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Validation of the ELN 2017 risk stratification for acute myeloid leukemia
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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.
- 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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