Association between Prior Cytotoxic Therapy, Antecedent Hematologic Disorder, and Outcome after Allogeneic Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia.

(1) Background: Secondary acute myeloid leukemia (AML), i.e., AML arising from prior therapy (therapy-related) and/or an antecedent hematologic disorder (AHD) is generally associated with worse outcomes compared to de novo AML. However, recognizing the prognostic importance of genetic characteristics rather than clinical history, secondary AML is now considered a diagnostic qualifier rather than a separate disease entity. (2) Methods: To assess the association between clinical history and AML outcomes in the context of allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed 759 patients with de novo AML, 115 with AHD AML, and 105 with therapy-related AML who received first allografts while in first or second remission. (3) Results: At the time of HCT, these three cohorts differed significantly regarding many patient and disease-specific characteristics, including age (p < 0.001), gender (p < 0.001), disease risk (p = 0.005), HCT-CI score (p < 0.001), blood count recovery (p = 0.003), first vs. second remission (p < 0.001), remission duration (p < 0.001), measurable residual disease (MRD; p < 0.001), and conditioning intensity (p < 0.001). Relative to patients with de novo AML, relapse rates were similar for patients with AHD (hazard ratio [HR] = 1.07, p = 0.7) and therapy-related AML (HR = 0.86, p = 0.4) after multivariable adjustment, as were relapse-free survival (HR = 1.20, p = 0.2, and HR = 0.89, p = 0.5) and overall survival (HR = 1.19, p = 0.2, and HR = 0.93, p = 0.6). Non-relapse mortality was higher for AHD AML (HR = 1.59, p = 0.047). (4) Conclusions: These data suggest that the clinical history by itself contains limited prognostic value for adults with AML undergoing allografting, supporting the most recent approach to use this information as a diagnostic qualifier rather than a disease entity.