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Acute Myeloid Leukemia (AML)

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General Information

Description

  • heterogeneous hematopoietic stem cell disorders characterized by incomplete maturation of blood cells and reduced production of normal hematopoietic elements1

Also called

  • acute myelogenous leukemia
  • acute nonlymphocytic leukemia (ANLL)
  • acute non-lymphocytic leukemia
  • acute myeloblastic leukemia
  • acute granulocytic leukemia
  • acute myelocytic leukemia
  • acute monocytic leukemia

Types

  • World Health Organization (WHO) 2016 classification of AML
    • AML with recurrent genetic abnormalities
      • AML with t(8;21)(q22;q22), (RUNX1-RUNX1T1)
      • AML with inv(16)(p13q22) or t(16;16)(p13;q22), (CBFB/MYH11)
      • acute promyelocytic leukemia (APL) with PML-RARA (formerly APL with t[15;17][q22;q12];PML/RARA)
      • AML with t(9;11)(p22;q23); MLLT3-KMT2A (formerly MLL)
      • AML with t(6;9)(p23;q34), (DEK-NUP214)
      • AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2), GATA2, MECOM (formerly RPN1-EVI1)
      • AML (megakaryoblastic) with t(1;22)(p13;q13), (RBM15-MKL1)
      • AML with mutated NPM1 (new in 2016)
      • AML with biallelic mutations of CEBPA (new in 2016)
      • AML with BCR-ABL1 (provisional, new in 2016)
      • AML with mutated RUNX1 (provisional, new in 2016)
    • AML with myelodysplasia (MDS)-related changes
      • prior history of myelodysplastic syndrome (MDS)
      • MDS-related cytogenetic abnormality
      • multilineage dysplasia
    • therapy-related myeloid neoplasms
    • AML, not otherwise specified
      • AML, minimally differentiated
      • AML without maturation
      • AML with maturation
      • acute myelomonocytic leukemia
      • acute monoblastic/acute monocytic leukemia
      • pure erythroid leukemia
      • acute megakaryoblastic leukemia
      • acute basophilic leukemia
      • acute panmyelosis with myelofibrosis
    • myeloid sarcoma
    • myeloid proliferations related to Down syndrome
      • transient abnormal myelopoiesis
      • acute myeloid leukemia associated with Down syndrome
  • Reference - 27069254Blood 2016 May 19;127(20):2391OpenInNewfull textOpenInNew

Response assessment

  • National Comprehensive Cancer Network (NCCN) and European LeukemiaNet definitions for treatment response in acute myeloid leukemia (AML)
    • morphologic leukemia-free state
      • bone marrow < 5% blasts in an aspirate with spicules
      • no blasts with Auer rods or persistence of extramedullary disease
    • complete remission (CR)
      • morphologic complete remission
        • bone marrow < 5% blasts in bone marrow aspirate
        • absolute neutrophil count (ANC) > 1,000/mcL
        • platelets ≥ 100,000/mcL
        • no residual evidence of extramedullary disease
        • independence from red blood cell transfusions
      • cytogenetic complete response - cytogenetics normal (in those with previously abnormal cytogenetics)
      • molecular complete response - molecular studies negative (only clinically relevant in patients with acute promyelocytic leukemia or who are positive for Philadelphia chromosome [Ph+])
      • CR with incomplete blood count recovery (CRi) defined as meeting all criteria for CR except ANC < 1,000/mcL or platelets < 100,000/mcL
    • partial remission
      • used in clinical trials, not a goal for standard therapy
      • defined as normalization of blood counts as defined in CR, with both
        • decrease of ≥ 50% in percentage of blasts
        • bone marrow blast percentage 5%-25%
    • relapse following complete response defined as any of
      • reappearance of leukemic blasts in peripheral blood
      • > 5% blasts in bone marrow, not due to another cause (for instance, bone marrow regeneration after consolidation therapy)
      • extramedullary relapse
    • molecular monitoring for relapse has shown good correlation with other definitions of relapse in several studies, but is currently limited by a lack of standardization
    • References
  • European Society for Medical Oncology (ESMO) defines treatment response as all of the following
    • blast clearance in bone marrow to < 5% of all nucleated cells
    • morphologically normal hematopoiesis
    • return of peripheral blood counts to normal
    • clearance of infections contracted during therapy-induced aplasia
    • Reference - ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of adult AML (23970018Ann Oncol 2013 Oct;24 Suppl 6:vi138OpenInNew)

Performance status scales

  • performance status evaluation to aid treatment decisions
    Table 1. ECOG or WHO Performance Status Scale
    Grade Criteria
    0Fully active, able to carry on all predisease performance without restriction
    1Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (such as light house work or office work)
    2Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about > 50% of waking hours
    3Capable of only limited self-care, confined to bed or chair > 50% of waking hours
    4Completely disabled; cannot carry on any self-care; totally confined to bed or chair
    5Dead

    Abbreviations: ECOG, Eastern Cooperative Oncology Group; WHO, World Health Organization.

    Reference - 7165009Am J Clin Oncol 1982 Dec;5(6):649OpenInNew.

    Table 2. Karnofsky Performance Status Scale
    Definitions Rating Criteria
    Able to carry on normal activity; no special care needed100%Normal, no complaints, no evidence of disease
    90%Able to carry on normal activity; minor signs or symptoms of disease
    80%Normal activity with effort; some signs or symptoms of disease
    Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed70%Cares for self; unable to carry on normal activity or to do active work
    60%Requires occasional assistance, but is able to care for most personal needs
    50%Requires considerable assistance and frequent medical care
    Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly40%Disabled; requires special care and assistance
    30%Severely disabled; hospital admission is indicated although death not imminent
    20%Very sick; hospital admission necessary; active supportive treatment necessary
    10%Moribund; fatal processes progressing rapidly
    0%Dead
    Reference - 2071835J Gerontol 1991 Jul;46(4):M139OpenInNew, 8156514Cancer 1994 Apr 15;73(8):2087OpenInNew.

References

General references used

  1. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013 Feb 9;381(9865):484-95OpenInNew
  2. O'Donnell MR, Tallman MS, Abboud CN, et al. Acute Myeloid Leukemia. Version 1.2015. In: National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines). NCCN 2014 Dec from NCCN websiteOpenInNew (free registration required)
  3. Heerema-McKenney A, Arber DA. Acute myeloid leukemia. Hematol Oncol Clin North Am. 2009 Aug;23(4):633-54OpenInNew
  4. Jabbour EJ, Estey E, Kantarjian HM. Adult acute myeloid leukemia. Mayo Clin Proc. 2006 Feb;81(2):247-60OpenInNew, correction can be found in Mayo Clin Proc 2006 Apr;81(4):566
  5. British Committee for Standards in Haematology; Milligan DW, Grimwade D, Cullis JO, et al. Guidelines on the management of acute myeloid leukaemia in adults. Br J Haematol. 2006 Nov;135(4):450-74OpenInNew

Recommendation grading systems used

  • British Committee for Standards in Haematology (BCSH) grading system for recommendations
    • grades of recommendations
      • Grade A - ≥ 1 randomized controlled trial in body of literature of overall good quality and consistency addressing specific recommendation (evidence levels Ia and Ib)
      • Grade B - well-conducted clinical studies but no randomized clinical trials on topic of recommendation (evidence levels IIa, IIb, and III)
      • Grade C - expert committee reports or opinions and/or clinical experiences of respected authorities; absence of directly applicable clinical studies of good quality (evidence level IV)
    • levels of evidence
      • Level Ia - evidence from meta-analysis of randomized controlled trials
      • Level Ib - evidence from ≥ 1 randomized controlled trial
      • Level IIa - evidence from ≥ 1 well-designed controlled study without randomization
      • Level IIb - evidence from ≥ 1 other type of well-designed quasi-experimental study
      • Level III - evidence from well-designed nonexperimental descriptive studies, such as comparative studies, correlation studies, and case studies
      • Level IV - evidence from expert committee reports or opinions and/or clinical experiences of respected authorities
  • European Society for Medical Oncology (ESMO) grades of recommendation
    • grades of recommendation
      • Grade A - evidence of level I or consistent findings from multiple studies of types II, III, or IV
      • Grade B - evidence of level II, III, or IV and findings are generally consistent
      • Grade C - evidence of level II, III, or IV but findings are inconsistent
      • Grade D - little or no systematic empirical evidence
    • levels of evidence
      • Level I - evidence obtained from meta-analysis of multiple, well-designed, controlled studies; randomized trials with low false-positive and low false-negative errors (high power)
      • Level II - evidence obtained from at least 1 well-designed experimental study; randomized trials with high false-positive and/or negative errors (low power)
      • Level III - evidence obtained from well-designed, quasi-experimental studies such as nonrandomized, controlled single-group, pre-post, cohort, and time or matched case-control series
      • Level IV - evidence from well-designed, nonexperimental studies such as comparative and correlational descriptive and case studies
      • Level V - evidence from case reports
  • National Comprehensive Cancer Network (NCCN) categories of evidence and consensus
    • Category 1 - based on high-level evidence, there is uniform NCCN consensus that the intervention is appropriate
    • Category 2A - based on lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate
    • Category 2B - based on lower-level evidence, there is NCCN consensus that the intervention is appropriate
    • Category 3 - based on any level of evidence, there is major NCCN disagreement that the intervention is appropriate

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special Acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T114798, Acute Myeloid Leukemia (AML); [updated 2018 Dec 04, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T114798. Registration and login required.
  • KeyboardArrowRight

    Overview and Recommendations

    • Background

    • Evaluation

    • KeyboardArrowRight

      Management

      • Initial Management

      • Management of relapse

  • Related Summaries

  • KeyboardArrowRight

    General Information

    • Description

    • Also called

    • Types

    • Response assessment

    • Performance status scales

  • KeyboardArrowRight

    Epidemiology

    • Who is most affected

    • Incidence/Prevalence

    • Likely risk factors

    • Possible risk factors

    • Factors not associated with increased risk

    • Associated conditions

  • Etiology and Pathogenesis

  • KeyboardArrowRight

    History and Physical

    • History

    • KeyboardArrowRight

      Physical

      • General physical

      • Skin

      • HEENT

      • Neuro

  • KeyboardArrowRight

    Diagnosis

    • Making the diagnosis

    • Differential diagnosis

    • Testing overview

    • Blood tests

    • Biopsy and pathology

  • KeyboardArrowRight

    Management

    • Initial management of AML and maintenance therapy

    • Management of relapse of AML

    • Surveillance

  • KeyboardArrowRight

    Complications and Prognosis

    • Complications

    • KeyboardArrowRight

      Prognosis

      • General concepts

      • Risk stratification

      • Prognostic prediction rules

      • Prognosis by AML type

      • Prognosis in elderly patients

      • Prognosis by performance status

      • KeyboardArrowRight

        Prognosis by gene evaluation

        • General information

        • FLT3 mutations

        • Nucleophosmin (NPM1) gene mutation

        • CEBPA mutation

        • KIT mutation

        • Wilms' tumor gene 1 (WT1) mutation

        • Multigene expression profiling and signatures

        • Other genetic associations

      • Other prognostic considerations

  • Prevention and Screening

  • KeyboardArrowRight

    Quality Improvement

    • Physician Quality Reporting System Quality Measures

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • World Health Organization (WHO) guidelines

      • International guidelines

      • United States guidelines

      • United Kingdom guidelines

      • Canadian guidelines

      • European guidelines

      • Asian guidelines

      • Central and South American guidelines

      • Australian and New Zealand guidelines

    • Review articles

    • MEDLINE search

  • Patient Information

  • KeyboardArrowRight

    ICD Codes

    • ICD-10 codes

  • KeyboardArrowRight

    References

    • General references used

    • Recommendation grading systems used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special Acknowledgements

    • How to cite

Recommendations Editor
Esther Jolanda van Zuuren MD
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Affiliations

Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands

Conflicts of Interest

Dr. van Zuuren declares no relevant financial conflicts of interest.

Deputy Editor
William Aird MD
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Affiliations

Deputy Editor of Hematology, Nephrology and Oncology, Dynamed; Massachusetts, United States; Professor of Medicine, Harvard Medical School; Massachusetts, United States

Conflicts of Interest

Dr. Aird declares no relevant financial conflicts of interest.

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Acute myelocytic leukemia

Acute myelocytic leukemia

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