Minimal residual disease-based long-term efficacy of reduced-intensity conditioning versus myeloablative conditioning for adult Philadelphia-positive acute lymphoblastic leukemia.

Abstract

The sensitivity of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) to reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) versus myeloablative conditioning (MAC) allogeneic HCT by minimal residual disease (MRD) kinetics is not well established. This study compared long-term outcomes based on MRD kinetics for 79 patients with RIC transplants and 116 patients with MAC transplants in first complete remission (CR1) after tyrosine kinase inhibitor-based chemotherapy (median follow-up, 67.1 months). MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction for all patients. RIC showed a cumulative incidence of relapse (CIR; 30.6% vs 31.7%), nonrelapse mortality (17.5% vs 14.9%), disease-free survival (DFS; 51.9% vs 53.4%), and overall survival (61.1% vs 61.4%) comparable to those associated with MAC. In all MRD kinetics-based subgroups, no differences in CIR (early complete molecular response [CMR], 19.3% vs 4.8%; early major molecular response [MMR], 17.0% vs 26.8%; late CMR, 20.0% vs 14.3%; late MMR, 28.3% vs 31.0%; poor molecular response [PMR], 57.9% vs 62.4%) or DFS (early CMR, 71.6% vs 76.2%; early MMR, 66.9% vs 52.1%; late CMR, 50.0% vs 64.3%; late MMR, 50.7% vs 53.7%; PMR, 31.6% vs 34.1%) were observed between RIC and MAC. In a multivariate analysis, the conditioning intensity had no significant impact on transplantation outcomes. RIC is a valid alternative choice for long-term disease control and is worthy of further investigation in prospective trials for adult Ph-positive ALL in CR1.