Acute Myelogenous Leukemia (AML) Guidelines 

Updated: Aug 27, 2015
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
  • Print

Issuing Organizations

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

  • National Comprehensive Cancer Network (NCCN) [1]
  • European Society of Medical Oncology (ESMO) [2]
Next:

Diagnosis

Both the NCCN and ESMO guidelines recommend including the following tests in the diagnostic work-up for AML [1, 2] :

  • Complete blood count (CBC) with manual differential and routine chemistry profile (including liver function tests, serum creatinine, 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 c-KIT, FLT3-ITD, NPM1, and CEBPA
  • HLA typing of patient and family

ESMO guidelines include the following additional tests to the diagnostic workup for all patients [2] :

  • Imaging studies, including dental survey and computed tomography (CT) scan of the chest and abdomen, or chest x-ray and abdominal ultrasound
  • 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.

The NCCN further recommends the following tests if neurologic symptoms are present [1] :

  • CT or magnetic resonance imaging (MRI) scan
  • 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. [1, 2]

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.{Ref 1} See Table 1, below.

Table 1 AML Cytogenetic Risk Factors – National Comprehensive Cancer Network (Open Table in a new window)

Risk Group Cytogenetic Abnormality
Better Risk inv(16), t(16;16), t(8;21), t(15;17)
Intermediate Risk Normal cytogenetics, +8 alone, t(9;11); other chromosomal abnormalities
Poor Risk Complex (≥3 clonal chromosomal abnormalities)



Monosomal karyotype



-5, 5q-, -7, 7q-, 11q23 other than t(9;11), inv(3), t(3;3), t(6;9), t(9;22)



The ESMO risk classifications vary slightly from those of the NCCN. [2] See Table 2, below.

Table 2 AML Cytogenetic Risk Factors – European Society of Medical Oncology (Open Table in a new window)

Risk Group Cytogenetic Abnormality
Favorable inv(16), t(8;21), t(15;17) Biallelic CEBPα



mutation with normal cytogenetics



Normal karyotype with NPM mutation and no FLT3 ITD



Intermediate Risk Normal cytogenetics and no adverse molecular features, FLT3 ITD with normal karyotype
Adverse Risk Complex karyotype abnormalities (≥3 clonal chromosomal abnormalities)



Monosomal karyotype



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. [1, 2]

Previous
Next:

Treatment & Management

Both the NCCN and the ESMO guidelines are in agreement with the following general recommendations for treatment [1, 2] :

  • 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, and combined with anthracycline-based chemotherapy once the diagnosis of APL is confirmed

The NCCN guidelines give more 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.

Previous
Next:

Supportive Care

The NCCN guidelines recommend that all patients receive supportive care that includes the following [1] :

  • Use of leukodepleted, irradiated blood products
  • Tumor lysis prophylaxis * Not all AML are at high risk for TLS.  Multivariate analysis showed that 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 10(9)/L were independent risk factors for Clinical TLS and Laboratory TLS. The scoring system, based on pretreatment WBC counts, and uric acid and LDH serum levels, had excellent discrimination and was accurate for predicting CTLS and LTLS. Ref. Haematologica. 2008 Jan;93(1):67-74. doi: 10.3324/haematol.11575.
  • Growth factors for post-remission therapy may be considered but may impact interpretation of the bone marrow evaluation
  • Use and choice of antibiotics prophylaxis should be based on the prevailing organisms and their drug resistance patterns

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
Previous
Next: