Acute Myeloid Leukemia (AML) Prognosis

Findings from cytogenetic and molecular analysis of the bone marrow are important prognostic factors.1 The risk pattern in AML is determined not only by cytogenetic abnormalities, but also by certain molecular mutations leading to over- or under-expressions of one of many proteins.2,3

Risk Status Based on Validated Cytogenetics and Molecular Abnormalitiesa,b

Risk Category* Genetic Abnormality
Favorable
  • t(8;21)(q22;q22.1); RUNX1M-RUNX1T1
  • inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
  • Mutated NPM1 without FLT3-ITD or with FLT3-ITD low†
  • Biallelic mutated CEBPA
Intermediate
  • Mutated NPM1 and FLT3-ITD high†
  • Wild-type NPM1 without FLT3-ITD or with FLT3-ITD low†
    (without adverse-risk genetic lesions)
  • t(9;11)(p21.3;q23.3); MLLT3-KMT2A
  • Cytogenetic abnormalities not classified as favorable or adverse
Poor/adverse
  • 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-ITD high†
  • Mutated RUNX1
  • Mutated ASXL1
  • Mutated TP53#

aDohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
bFrequencies, response rates, and outcome measures should be reported by risk category, and, if sufficient numbers are available, by specific genetic lesions indicated.
*Prognostic impact of a marker is treatment-dependent and may change with new therapies.
Low, low allelic ratio (<0.5); high, high allelic ratio (≥0.5); semiquantitative assessment of FLT3-ITD allelic ratio (using DNA fragment analysis) is determined as ratio of the area under the curve “FLT3-ITD” divided by area under the curve “FLT3-wild type”; regardless of FLT3 allelic fractions, patients should be considered for bone marrow transplant, though recent studies indicate that AML with NPM1 mutation and FLT3-ITD low allelic ratio may also have a more favorable prognosis and patients should not routinely be assigned to allogeneic hematopoietic-cell transplantation (allo-HCT). FLT3 allelic ratio is not yet pervasively used, and if not available, the presence of an FLT3 mutation should be considered high-risk unless it occurs concurrently with an NPM1 mutation, in which case it is intermediate risk. As data emerge, this measure will evolve.
The presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concurrent adverse-risk gene mutations.
§Three or more unrelated chromosome abnormalities in the absence of 1 of the World Health Organization (WHO)-designated recurring translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1.
||Defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor [CBF] AML).
These markers should not be used as an adverse prognostic marker if they co-occur with favorable-risk AML subtypes.
#TP53 mutations are significantly associated with AML with complex and monosomal karyotype.

Survival Rates Vary by Age

5-year AML Survival Rates4

Age Cohort Survival Rate
<60 Up to 50%
≥60 3% to 8%

 

Although there have been advances in the treatment of AML, prognosis in the elderly remains poor and they account for the majority of new diagnoses. Even with current treatments, up to 70% of patients 65 years or older die of their disease within 1 year of diagnosis.5 AML is particularly devastating in the older patient population considering most people living in the Western world can expect to live well into their eighth decade.6

There are many reasons for poorer outcomes in older adults6:

  • Older patients are often frail and have comorbidities that make them unable to tolerate, or ineligible for, treatment modalities
  • From a clinical standpoint, elderly patients are more likely to have received previous treatment, radiation, or have had a hematologic disease
  • Unlike younger patients, elderly patients are more likely to have multiple chromosomal abnormalities

References: 1. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350(16):1617-1628. 2. Nardi V, Hasserjian RP. Genetic testing in acute myeloid leukemia and myelodysplastic syndromes. Surg Pathol Clin. 2016;9(1):143-163. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 29, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916-1924. 5. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441. 6. Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7.