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Acute myeloid leukemia in adults: Overview

Acute myeloid leukemia in adults: Overview
Literature review current through: Jan 2024.
This topic last updated: Jan 28, 2022.

INTRODUCTION — Acute myeloid leukemia (AML) comprises a heterogeneous group of aggressive blood cell cancers that arise from clonal expansion of malignant hematopoietic precursor cells in the bone marrow. The leukemic cells interfere with production of normal blood cells, causing weakness, infection, bleeding, and other symptoms and complications.

This topic provides an overview of AML in adults.

Details about specific aspects of AML in adults are presented separately:

(See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia".)

(See "Acute myeloid leukemia: Classification".)

(See "Acute myeloid leukemia: Pathogenesis" and "Acute myeloid leukemia: Molecular genetics" and "Acute myeloid leukemia: Cytogenetic abnormalities".)

(See "Acute myeloid leukemia: Risk factors and prognosis".)

(See "Acute myeloid leukemia: Induction therapy in medically fit adults".)

(See "Acute myeloid leukemia: Overview of complications" and "Involvement of the central nervous system (CNS) with acute myeloid leukemia (AML)".)

(See "Acute myeloid leukemia in younger adults: Post-remission therapy".)

(See "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults" and "Acute myeloid leukemia: Management of medically unfit adults".)

(See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults" and "Initial treatment of acute promyelocytic leukemia in adults".)

EPIDEMIOLOGY — AML is the second most common category of leukemia in adults and the most common type of acute leukemia. Nevertheless, AML is relatively rare and it accounts for approximately 1 percent of adult cancers in the United States, but nearly 2 percent of cancer-related deaths [1]. The median age at diagnosis is approximately 68 years, and the incidence increases with age. There is a modest predominance in men and a higher incidence in non-Hispanic White Americans than other racial and ethnic groups. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Epidemiology'.)

AML has been associated with environmental factors (eg, exposure to chemicals, radiation, tobacco, chemotherapy, retroviruses). In some patients, evolution to AML is preceded by evidence of clonal hematopoiesis manifest as a myelodysplastic syndrome, myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, aplastic anemia, clonal hematopoiesis of indeterminate prognosis (CHIP), or clonal cytopenia of unknown significance (CCUS). The cause of the underlying somatic mutations is unknown for most cases of AML in adults. (See "Acute myeloid leukemia: Pathogenesis" and "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Epidemiology'.)

In rare cases, AML in adults is associated with inherited genetic abnormalities, including mutations or loss of tumor suppressor and/or DNA damage repair genes (eg, trisomy 21; Fanconi anemia; Li-Fraumeni syndrome; Bloom's syndrome; familial mutations of CEBPA, DDX41, RUNX1). Familial disorders may be associated with a personal or family history of other hematologic disorders (eg, cytopenias, particularly thrombocytopenia; immune deficiencies), certain cancers and somatic syndromes, or other known genetic variants (table 1 and figure 1). (See "Familial disorders of acute leukemia and myelodysplastic syndromes".)

PATHOGENESIS — AML is a consequence of malignant transformation of myeloid precursor cells. This transformation results in one or more clones of abnormal cells that can proliferate but are blocked in their ability to differentiate into mature blood cells and to undergo programmed cell death (apoptosis). AML is maintained by a pool of self-renewing leukemic stem cells or committed progenitor cells that are more immature than the bulk population of leukemic cells. (See "Acute myeloid leukemia: Pathogenesis", section on 'Leukemic stem cells'.)

Specific chromosomal abnormalities can be identified in more than half of cases of AML, including recurrent translocations, rearrangements, and gain or loss of entire chromosomes or portions of chromosomes. Some of these chromosomal translocations generate chimeric (ie, fusion) oncogenes. (See "Acute myeloid leukemia: Molecular genetics", section on 'Chromosomal translocations'.)

Point mutations, gene duplications, and gene deletions that are not detectable with routine karyotyping are seen in the great majority of cases. These also affect genes that regulate growth and/or differentiation. Examples include alterations of genes that encode transcription factors, epigenetic regulators, tumor suppressors, DNA repair, signaling molecules, regulators of apoptosis, and other mechanisms. (See "Acute myeloid leukemia: Molecular genetics", section on 'Gene mutations'.)

PRESENTATION

Clinical manifestations — Most patients with AML have clinical manifestations, but some are asymptomatic and present with only laboratory abnormalities. Clinical findings include the following (see "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Clinical presentation'):

Signs and symptoms related to anemia (eg, shortness of breath, weakness, dyspnea), thrombocytopenia (excess bleeding or bruising), and neutropenia (fever, infections) are common. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Clinical presentation'.)

Headache or focal neurologic complaints (eg, due to central nervous system hemorrhage or leukemic meningitis). (See "Involvement of the central nervous system (CNS) with acute myeloid leukemia (AML)".)

Physical findings may include pallor, bleeding, or bruising. Occasional patients manifest hepatomegaly, splenomegaly, or a soft tissue mass due to myeloid sarcoma, but lymphadenopathy is rare. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Clinical presentation' and "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Myeloid sarcoma'.)

Complete blood count with differential typically reveals decreased mature red cells, neutrophils, and/or platelets and may reveal leukocytosis (due to circulating blasts). Serum chemistries may suggest tumor lysis syndrome or other metabolic complications. (See "Hyperleukocytosis and leukostasis in hematologic malignancies" and "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors".)

Leukemic blasts in peripheral blood, bone marrow, and/or other tissues (eg, skin, other organs) may manifest Auer rods (picture 1) or other leukemic features. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Pathologic features'.)

Acute promyelocytic leukemia (APL) is a distinctive syndrome that should be suspected in patients who present with bleeding or bruising, thrombocytopenia, leukemic blasts with coarse or dense cytoplasmic granules, low white blood cell (WBC) count, hypofibrinogenemia and/or few circulating leukemic cells. APL is a medical emergency that requires distinctive and urgent management. Diagnosis and management of APL are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults" and "Initial treatment of acute promyelocytic leukemia in adults".)

Complications/emergencies — AML may be associated with various life-threatening complications and emergencies. Pancytopenia is nearly universal as a result of the underlying disease or its treatment (eg, anemia, infection, bleeding), while others are less common. (See "Acute myeloid leukemia: Overview of complications" and "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Adjunctive care'.)

Particular complications are associated with certain categories of AML (eg, disseminated intravascular coagulation that is most often associated with APL). Further details regarding this type of AML are presented separately. (See "Initial treatment of acute promyelocytic leukemia in adults" and "Molecular biology of acute promyelocytic leukemia" and "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults".)

Other complications are less predictable but may be related to the AML phenotype, comorbid illnesses, or complications of therapy. Further details regarding the diagnosis and management of complications and/or oncologic emergencies associated with AML include the following and are described separately. (See "Acute myeloid leukemia: Overview of complications".)

The following are examples of such emergencies and typical clinical presentations:

Hyperleukocytosis/leukostasis (eg, respiratory and/or neurologic distress in a patient with AML and myeloblasts >50,000/microL, or any patient with AML and myeloblasts >100,000/microL). (See "Acute myeloid leukemia: Overview of complications", section on 'Hyperleukocytosis and leukostasis'.)

Metabolic abnormalities, including tumor lysis syndrome (eg, hyperkalemia, hyperphosphatemia, hyperuricemia, and/or renal insufficiency). (See "Acute myeloid leukemia: Overview of complications", section on 'Tumor lysis syndrome'.)

Bleeding caused by severe thrombocytopenia or coagulation disorders, including disseminated intravascular coagulation that can be caused by sepsis, drugs, AML, or APL. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults".)

Involvement of the central nervous system or eyes (eg, patients with AML and unexplained neurologic or visual symptoms). (See "Involvement of the central nervous system (CNS) with acute myeloid leukemia (AML)", section on 'Clinical presentation' and "Involvement of the central nervous system (CNS) with acute myeloid leukemia (AML)".)

EVALUATION AND DIAGNOSIS — AML should be suspected in any individual with circulating blast cells (immature myeloid cells), unexplained cytopenias (with or without related symptoms, such as bleeding, weakness, infection), or unexplained metabolic/oncologic emergencies (eg, tumor lysis syndrome, hyperleukocytosis). Patients suspected of having AML should be referred urgently for expert evaluation and management.

The diagnosis of AML is based on infiltration of bone marrow or peripheral blood by ≥20 percent blasts that manifest characteristic morphologic, cytochemical, immunophenotypic, and cytogenetic/molecular features. In some cases, even with <20 percent infiltration of bone marrow or peripheral blood, AML can be diagnosed by the presence of myeloid sarcoma or specific chromosomal and/or molecular abnormalities: inv(16), t(16;16), t(8;21) and t(15;17) (or PML-RARA gene rearrangement) (table 2). (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Diagnosis'.)

Details of the evaluation, diagnosis, and differential diagnosis of AML are discussed in greater detail separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia".)

All cases of AML should be classified according to World Health Organization criteria (table 2). (See 'Classification' below.)

Diagnosis of acute promyelocytic leukemia (APL) is described separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults".)

CLASSIFICATION — AML should be categorized according to the World Health Organization (WHO) classification system, based on morphology, immunophenotype, karyotype, molecular features, and clinical features (table 2) [2]. The WHO system has superseded the French-American-British (FAB) classification scheme. (See "Acute myeloid leukemia: Classification".)

Broadly, AML is categorized as one of the following:

AML with recurrent genetic abnormalities, which includes specific AML subtypes with defined structural or molecular abnormalities. (See "Acute myeloid leukemia: Classification", section on 'AML with defining genetic abnormalities'.)

AML with myelodysplasia-related features, without a history of prior cytotoxic therapy; this category includes AML with specific myelodysplasia associated cytogenetic findings (table 3). (See "Acute myeloid leukemia: Classification", section on 'Myelodysplasia-related gene mutations'.)

Therapy-related myeloid neoplasm (also referred to as treatment-related AML). (See "Therapy-related myeloid neoplasms: Epidemiology, causes, evaluation, and diagnosis".)

AML, not otherwise specified (NOS), which does not meet the criteria for the categories described above. (See "Acute myeloid leukemia: Classification", section on 'Other AML subtypes in International Consensus Classification'.)

Myeloid sarcoma. (See "Acute myeloid leukemia: Classification", section on 'Myeloid sarcoma'.)

Further details of the specific chromosomal and molecular genetic abnormalities are presented separately. (See "Acute myeloid leukemia: Classification".)

DIFFERENTIAL DIAGNOSIS — AML in adults must be distinguished from other categories of hematologic malignancy, causes of cytopenias, and syndromes associated with bleeding, infections, and certain metabolic syndromes.

Leukemias — Other hematologic malignancies may resemble AML on the basis of clinical presentation or cellular morphology but can be distinguished based on immunophenotype and karyotypic/molecular abnormalities. The diagnostic features of AML are described above. (See 'Evaluation and diagnosis' above.)

The pathologic features of myelodysplastic syndromes (MDS) may resemble AML, but there is <20 percent infiltration of blasts in bone marrow or blood. Other categories of acute leukemia (eg, acute lymphoblastic leukemia, acute undifferentiated leukemia) are distinguished from AML based on immunophenotype and molecular features. Chronic myeloid leukemia (CML), especially in accelerated phase or blast crisis, may manifest elevated levels of myeloid blasts and is distinguished by the presence of the characteristic t(9;22) chromosomal rearrangement (the "Philadelphia chromosome") and/or BCR-ABL1 oncogene. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Differential diagnosis'.)

Cytopenias — In some cases, the clinical presentation of AML is dominated by cytopenias, with few circulating blasts. Other causes of cytopenias include aplastic anemia, myelofibrosis, MDS, medications, nutritional deficiencies (eg, vitamin B12, folate, copper), bone marrow suppression (eg, alcohol, infection), sequestration from splenomegaly or hepatomegaly, autoimmune disorders (eg, Felty syndrome), hemophagocytic lymphohistiocytosis, and other conditions. (See "Approach to the adult with pancytopenia".)

Other conditions — Tumor lysis syndrome from other causes (eg, lymphoma) or hyperleukocytosis (eg, leukemoid syndromes) should be distinguished by pathologic evaluation, imaging, and other clinical and laboratory features. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors", section on 'Etiology and risk factors' and "Hyperleukocytosis and leukostasis in hematologic malignancies".)

PROGNOSTIC FACTORS — Clinical characteristics and cytogenetic/molecular features are associated with outcomes in AML.

Clinical risk factors — Clinical features that may influence the likelihood of achieving a complete remission and subsequent disease-free survival in AML include age, performance status, medical comorbidities, prior myelodysplastic syndrome or myeloproliferative neoplasm, and history of exposure to cytotoxic agents and/or radiation therapy (table 4) [2,3]. (See "Acute myeloid leukemia: Risk factors and prognosis", section on 'Risk factors'.)

Cytogenetic and molecular features — Outcomes with AML are also associated with certain cytogenetic/molecular features. The European LeukemiaNet (ELN) stratification (table 5) classifies patients as having favorable, intermediate, and adverse risk based on cytogenetic and molecular features. The effects of specific cytogenetic and molecular features on clinical presentation and prognosis are discussed separately. (See "Acute myeloid leukemia: Risk factors and prognosis", section on 'Cytogenetic and molecular features'.)

PRIOR TO TREATMENT

Goals of treatment — The goals of care should be determined by shared decision-making by clinicians and the patient, with input from loved ones. The discussion should acknowledge that AML will be a life-ending disease for most patients yet emphasize the benefits of treatment for short- and long-term outcomes. Goals are influenced by medical fitness, age, personal values and preferences, and prognostic features of the leukemic cells (table 5). Setting of goals of care is discussed in more detail separately. (See "Acute myeloid leukemia: Management of medically unfit adults", section on 'Goals, benefits, and timing of treatment'.)

Achievement of a complete remission (CR; <5 percent blast cells in bone marrow and complete clearance of blasts in blood) (table 6) is an appropriate goal for most patients with AML, since achieving CR is associated with prolongation of survival, improved quality of life, and is necessary for cure of AML. For some patients, treatment with the intent of achieving CR (or even modifying the disease course) may be inadvisable because of advanced age, debility, coexisting medical problems, and/or prior treatment. Response definitions are described in greater detail separately. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Introduction'.)

Pretreatment evaluation — Pretreatment evaluation for AML should include a thorough history and physical examination to identify clinical findings and comorbid conditions that may alter prognosis or complicate management. Particular attention should be paid to the presence of heart disease, renal insufficiency, liver disease, dental conditions, and drug allergies and interactions. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Pretreatment'.)

Assessment should include determination of the level of physical functioning (eg, performance status (table 7), measures of comorbidity) and cognitive function, especially in older adult or frail individuals. (See "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults".)

Laboratory studies should include complete blood count (CBC) with differential, coagulation studies, serum chemistries, and viral serologies. Bone marrow examination should include morphology, flow cytometry, karyotype, and molecular analysis to diagnose and classify AML. A chest X-ray, electrocardiogram, and echocardiogram or MUGA scan to assess ejection fraction should be performed at baseline. Most patients will require a central venous access catheter. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Pretreatment'.)

Human leukocyte antigen (HLA) typing should be considered for patients who are potential candidates for hematopoietic cell transplantation. Typing should also be considered for identifying HLA-matched platelet transfusions in patients who become refractory to platelet transfusions. (See "Acute myeloid leukemia in younger adults: Post-remission therapy", section on 'Unfavorable-risk disease'.)

Older/frail patients — Older patients are more likely to have comorbid illnesses and adverse prognostic features (eg, prior myelodysplastic syndrome). Older patients are often defined as >60 years of age for clinical trials of AML, but fitness for treatment is not strictly determined by chronologic age. Decisions regarding therapy must consider the goals of care, and the potential treatments available to older adult and/or frail individuals [4]. Lower intensity or targeted therapies may be an option for some frail patients. These topics are discussed in greater detail separately. (See "Acute myeloid leukemia: Management of medically unfit adults" and "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults".)

AML with myelodysplasia-related features — AML with a prior history of myelodysplastic syndrome, defined levels of marrow dysplasia, or specific myelodysplasia-associated cytogenetic findings (table 3), but without prior cytotoxic therapy is associated with adverse outcomes. (See "Acute myeloid leukemia: Classification", section on 'Myelodysplasia-related gene mutations'.)

Therapy-related AML — Therapy-related myeloid neoplasms (t-MN) refers to AML in a patient with prior exposure to cytotoxic agents and/or ionizing radiation. T-MN is often associated with associated with high-risk genetic features and adverse prognosis. Diagnosis and management of t-MN are discussed separately. (See "Therapy-related myeloid neoplasms: Epidemiology, causes, evaluation, and diagnosis" and "Acute myeloid leukemia: Classification", section on 'Therapy-related AML'.)

Acute promyelocytic leukemia — Acute promyelocytic leukemia (APL) is a distinct leukemic syndrome that represents a medical emergency that must be identified and treated promptly. Treatment of APL differs significantly from that of other forms of AML. Pathogenesis, clinical presentation, and treatment of APL are discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults" and "Molecular biology of acute promyelocytic leukemia" and "Initial treatment of acute promyelocytic leukemia in adults".)

REMISSION INDUCTION — Selection of therapy for AML should follow assessment of medical fitness and discussion of the goals of therapy, as described above. (See 'Pretreatment evaluation' above and 'Goals of treatment' above.)

Acute promyelocytic leukemia (APL) must be distinguished from other categories of AML. Treatment of APL is described separately. (See "Initial treatment of acute promyelocytic leukemia in adults".)

Intensive remission induction — Selection of induction therapy to achieve complete remission (CR) is based on medical fitness, comorbid illnesses, and goals of therapy. (See 'Pretreatment evaluation' above and 'Goals of treatment' above.)

Treatment of AML in medically fit adults usually begins with intensive remission induction chemotherapy (table 8) [3]. This generally includes a seven-day continuous infusion of cytarabine along with anthracycline treatment on days 1 to 3 (so-called "7+3" regimens). For patients with t-MN and AML with myelodysplasia-related changes, a preparation of liposomal daunorubicin-cytarabine (CPX-351) is an acceptable alternative. Age and medical fitness may also influence the choice of anthracycline and dosing, as discussed separately. (See "Acute myeloid leukemia: Induction therapy in medically fit adults".)

A targeted agent may be added to the induction regimen for patients whose leukemia includes specific mutations. Examples include midostaurin for AML with FLT3 mutation and ivosidenib or enasidenib for treating AML with mutations of IDH1 and IDH2, respectively.

Intensive remission induction therapy can be highly toxic and typically entails hospitalization for several weeks. Toxicities include cytopenias, infections, bleeding/coagulation abnormalities, tumor lysis syndrome, electrolyte imbalances, impaired nutritional status, and other complications. Treatment-related mortality increases with age. (See "Acute myeloid leukemia: Overview of complications".)

Depending upon age, patient selection, and various prognostic features, 60 to 80 percent of younger adults achieve a CR with such regimens, but only about one-third of patients overall are ultimately cured of AML. For patients who do not clear bone marrow blasts following induction therapy, a second, briefer course of remission induction therapy may be given. Most patients who achieve CR do so after one course of induction therapy, but up to one-third occur after two courses of therapy.

Intensive remission induction therapy may not be appropriate or may require modification for older or frail patients or in specific clinical scenarios. (See 'Older/frail patients' above.)

Lower intensity therapy — For patients who are unable to tolerate intensive remission induction therapy, lower intensity therapies may control the disease, prolong survival, and lessen symptoms, but are unlikely to result in long-term disease control.

Lower intensity therapies include targeted agents for patients with specific mutations, hypomethylating agents (eg, azacitidine, decitabine), which are frequently combined with venetoclax or various targeted agents. Discussion of lower intensity therapies for AML are presented separately. (See "Acute myeloid leukemia: Management of medically unfit adults".)

RESPONSE ASSESSMENT — Bone marrow morphology is evaluated to judge the response to therapy. In some settings, more sensitive approaches may be used to assess measurable residual disease (MRD). Definitions of CR and MRD are provided separately. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Introduction'.)

Bone marrow aspirate and biopsy should be performed 7 to 10 days after completion of induction chemotherapy to demonstrate adequate elimination of leukemia cells reflected by marrow hypoplasia and again after recovery of neutrophils and platelets to document the remission status. The first marrow after induction therapy may be inconclusive and lead to a repeat marrow examination 7 to 10 days later. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Remission status'.)

Response to therapy (table 6) can be described as (see "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Introduction'):

Complete remission (CR)

Complete remission (CRi) with incomplete recovery of normal neutrophil or platelet counts

Partial remission (PR)

Resistant disease (sometimes called refractory)

Assessment of MRD can detect persistent leukemic cells with greater sensitivity than conventional morphologic assessment of bone marrow. Techniques that are used to assess MRD include multicolor flow cytometry and various detection methods for specific mutations (eg, next generation sequencing, polymerase chain reaction [PCR] assays). (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Introduction'.)

POSTREMISSION THERAPY — Nearly all patients who initially achieve complete remission (CR) will relapse unless postremission therapy is given. The goal of postremission therapy is to eliminate residual, undetectable disease and achieve long-term disease control and cure. Postremission therapy may include two phases: consolidation and maintenance therapy, which are distinguished by the timing of administration and intensity of treatment.

Consolidation chemotherapy — Consolidation therapy is intensive treatment that follows soon after the attainment of CR. Consolidation generally comprises one or more courses of chemotherapy (usually infusions of high dose cytarabine, so-called HiDAC therapy), autologous hematopoietic cell transplantation (HCT), or allogeneic HCT. (See "Acute myeloid leukemia in younger adults: Post-remission therapy".)

Decisions regarding the optimal consolidation therapy are influenced by the classification of AML (table 2), risk stratification based on chromosomal and molecular genetic features (table 5), and the medical condition of the individual. Additional considerations are whether the patient is a candidate for HCT and if a compatible donor is available for allogeneic HCT. (See "Determining eligibility for allogeneic hematopoietic cell transplantation" and "Determining eligibility for autologous hematopoietic cell transplantation".)

Hematopoietic cell transplantation — HCT is preferred for most patients with intermediate or unfavorable prognosis AML, especially for those <60 years of age. When a suitable donor can be identified, allogeneic HCT is preferable to autologous HCT or consolidation chemotherapy alone for these patients. Increasingly, allogeneic transplants using partially HLA-mismatched donors or umbilical cord blood stem cells has expanded the pool of potential donors. Allogeneic HCT induces an important graft-versus-leukemia effect that is not provided by other approaches but is complicated by short- and long-term toxicities, including acute and chronic graft-versus-host disease (GVHD), which are countered by immunosuppression and other therapies. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Treatment of acute graft-versus-host disease" and "Clinical manifestations and diagnosis of chronic graft-versus-host disease" and "Treatment of chronic graft-versus-host disease" and "Prevention of graft-versus-host disease", section on 'Introduction'.)

Selection of a conditioning regimen and other aspects of allogeneic HCT are discussed separately. (See "Acute myeloid leukemia in younger adults: Post-remission therapy" and "Preparative regimens for hematopoietic cell transplantation" and "Determining eligibility for autologous hematopoietic cell transplantation".)

Maintenance — Maintenance therapy describes nonmyelosuppressive treatment with chemotherapy and/or a targeted therapeutic agent that is administered over a period of months to years. Certain categories of AML may benefit from maintenance therapy with oral azacitidine following recovery from consolidation therapy. (See "Acute myeloid leukemia in younger adults: Post-remission therapy".)

MONITORING — Patients are followed clinically after achieving complete remission (CR), but there is no consensus regarding an optimal schedule and protocol for monitoring disease status.

Determining whether a patient in CR is destined to remain clinically disease-free after postremission therapy is limited by the insensitivity of routine tests on the bone marrow for detecting residual leukemia. Techniques employing real time quantitative polymerase chain reaction (Q-PCR) and/or multiparameter flow cytometry are significantly more sensitive for detecting persistent AML and are being increasingly applied in selected clinical scenarios. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Introduction'.)

RELAPSED/REFRACTORY DISEASE — Relapsed AML refers to leukemia that recurs after achievement of complete remission (CR). Refractory AML is leukemia that did not fully respond with CR to remission induction therapy.

Evaluation includes the pretreatment evaluation described above and should include human leukocyte antigen (HLA) typing for all patients who may be candidates for hematopoietic cell transplantation (HCT). Decisions regarding further therapy are influenced by an estimation of the likelihood of attaining CR, comorbid illnesses (including active infections), eligibility for allogeneic HCT, and the presence of an appropriate HLA-matched donor. Specific approaches that are used to achieve remission for relapsed refractory AML are discussed separately. (See "Treatment of relapsed or refractory acute myeloid leukemia".)

CLINICAL TRIALS — Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health and other sources (eg, clinicaltrials.gov).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute myeloid leukemia".)

SUMMARY

Acute myeloid leukemia (AML) – AML is the most common acute leukemia in adults. AML comprises a heterogeneous group of cancers of blood cells that arise from genetic and epigenetic changes in hematopoietic stem and/or progenitor cells that exhibit abnormal growth and differentiation.

Clinical presentation – Most patients with AML present with findings of cytopenias (eg, fatigue, infections, bleeding), but some exhibit only laboratory abnormalities. (See 'Clinical manifestations' above.)

Others present with a clinical emergency, including hyperleukocytosis/leukostasis, tumor lysis syndrome (TLS), disseminated intravascular coagulation (DIC), or involvement of the central nervous system (CNS) and require urgent management. (See 'Complications/emergencies' above.)

Pathogenesis – AML is associated with characteristic non-random chromosomal abnormalities and genetic abnormalities, many of which are used to classify AML and are associated with response to therapy and prognosis. (See 'Classification' above.)

Evaluation and diagnosis – AML should be suspected in patients with circulating blasts, unexplained cytopenia-related symptoms (eg, bleeding, weakness, infection), and medical complications/emergencies (eg, TLS, DIC). (See 'Evaluation and diagnosis' above.)

Diagnosis typically requires ≥20 percent blasts in marrow or blood, but it can also be established by specific chromosomal and/or molecular abnormalities or presence of a myeloid sarcoma.

Classification – AML should be categorized according to the World Health Organization (WHO) classification system, based on morphology, immunophenotype, karyotype, molecular features, and clinical features (table 2). (See 'Classification' above.)

Goals of care – Goal of care require shared decision-making by clinicians and the patient/family. For many patients, achievement of long-term disease control/cure is an appropriate goal. For some patients who are older, frail, or with severe comorbid conditions, lessening symptoms and/or prolonging life may be more appropriate. (See 'Goals of treatment' above.)

Management – Treatment decisions are informed by comorbid illnesses, age, AML category, and other factors. AML is rapidly lethal if untreated, but intensive treatment can achieve complete remission (CR) in more than two-thirds of younger adults and ultimately cure approximately one-third.

Acute promyelocytic leukemia (APL) requires urgent and distinctive treatment. (See "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults" and "Initial treatment of acute promyelocytic leukemia in adults".)

Initial treatment of most categories of AML includes:

Remission induction therapy includes intensive combination chemotherapy (table 8) that is typically accompanied by profound cytopenias, infections, and other treatment complications and requires extended hospitalization. (See 'Intensive remission induction' above.)

Lower intensity treatments may be suitable for patients who cannot tolerate intensive remission induction therapy; such treatment can lessen symptoms and prolong survival but is unlikely to achieve longer-term disease control. (See 'Lower intensity therapy' above.)

Response assessment – Bone marrow morphology, with or without assessment of measurable residual disease (MRD), is used to judge response to therapy. (See 'Response assessment' above.)

Postremission management – Postremission management in patients who achieve CR is based on prognostic features, age, comorbidities, and patient preference. For some patients this may include further chemotherapy, a targeted agent, or allogeneic hematopoietic cell transplantation (HCT). (See 'Postremission therapy' above.)

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