ELN risk stratification and outcomes in secondary and therapy-related AML patients consolidated with allogeneic stem cell transplantation

Madlen Jentzsch, Juliane Grimm, Marius Bill, Dominic Brauer, Donata Backhaus, Karoline Goldmann, Julia Schulz, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind, Madlen Jentzsch, Juliane Grimm, Marius Bill, Dominic Brauer, Donata Backhaus, Karoline Goldmann, Julia Schulz, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind

Abstract

Secondary or therapy-related acute myeloid leukemia (s/tAML) differs biologically from de novo disease. In general s/tAML patients have inferior outcomes after chemotherapy, compared to de novo cases and often receive allogeneic stem cell transplantation (HSCT) for consolidation. The European LeukemiaNet (ELN) risk stratification system is commonly applied in AML but the clinical significance is unknown in s/tAML. We analyzed 644 s/tAML or de novo AML patients receiving HSCT. s/tAML associated with older age and adverse risk, including higher ELN risk. Overall, s/tAML patients had similar cumulative incidence of relapse (CIR), but higher non-relapse mortality (NRM) and shorter overall survival (OS). In multivariate analyses, after adjustment for ELN risk and pre-HSCT measurable residual disease status, disease origin did not impact outcomes. Within the ELN favorable risk group, CIR was higher in s/tAML compared to de novo AML patients likely due to a different distribution of genetic aberrations, which did not translate into shorter OS. Within the ELN intermediate and adverse group outcomes were similar in de novo and s/tAML patients. Thus, not all s/tAML have a dismal prognosis and outcomes of s/tAML after allogeneic HSCT in remission are comparable to de novo patients when considering ELN risk.

Trial registration: ClinicalTrials.gov NCT03904251 NCT04128748.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1. AML patients in the association…
Fig. 1. AML patients in the association set (n = 644).
a Distribution of disease origin and b distribution of the ELN risk groups according to disease origin.
Fig. 2. Outcome according to disease origin…
Fig. 2. Outcome according to disease origin (de novo vs secondary or treatment-related AML) for patients in the outcome set (n = 534).
a Cumulative incidence of relapse, b non-relapse mortality, and c overall survival in all patients.
Fig. 3. Outcome according to disease origin…
Fig. 3. Outcome according to disease origin (de novo vs secondary or treatment-related AML) for patients in the outcome set (n = 534) given separately for both conditioning regimens.
a Cumulative incidence of relapse, b non-relapse mortality, and c overall survival for patients receiving NMA-HSCT (n = 379) and d cumulative incidence of relapse, e non-relapse mortality, and f overall survival for patients receiving RIC- or MAC-HSCT (n = 155).
Fig. 4. Outcome and disease characteristics according…
Fig. 4. Outcome and disease characteristics according to disease origin (de novo vs secondary or treatment-related AML) within the separate ELN risk groups.
a Distribution of primary disease, b cumulative incidence of relapse, c overall survival, and d genetic associations in patients with favorable ELN risk, e distribution of primary disease, f cumulative incidence of relapse, g overall survival, and h genetic associations in patients with intermediate ELN risk and i distribution of primary disease, j cumulative incidence of relapse, k overall survival, and l genetic associations in patients with adverse ELN risk.

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Source: PubMed

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