Depth of Response to Intensive Chemotherapy Has Significant Prognostic Value among Acute Myeloid Leukemia (AML) Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation with Intermediate or Adverse Risk at Diagnosis Compared to At-Risk Group According to European Leukemia Net 2017 Risk Stratification.

Abstract

Simple SummaryAcute myeloid leukemia (AML) is a devastating but potentially curable disease. The updated version of the European Leukemia Net (ELN) 2017 genetic risk stratification is used as the standard for the prognosis and classification of AML. In the present study, we evaluated the prognostic value of the ELN 2017 criteria on post-hematopoietic stem-cell transplantation (HSCT) outcomes and compared it with pre-HSCT measurable residual disease (MRD) status, determined by Wilms tumor gene 1 (WT1) expression. We classified the patients as intermediate (INT) risk and adverse (ADV) risk. We found that the ELN 2017 risk classification did not effectively predict post-HSCT outcomes in patients with INT or ADV risk. The pre-HSCT WT1 level predicted post-HSCT relapse better than ELN 2017 and had a more prominent prognostic value in the ELN INT risk group than in the ADV risk group.We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n = 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p < 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.