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

Abstract

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. Li et al. Pre-MRD on Ph + ALL Outcomes 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.

Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…Indeed, engraftment was better following PBSC compared to BM in the HaploSCT group. In agreement with some of the previous publications the incidence of aGVHD and severe aGVHD was higher following HaploSCT compared with MSD transplants [13,14], while other publications comparing HaploSCT to MSD transplants in ALL have reported a similar incidence of aGVHD [16,17]. As previously reported, female donors to male patients and center effect were associated with a higher rate of aGVHD [29].…”

“…equivalent results between HaploSCT and alloSCT from MSD in patients with ALL, but moreover a reduced relapse rate, stronger graft-versus leukemia (GVL) effect, and superior attainment of measurable residual disease (MRD) negativity in HaploSCT compared with alloSCT in patients with ALL [16][17][18]. We therefore aimed, in the current study, to compare the outcomes of HaploSCT with those from MSD transplants in ALL, using the ALWP/EBMT registry.…”

Association of minimal residual disease with clinical outcomes in Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A systemic literature review and meta-analysis

“…209 records were discarded for the following reasons: not investigating the correlation between MRD and outcomes (n = 166), including non-TKIs treated patients (n = 7), less than 50 patients (n = 15), insufficient data to attain HRs and 95% CIs (n = 10), overlapped cohorts (n = 11). Finally, 27 records were included in the qualitative analysis [ 7 , 9 , 11 , 17 – 40 ]. The study selection process is summarized as a flow chart in Fig 1 .…”

Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy—The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group

“…An optimal solution that would combine available methods, TKIs, chemotherapy, and SCT in children with ALL Ph+ is still being sought. Monitoring of MRD levels, evaluated by flow cytometry and/or PCR test, during and at the end of the induction phase of therapy is useful for assessing treatment response and making SCT decisions [ 11 , 12 , 13 , 14 ].…”