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Cancer. 2019 Mar 15;125(6):873-883. doi: 10.1002/cncr.31874. Epub 2018 Dec 6.

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

Yoon JH1,2, Min GJ1, Park SS1, Jeon YW1, Lee SE1,2, Cho BS1,2, Eom KS1,2, Kim YJ1,2, Kim HJ1,2, Min CK1,2, Cho SG1,2, Kim DW1,2, Lee JW1,2, Lee S1,2.

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Department of Hematology, Catholic Hematology Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
Leukemia Research Institute, College of Medicine, Catholic University of Korea, Seoul, Korea.



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.


Philadelphia chromosome; acute lymphoblastic leukemia; minimal residual disease; reduced-intensity conditioning; tyrosine kinase inhibitor


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