Impact of CD34+ Graft Cell Dose on Outcomes after Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide-Based Gvhd Prophylaxis

Background: CD34+ graft cell dose might impact outcomes after haploidentical bone marrow transplantation (Haplo BMT) with post-transplant cyclophosphamide (PT-Cy)-based graft versus host disease (GVHD) prophylaxis. We aimed to investigate the effect of graft cell dose on the outcomes after Haplo BMT with PT-Cy-based GVHD prophylaxis.

Methods: A retrospective multicenter analysis was conducted, including Haplo- BMT recipients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. We examined the impact of graft cell dose on post-transplant outcomes, including overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), grade II-IV acute GVHD, chronic GVHD, and GVHD-free relapse-free survival (GRFS). Patient-, disease- and transplant-related factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox proportional hazards regression analyses were used for OS, DFS, GRFS, NRM, acute and chronic GVHD, and relapse outcomes. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. A significance level of 0.05 was used throughout. Statistical analyses were conducted using Stata version 18.

Results: We included 173 haplo BMT recipients with PT-Cy-based GVHD prophylaxis. The median age was 62 years (interquartile range 50.7-68), and 61% (n=106) of patients were male. Ethnicities were Caucasian (68%, n=117), African American (16%, n=28), Hispanic (11%, n=19) and others (5%, n=9). Ninety patients (52%) had a Karnofsky performance score of 90% or higher, and 47% (n=81) had a comorbidity index of 3 or higher. Hematologic diagnoses included acute myeloid leukemia (51%, n=89), acute lymphoblastic leukemia (16%, n=28), and myelodysplastic syndromes (31%, n=54). Myeloablative and reduced-intensity conditioning were performed in 25% (n=43) and 75% (n=130) recipients respectively. Growth factor was used in 84% (n=145) of patients. The graft cell dose was 2 million or less CD34+ cells/kg (35%, n=60) and over 2 million CD34+ cells/kg (65%, n=113). The median follow-up time was 4.01 (95% CI 3.39-4.31) years. The median OS, DFS, and GRFS were 1.97 years (95% CI 1.4-4.31), 0.84 years (95% CI 0.67-1.30), and 0.39 years (95% CI 0.30-0.50), respectively. In haplo BMT recipients receiving a graft cell dose of >2 million CD34+ cells/kg as compared to ≤2 million CD34+ cells/kg, no statistically significant differences were noted in OS (Median years: 1.91 vs. 2.04), DFS (Median years: 0.81 vs. 0.86), GRFS (Median years: 0.33 vs. 0.44), relapse (50% vs. 48%), acute GVHD (32% vs. 28%), or chronic GVHD (22% vs. 20%). After adjusting for significant variables in the multivariate regression models, use of higher graft cell dose (over 2 million CD34+ cells/kg) did not show any significant differences in OS (HR 0.98, 95% CI 0.62-1.56, p=0.0.932), DFS (HR 1.01, 95% CI 0.65-1.58, p=0.964), GRFS (HR 1.09, 95% CI 0.72-1.64, p=0.680), relapse (HR 1.15, 95% CI 0.68-1.94, p=0.601), NRM (HR 0.79, 95% CI 0.31-2.03, p=0.622), acute GVHD (HR 0.9, 95% CI 0.47-1.72, p=0.741), and chronic GVHD (HR 1.15, 95% CI 0.57-2.33, p=0.703).

Conclusion: Our study did not find a significant association between graft cell dose and haploidentical bone marrow transplantation outcomes with post-transplant cyclophosphamide-based GVHD prophylaxis. It is feasible to successfully perform haploidentical bone marrow transplantation with a graft cell dose of less than 2 million CD34+ cells/kg.