Validation of the ELN 2017 risk stratification for acute myeloid leukemia

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

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

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.