Impact of Graft Cell Dose on Outcomes after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide-Based Gvhd Prophylaxis

We aimed to investigate the impact of CD34+ graft cell dose on outcomes following haplo peripheral blood stem cell (haplo-PBSC) with post-transplant cyclophosphamide (PT-Cy)-based graft-versus-host disease ( GVHD) prophylaxis . In this retrospective study, we included all patients undergoing haplo-PBSCT (n=266) from 2013 to 2018 in the publicly available Center for International Blood and Marrow Transplant (P-5737 dataset, Ustun et al). Outcomes included overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS). Cox proportional hazard regression analyses were performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05. We included 266 patients who received a Haplo-PBSCT with PT-Cy-based GVHD prophylaxis. The graft cell dose was categorized as low dose (LD): 0-2 million CD34+ cells/kg (8%, n=22), intermediate-dose (ID): over 2 to 5 million CD34+ cells/kg (31%, n=82), and high dose (HD): over 5 million CD34+ cells/kg (61%, n=162) CD34+ cells/kg. Median OS was 2.85 years (LD: 0.53 yrs, 95%CI 0.30-0.87; ID: 2.46 yrs, 95% CI 0.63-Not reached/NR; HD: 4.48 yrs, 95% CI 1.94-NR). Median DFS was 0.95 years (LD: 0.37 yrs, 95% CI 0.20-0.77; ID: 1.21 yrs, 95% CI 0.63-NR; HD: 1.05 yrs; 95% CI 0.61-2.44). Median GRFS was 0.25 years (LD: 0.20 yrs, 95% CI 0.07-0.40; ID: 0.24 yrs, 95% CI 0.13-0.38; HD: 0.26 yrs; 95% CI 0.22-0.39). No statistically significant differences were noted in the incidence of relapse, grade II-IV acute GVHD, or chronic GVHD between the two groups. Adjusted multivariate regression analyses showed that graft cell dose of over 2 to 5 million cells/kg was associated with significantly superior OS (HR 0.34, 95% CI 0.18-0.63, p=0.001), superior DFS (HR 0.35, 95%CI 0.19-0.64, p=0.001), lower relapse risk (HR 0.17, 95% CI 0.07-0.39, p<0.001). At the same time, no significant association was observed with GRFS, NRM, grade II-IV acute GVHD, or chronic GVHD. In adjusted multivariate regression analyses, graft cell dose of over 5 million cells/kg was associated with significantly superior OS (HR 0.31, 95% CI 0.17-0.55, p<0.001), superior DFS (HR 0.38, 95% CI 0.22-0.65, p<0.001), superior GRFS (HR 0.57, 95% CI 0.34-0.96, p=0.033), and lower relapse risk (HR 0.24, 95% CI 0.12-0.51, p<0.001). At the same time, no significant association was observed with NRM, grade II-IV acute GVHD, or chronic GVHD. Higher CD34+ graft cell dose leads to improved outcomes after haploidentical peripheral blood stem cell transplantation. The data strongly supports the use of over 2 million CD34+ cells/kg, with the optimal cell dose potentially exceeding 5 million CD34+ cells/kg, to achieve superior survival and lower relapse rates.