A New Pre-Emptive Strategy for Preventing Relapse Based on BCR/ABL Monitoring for Ph+ ALL Undergoing Allo-HCT: A Retrospective Prophylactic TKIs Study and Prospective Validation in a Clinical Trial Cohort

Background: Relapse is a major cause of treatment-failure in patients with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Whether tyrosine kinase inhibitors (TKIs) used post-transplantation could reduce relapse remains controversial. In this study, a new pre-emptive strategy post-transplantation based on BCR/ABL monitoring was compared with prophylactic strategy for preventing relapse. Methods: One hundred and sixty-seven patients were enrolled in this study, including 103 in pre-emptive and 64 in prophylactic groups. The pre-emptive strategy was based on molecular monitoring of BCR/ABL levels and BCR/ABL mutations, and donor lymphocyte infusion was recommended in those who were not responsive to TKIs. The prophylactic TKIs strategy was based on TKI treatment pre-transplantation. The primary endpoint was relapse. Findings: The 3-year cumulative incidence of relapse post-transplantation was 11% and 34% in pre-emptive and prophylactic groups, respectively (P=0.000). The 3-year cumulative overall survival (OS) were 87% and 64% (P=0.000), and LFS were 83% and 58% (P=0.000), respectively, in pre-emptive and prophylactic groups. Multivariate analysis showed that pre-emptive strategy was the predictive factor for relapse, OS and LFS (all P=0.000). Interpretation: Our data suggests that this new pre-emptive strategy based on BCR/ABL monitoring could reduce relapse and improve overall survival for Ph+ALL patients undergoing allo-HCT compared with prophylactic TKIs. Trial Registration: ClinicalTrials.Gov Identifier (NCT01883219). Funding Statement: This work was supported by the National Key Research and Development Programme of China (Grant No.2017YFA105500, 2017YFA105504), the National Natural Science Foundation of China (No. 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), the Science and Technology Program of Guangzhou City (201707010213), and the Clinical Research Project of Nanfang Hospital, Southern Medical University (LC2016ZD009). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The protocol was reviewed and approved by the institutional review board of each of the participating centers and was conducted in accordance with the Declaration of Helsinki. Patients provided written consent before entering the study.