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

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

doi:10.1038/s41409-020-01129-1

Madlen Jentzsch, Sebastian Schwind + Show 8 more

Open Access

https://doi.org/10.1038/s41409-020-01129-1

Copy DOI

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.

Highlights

Since acute myeloid leukemia (AML) is a biologically and clinically highly heterogeneous disease, a reliable risk stratification is very important to personalize treatment strategies
Regarding patients in the outcome set, sAML patients more often received a NMA conditioning (P < 0.001), were more likely to receive their allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR)/ CR with incomplete peripheral recovery (CRi) (P = 0.03), more likely to have a CRi compared to a CR (P = 0.005), while we observed no difference in preHSCT MRD status between de novo and Secondary or therapy-related acute myeloid leukemia (s/tAML) patients (P = 0.78, Supplementary Table S3)
S/tAML patients had a different distribution of the European LeukemiaNet (ELN) risk groups compared to de novo disease and were more likely to harbor adverse ELN risk (P < 0.001 and P = 0.01, respectively, Fig. 1b), Outcome of s/tAML patients

Summary

Introduction

Since acute myeloid leukemia (AML) is a biologically and clinically highly heterogeneous disease, a reliable risk stratification is very important to personalize treatment strategies.

Methods

Results

Conclusion