3-ITD,NPM1,CEBPA andc-KIT are currently included in validated international risk stratification schema. These are expected to increase rapidly in the near future.[2]FLT3 internal tandem duplications (ITDs) have been shown to confer a poorer prognosis in AML with normal cytogenetics. SeveralFLT3 inhibitors have undergone clinical trials, with mixed results. Two other mutations –NPM1 and biallelicCEBPA are associated with improved outcomes, especially in people with normal cytogenetics and are used in current risk stratification algorithms.[2]
Researchers are investigating the clinical significance ofc-KIT mutations in AML. These are prevalent, and potentially clinically relevant because of the availability oftyrosine kinase inhibitors, such asimatinib andsunitinib that can block the activity ofc-KIT pharmacologically.[2] It is expected that additional markers (e.g.,RUNX1,ASXL1, andTP53) that have consistently been associated with an inferior outcome will soon be included in these recommendations. The prognostic importance of other mutated genes (e.g.,DNMT3A,IDH1,IDH2) is less clear.[2][30]
Elevatedlactate dehydrogenase level were also associated with poorer outcomes.[93] Use of tobacco is associated with a person having a poorer prognosis,[14] and people who are married and live together have a better prognosis.[14] People who are treated at place with a higher volume of AML have a better prognosis than those who are treated at those in the lowest quartile.[14] As with most forms of cancer,performance status (i.e. the general physical condition and activity level of the person) plays a major role in prognosis as well.[94]
For people in remission afterinduction chemotherapy, residual leukemic cells (minimal residual disease) are associated with higher relapse rates and decreased survival.[95] Furthermore, the presence of specific leukemic cells that are capable of initiating a relapse, the leukemia stem cell (a type ofcancer stem cell) is associated with impaired survival and higher incidence of relapse.[96]
AML is a relatively rare cancer. There were 19,950 new cases in the United States in 2016.[97] In 2018, AML accounted for 1.2% of all cancer deaths in the United States.[13]
The incidence of AML increases with age and varies between countries.[14] The median age when AML is diagnosed ranges between 63 and 71 years in the UK, Canada, Australia and Sweden, compared with 40 to 45 years in India, Brazil and Algeria.[14]
According to 2002 statistics, AML accounts for about 90% of allacute leukemias in adults and is rare in children.[98] Acute leukemias consist of serious medical conditions relating to an original diagnosis ofleukemia, where the abnormal blood cells are immature blood cells (blasts). They are mostly classified in terms ofmyeloid cells orlymphoid cells.[99]
Based on data from United States Cancer Statistics (USCS) Public Use Database for 2001–2017, the 2021 estimate for new cases of AML andacute lymphoblastic leukemia (ALL) are following:[100]
Based on these estimates, AML is about 78% of the total cases.
The rate of therapy-related AML (AML caused by previous chemotherapy) is expected to rise with an increase in the use of chemotherapy, an aging population and more patients surviving their initial chemotherapy treatment; therapy-related disease accounts for just under 10% of all cases of AML.[101] AML is slightly more common in men, with a male-to-female ratio of 1.3:1[102] to 1.4:1.[14] Incidence is also seen to differ by ethnicity, with caucasians having higher recorded incidences and the lowest recorded incidences being in Pacific Islanders and native Alaskans.[14]
In the UK, AML accounts for 31% of all leukemia cases, and around 3,100 people were diagnosed with the disease each year in 2016–2018.[103]
The first published description of a case of leukemia in medical literature dates to 1827 when French physicianAlfred-Armand-Louis-Marie Velpeau described a 63-year-old florist who developed an illness characterized by fever, weakness,urinary stones, and substantialenlargement of the liver and spleen. Velpeau noted the blood of this person had a consistency "like gruel", and speculated the appearance of the blood was due to white corpuscles.[104] In 1845, a series of people who died with enlarged spleens and changes in the "colors and consistencies of their blood" was reported by the Edinburgh-basedpathologist J.H. Bennett; he used the term "leucocythemia" to describe this pathological condition.[105]
The term "leukemia" was coined byRudolf Virchow, the renowned Germanpathologist, in 1856. As a pioneer in the use of thelight microscope in pathology, Virchow was the first to describe the abnormal excess of white blood cells in people with the clinical syndrome described by Velpeau and Bennett. As Virchow was uncertain of theetiology of the white blood cell excess, he used the purely descriptive term "leukemia" (Greek: "white blood") to refer to the condition.[106]
Further advances in the understanding of AML occurred rapidly with the development of new technology. In 1877,Paul Ehrlich developed a technique ofstaining blood films which allowed him to describe in detail normal and abnormal white blood cells.Wilhelm Ebstein introduced the term "acute leukemia" in 1889 to differentiate rapidly progressive and fatal leukemias from the moreindolentchronic leukemias.[107] The term "myeloid" was coined byFranz Ernst Christian Neumann in 1869, as he was the first to recognize white blood cells were made in the bone marrow (Greek:μυєλός,myelos,lit. '(bone) marrow') as opposed to thespleen. The technique ofbone marrow examination to diagnose leukemia was first described in 1879 by Mosler.[108] Finally, in 1900, themyeloblast, which is the malignant cell in AML, was characterized byOtto Naegeli, who divided the leukemias into myeloid and lymphocytic.[109][110]
In 2008, AML became the first cancer genome to be fullysequenced. DNA extracted from leukemic cells were compared to unaffected skin.[111] The leukemic cells contained acquired mutations in several genes that had not previously been associated with the disease.
In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80% ... Ongoing research in acute myeloid leukemia (AML) is progressing rapidly ... In the late 1980s and early 1990s, ATRA and arsenic trioxide were discovered to have major anti-APL activities through their ability to reverse the maturation block, resulting in a gradual differentiation process. Studies from China, India, and Iran that investigated single-agent therapy with ATRA or arsenic trioxide as a frontline therapy showed high CR rates and 5-year disease-free survival rates exceeding 50% to 60%.61-63 This established arsenic trioxide and ATRA as the most effective anti-APL agents. GO was also found to be highly effective
| International | |
|---|---|
| National | |
| Other | |
