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Background:  This study compared the effects of pre-transplantation 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 RT-PCR and multiparameter flow cytometry.   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 non-relapse 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-vs.-leukemia (GVL) effects.

frontiers in oncology

Different Effects of Pre-transplantation Measurable Residual Disease on Outcomes According to Transplant Modality in Patients With Philadelphia Chromosome Positive ALL