Acute Myeloid Leukemia (AML) Guidelines

Updated: Jul 26, 2023
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Guidelines Summary

Guidelines on the initial diagnostic workup of acute leukemia (AL) have been issued by the College of American Pathologists and the American Society of Hematology (CAP/ASH). [116]

Guidelines for the management of acute myeloid leukemia (AML) have been issued by the following organizations:

  • National Comprehensive Cancer Network (NCCN) [25]
  • European Society for Medical Oncology (ESMO) [117]
  • ASH [118]


CAP/ASH guidelines on the initial diagnostic workup of AL include the following recommendations [116] :

  • A complete diagnosis of AL requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and, often, molecular genetic testing.
  • The treating clinician should provide relevant clinical data, including physical examination and imaging findings, or ensure that those data are readily accessible by the pathologist.
  • The pathologist should review recent or concurrent complete blood cell (CBC) counts and leukocyte differentials and evaluate a peripheral blood (PB) smear.
  • Obtain a fresh bone marrow (BM) aspirate for all patients suspected of AL, a portion of which should be used to make BM aspirate specimens for morphologic evaluation. If performed, the pathologist should evaluate an adequate BM trephine core biopsy, BM trephine touch preparations, and/or marrow clots, in conjunction with the BM aspirates.
  • In addition to morphologic assessment (blood and BM), obtain sufficient samples and perform conventional cytogenetic analysis (ie, karyotype), appropriate molecular-genetic and/or fluorescence in situ hybridization (FISH) testing, and flow cytometry immunophenotyping (FCIp). The flow cytometry panel should be sufficient to distinguish AML (including acute promyelocytic leukemia), T-ALL (including early T-cell precursor leukemias), B-cell precursor ALL (B-ALL), and AL of ambiguous lineage for all patients diagnosed with AL. Molecular genetic and/or FISH testing does not, however, replace conventional cytogenetic analysis.
  • For patients with suspected or confirmed AL, cytochemical studies to assist in the diagnosis and classification of AML may be requested and evaluated.
  • The treating clinician or pathologist may use cryopreserved cells or nucleic acid, nondecalcified formalin fixed paraffin-embedded (FFPE) tissue, or unstained marrow aspirate or PB specimens obtained and prepared from PB, BM aspirate, or other involved tissues for molecular or genetic studies in which the use of such material has been validated.
  • For patients with suspected or confirmed AL, the pathologist may use flow cytometry in the evaluation of CSF.
  • For patients who present with extramedullary disease without BM or blood involvement, a tissue biopsy should be evaluated and processed for morphologic, immunophenotypic, cytogenetic, and molecular genetic studies, as recommended for the BM.
  • For pediatric patients with suspected or confirmed B-ALL, ensure testing for t(12;21)(p13.2;q22.1); ETV6-RUNX1, t(9;22)(q34.1;q11.2); BCR-ABL1, KMT2A (previously MLL) translocation; iAMP21; and trisomy 4 and 10 is performed.
  • For adult patients with suspected or confirmed B-ALL, ensure testing for t(9;22)(q34.1;q11.2) and BCR-ABL1. In addition, testing for KMT2A (previously MLL) translocations may be performed.
  • For pediatric and adult patients with suspected or confirmed AML of any type, ensure testing for FLT3-ITD. The pathologist or treating clinician may order mutational analysis that includes, but is not limited to, IDH1, IDH2, TET2, WT1, DNMT3A, and/or TP53 for prognostic and/or therapeutic purposes.
  • For patients with suspected acute promyelocytic leukemia (APL), ensure rapid detection of PML-RARA. The treating physician should also order appropriate coagulation studies to evaluate for disseminated intravascular coagulation (DIC).

Both the NCCN and ESMO guidelines recommend including the following tests in the diagnostic workup for AML [25, 117] :

  • Complete blood count (CBC) with manual differential, comprehensive metabolic panel, lactate dehydrogenase [LDH], and uric acid
  • Coagulation profile – Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen
  • Bone marrow aspiration and biopsy, including classical cytogenetics, immunophenotyping, and molecular testing for ASXL1 , c-KIT, FLT3-ITD, FLT3-TKD, NPM1, CEBPA, IDH1, IDH2, RUNX1 , TP53, and other mutations 
  • HLA typing of patient and family

NCCN guidelines also include vitamin B12 and folic acid evaluation. [25]

ESMO guidelines include the following additional tests to the diagnostic workup for all patients [117] :

  • Genetic counselling in select patients with a family history positive for cancer or an inherited condition potentially associated with leukemia
  • Sperm preservation in men (if desired by patient)
  • Pregnancy test in women

Although not specifically mentioned in the NCCN guidelines, sperm preservation and pregnancy testing are standard practice in the United States.

ESMO and NCCN guidelines further recommend the following tests if neurologic symptoms are present [25, 117] :

  • CT of brain without contrast, if CNS hemorrhage suspected
  • Brain magnetic resonance imaging (MRI) with contrast, if leukemic meningitis suspected
  • Positron emission tomography (PET)/CT, if clinical suspicion for extramedullary disease
  • Lumbar puncture

Many commonly used induction regimens contain an anthracycline or anthracenedione. Therefore, assessment of cardiac risk factors and assessment of myocardial function (by echocardiogram or multigated acquisition [MUGA] scan) are a standard part of the diagnostic workup. [25, 117]

The risk pattern in AML is determined not only by cytogenetic abnormalities (eg, chromosomal translocations, deletions, or duplications) but also by molecular mutations that lead to over- or under-expressions of proteins. [25, 117] See Table 3, below.

Table 3 AML Cytogenetic Risk Factors (Open Table in a new window)

Risk Group

Cytogenetic Abnormality


t(8;21)(q22;q22.2); RUNX1-RUNX1T1

inv(16)(p13.1q22) or t(16;16)(p13.1q22); CBFB-MYH11 

Biallelic mutated CEBPA

Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow 

Intermediate Risk

Mutated NPM1 and FLT3-ITDhigh

Wild-type NPM1 without FLT3-ITD or with FLT3- ITDlow  (without adverse risk genetic lesions)

t(9;11)(p21.3;q23.3); MLLT3-KMT2A

Cytogenetic abnormalities not classified as favorable or adverse

Poor Risk

t(6;9)(p23;q34.1); DEK-NUP214

t(v;11q23.3); KMT2A rearranged

t(9;22)(q34.1;q11.2); BCR-ABL1

inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM (EVI1)

-5 or del(5q); -7; -17/abn(17p)

Complex karyotype, monosomal karyotype

Wild type NPM1 and FLT3- ITDhigh

Mutated RUNX1

Mutated ASXL1

Mutated TP53

According to both guidelines, the finding of a translocation between chromosomes 15 and 17, or t(15;17), is associated with a diagnosis of acute promyelocytic leukemia (APL), an AML subtype that is treated and monitored differently than other subtypes. [25, 117]


Both the NCCN and the ESMO guidelines are in agreement with the following general recommendations for treatment [25, 117] :

  • Treatment should be given only in specialized medical centers that follow a multidisciplinary approach and that offer the possibility of enrollment in clinical trials

  • Possible curative treatments include induction chemotherapy (incorporating an anthracycline and cytarabine); post-remission (consolidation) therapy; and, in intermediate to high-risk patients, possible allogeneic stem cell transplantation

  • All-trans retinoic acid (ATRA) should be started immediately if APL is suspected

The NCCN guidelines give detailed recommendations based on patient characteristics such as age, presence of comorbid conditions affecting performance status, and preexisting myelodysplasia. Among the recommendations is that patients with poor performance status, significant comorbities, and/or advanced age (ie, some patients ≥ 60 years old and most patients ≥ 70 years old) should receive low-intensity therapy or supportive care if a clinical trial is not available. [25]

Older adults

ASH guidelines for treatment of newly diagnosed AML in older adults include the following recommendations and suggestions [118] :

  • ASH recommends offering antileukemia therapy over best supportive care, and suggests intensive antileukemic therapy over less-intensive antileukemic therapy, for patients who are candidates for such therapy. 
  • For patients who achieve remission after ≥1 cycle of intensive antileukemic therapy and who are not candidates for allogeneic transplantation, ASH suggests postremission therapy over no additional therapy. 
  • For patients considered appropriate for antileukemia therapy but not intensive antileukemic therapy, ASH suggests using monotherapy with either a hypomethylating agent or low-dose-cytarabine, rather than combining either of those drugs with other agents; however, ASH notes that this guidance may change with upcoming reporting of randomized trials showing a benefit of combination therapies over monotherapy.
  • For patients who achieve a response after receiving less-intensive therapy, ASH suggests continuing therapy indefinitely until progression or unacceptable toxicity over stopping therapy.
  • For patients who are no longer receiving antileukemic therapy, ASH suggests having red blood cell transfusions available over not having transfusions available.

Supportive Care

The NCCN guidelines recommend that all patients receive supportive care that includes the following [25] :

  • Use of leukodepleted, irradiated blood products

  • Tumor lysis prophylaxis — Not all AML patients are at high risk for tumor lysis syndrome (TLS). Independent risk factors for TLS are pretreatment serum lactate dehydrogenase (LDH) levels above laboratory normal values, creatinine > 1.4 mg/dL, uric acid > 7.5 mg/dL and white blood cell (WBC) counts > 25 x 109/L.

  • Growth factors for post-remission therapy may be considered but may impact interpretation of the bone marrow evaluation

  • Use and choice of antibiotics for prophylaxis should be based on the prevailing organisms and their drug resistance patterns

  • Patients receiving high-dose cytarabine require neurologic assessment before each dose. Cytarabine should be stopped in those who develop cerebellar toxicity.  

For individuals receiving treatment for APL, the supportive care recommendations also include the following:

  • Aggressive transfusion support with platelets, fresh frozen plasma (FFP), and cryoprecipitate to manage clinical coagulopathy and overt bleeding

  • Close monitoring for possible APL differentiation syndrome, with initiation of dexamethasone at the first sign of symptoms such as acute weight gain (monitor daily weights) and shortness of breath.

  • Prophylaxis with prednisone for individuals receiving ATRA plus arsenic trioxide

  • In patients receiving arsenic trioxide, monitoring with serial electrocardiograms (to evaluate the corrected QT interval) and meticulous replacement of potassium and magnesium, to maintain high-normal levels of these electrolytes

The NCCN recommends that the following not be used in APL patients:

  • Leukapheresis, except in life-threatening cases with leukostasis that is unresponsive to other treatment

  • Myeloid growth factors