Comparison of Myeloablative versus Reduced-Intensity Conditioning Regimens in Allogeneic Stem Cell Transplantation Recipients with Acute Myelogenous Leukemia with Measurable Residual Disease-Negative Disease at the Time of Transplantation: A Retrospective Cohort Study

Abstract

The ideal conditioning intensity in allogeneic hematopoietic stem cell transplantation (HSCT) is evolving. Previous prospective studies comparing myeloablative conditioning (MAC) versus reduced-intensity conditioning (RIC) regimens in adults with acute myelogenous leukemia (AML) have shown mixed results. In many of these studies, patients were not stratified based on measurable residual disease (MRD). We evaluated the effect of conditioning intensity on the outcomes of AML patients in complete remission (CR) with flow cytometry evidence of MRD negativity. A total of 135 patients age 20 to 75 years with AML in CR1 or CR2 and flow cytometry evidence of MRD negativity who underwent allogeneic HSCT at our center between 2011 and 2019 were evaluated. We compared overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD) in recipients of MAC (n = 89) and RIC (n = 46). Although the patients receiving RIC were older (62 versus 51 years; P < .0001), there were no statistically significant differences between the groups in terms of Eastern Cooperative Oncology Group and European Leukemia Network risk criteria and disease status (CR1 or CR2) at the time of transplantation. At a median follow-up of 24.6 months, no statistically significant differences in OS (hazard ratio [HR], 0.78; 95% confidence interval [CI] 0.42 to 1.42, P = .411) or RFS (HR, 1.004; 95% CI, 0.48 to 2.09, P = .99) were identified. The cumulative incidence of NRM (HR, 0.595; 95% CI, 0.24 to 1.48; P = .2644) and relapse (HR, 1.007; 95% CI, 0.45 to 2.23; P = .9872) was not different between the 2 groups. Grade II-IV and grade III-IV acute GVHD were more frequent in the MAC group (39.3% verses 19.9% [P = .018] and 19.3% versus 2.3% [P < .001], respectively), as was moderate/severe chronic GVHD (23.6% versus 15.8%; P = .038). Our data indicate that conditioning intensity did not appear to affect OS, RFS, NRM, and relapse risk in patients with MRD-negative AML as measured by flow cytometry. RIC resulted in less severe acute and chronic GVHD.

Keywords: AML; Allogeneic; Flow cytometry; Minimal residual disease; Myeloablative; Reduced-intensity conditioning; Stem cell.