Stem cell transplantation

A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study

Abstract

Relapse is a major cause of treatment failure in Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to evaluate the effect of a new pre-emptive tyrosine kinase inhibitors (TKIs) strategy on relapse in Ph+ALL patients with complete remission undergoing allo-HCT. Pre-emptive TKIs initiation was based on BCR/ABL molecular monitoring. TKIs choice was based on BCR/ABL mutations. Donor lymphocyte infusion was recommended in those with poor response to TKIs. Prophylactic TKIs from historical data were as control. The primary endpoint was relapse. One hundred and sixty-seven Ph+ALL patients were enrolled in this study, including 103 in the pre-emptive group and 64 in the prophylactic group. The 3-year cumulative incidence of relapse was 11% and 31% in the pre-emptive and prophylactic groups (P = 0.001), respectively. The 3-year overall survival (OS) was 87% and 66% (P = 0.001), and leukemia-free survival (LFS) was 83% and 61% (P = 0.000), respectively, in the pre-emptive and prophylactic groups. Multivariate analysis showed that the pre-emptive strategy was the protective factor for relapse, OS, and LFS (P = 0.005, P = 0.005, and P = 0.003, respectively). Our data suggest that this new pre-emptive TKIs strategy based on BCR/ABL molecular monitoring might reduce relapse and improve survival for Ph+ALL patients undergoing allo-HCT. ClinicalTrials.Gov Identifier (NCT01883219).

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Fig. 1: Consolidated Standards of Reporting Trials (CONSORT) diagram.
Fig. 2: Relapse and survival after transplantation.
Fig. 3: The incidence of GVHD after transplantation.

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Acknowledgements

We thank Pro. Robert Gale (Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College, London, UK) and Pro. Michael Andreeff (Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA) for offering expert advice. We thank all the faculty members that participated in these studies. This work was supported by the National Key Research and Development Programme of China (Grant Nos. 2017YFA105500, 2017YFA105504), the National Natural Science Foundation of China (Nos. 81770190, 81700176, 81500149, 81401315), Science and Technology Planning Project of Guangdong Province (2019B020236004), Project of the Zhujiang Science and Technology Star of Guangzhou City (No. 201806010029), Natural Science Foundation of Guangdong Province (No. 2019A1515011924), the Science and Technology Program of Guangzhou City (201707010213), and the Clinical Research Project of Nanfang Hospital, Southern Medical University (LC2016ZD009).

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Liu, H., Xuan, L., Lin, R. et al. A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study. Leukemia (2020). https://doi.org/10.1038/s41375-020-01090-4

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