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Validation of the ELN 2017 risk stratification for acute myeloid leukemia

May 27, 2022
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Learning objective: After reading this article, learners will be able to cite a new clinical development in AML

The European LeukemiaNet (ELN) 2017 risk classification is considered an essential guide for prognosis assessment in acute myeloid leukemia (AML) and to inform treatment decisions after patients achieve remission; however, only a few studies have validated its prognostic value in large patient populations.

Alex Bataller and colleagues1 have attempted to validate the ELN 2017 risk classification in patients with AML who were treated according to risk-adapted post remission therapy within the Spanish AML cooperative group Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias (CETLAM) protocol (CETLAM-12). Patients were retrospectively assigned to the corresponding ELN 2017 risk category and treatment outcomes were analyzed. The results were recently published in Blood Advances.1

CETLAM-12 treatment protocol is established for untreated, fit patients up to 70 years diagnosed with de novo AML and uses a similar risk stratification to the ELN 2017; favorable risk characteristics are the same and there are a few differences in intermediate and adverse-risk groups (Table 1).

Table 1. Comparison of AML risk classifications by the ELN 2017 and CETLAM-12

 

ELN 2017

CETLAM-12

Favorable risk

t(8;21)(q22;q22); RUNX1-RUNX1T1

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

Biallelic mutated CEBPA

Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow

Intermediate-I risk

Mutated NPM1 and FLT3-ITDhigh

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

Intermediate-II risk

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

Cytogenetic abnormalities not classified as favorable or adverse

Cytogenetic abnormalities not classified as favorable or adverse

Adverse risk

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

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

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

abn(3q) excluding t(3;5)(q21-25;q31-35); inv(3)(q21q26)/t(3;3)(q21;q26)

5 or del(5q); -7; -17/abn(17p); Complex karyotype, monosomal karyotype

 

add(5q),del(5q),-5, -7, add(7q)/del(7q), 17/abn(17p); Complex karyotype, monosomal karyotype

 

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

t(9;22)(q34;q11) ; BCR-ABL1

Wild-type NPM1 and FLT3-ITDhigh

 

FLT3-ITDhigh with or without NPM1 mutation

Mutated RUNX1, ASXL1 or TP53

 

CETLAM, Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias; ELN 2017, The European LeukemiaNet 2017 risk classification

The risk-adapted post-remission strategy (following a 3 + 7 induction regimen with idarubicin and cytarabine) in the CETLAM-12 protocol is summarized below:

  • Favorable risk group
    • Consolidation therapy: 3 courses of HDAC
    • BM MRD assessment: After chemotherapy course and thereafter at 3-month intervals for at least 3 years after CR
    • Allogeneic stem cell transplantation (allo-SCT): in case of a confirmed molecular failure
    • Transplant-ineligible patients: HMA or clinical trial
  • Intermediate and adverse-risk groups
    • Consolidation therapy: At least 1 course of HDAC
    • Patients with persistent minimal residual disease (MRD) post-consolidation allocated to high-risk category and allo-SCT was recommended.
    • Patients with FLT3 mutations could receive midostaurin within an early access program

Visual abstract

Below, we provide a visual abstract to summarize key outcomes by the ELN 2017 risk classification as well as a subset of patients with a poor prognosis within the ELN 2017 adverse-risk group.


Download this visual abstract

Click here to download this visual abstract

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  1. Bataller A, Garrido A, Guijarro F, et al. European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol. Blood Adv. 6(4):1193-1206. DOI:10.1182/bloodadvances.2021005585

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