Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL
Siqi Li, Qiao‐Zhen Fan, Lan‐Ping Xu, Yu Wang, Xiaohui Zhang, Huan Chen, Yu‐Hong Chen, Feng‐Rong Wang, Wei Han, Yuqian Sun, Chen‐Hua Yan, Feifei Tang, Yanrong Liu, Xiao‐Dong Mo, Xinyu Wang, Kai‐Yan Liu, Xiao‐Jun Huang, Ying‐Jun Chang
Abstract
Background: This study compared the effects of pretransplantation measurable residual disease (pre-MRD) on outcomes in Philadelphia chromosome (Ph)-positive ALL patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical SCT (haplo-SCT). Methods: A retrospective study (n=202) was performed. MRD was detected by real-time quantitative PCR. Results: In the total patient group, patients with positive pre-MRD had a higher 4-year cumulative incidence of relapse (CIR) than that in patients with negative pre-MRD (26.1% vs. 12.1%, P=0.009); however, the cumulative incidence of nonrelapse mortality (NRM) (7.4% vs. 15.9%, P=0.148), probability of leukemia-free survival (LFS) (66.3% vs. 71.4%, P=0.480), and overall survival (OS) (68.8% vs. 76.5%, P=0.322) were comparable. In the MSDT group, patients with positive pre-MRD had increased 4-year CIR (56.4% vs. 13.8%, P<0.001) and decreased 4-year LFS (35.9% vs. 71.0%, P=0.024) and OS (35.9% vs. 77.6%, P=0.011) compared with those with negative pre-MRD. In haplo-SCT settings, the 4-year CIR (14.8% vs. 10.7%, P=0.297), NRM (7.3% vs. 16.3%, P=0.187) and the 4-year probability of OS (77.7% vs. 72.3%, P=0.804) and LFS (80.5% vs. 75.7%, P=0.660) were comparable between pre-MRD positive and negative groups. In subgroup patients with positive pre-MRD, haplo-SCT had a lower 4-year CIR (14.8% vs. 56.4%, P=0.021) and a higher 4-year LFS (77.7% vs. 35.9%, P=0.036) and OS (80.5% vs. 35.9%, P=0.027) than those of MSDT. Multivariate analysis showed that haplo-SCT was associated with lower CIR (HR, 0.288; P=0.031), superior LFS (HR, 0.283; P=0.019) and OS (HR, 0.252; P=0.013) in cases with a positive pre-MRD subgroup. Conclusions: Our results indicate that the effects of positive pre-MRD on the outcomes of patients with Ph-positive ALL are different according to transplant modality. For Ph-positive cases with positive pre-MRD, haplo-SCT might have strong graft-versus-leukemia (GVL) effects.