Outcomes after Bone Marrow Versus Peripheral Blood Matched Sibling Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide-Based Gvhd Prophylaxis

Background: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for various hematologic disorders. Choosing an optimal graft source, bone marrow (BM) versus peripheral blood stem cells (PBSC), plays a crucial role in transplantation outcomes. We aimed to compare the outcomes following BM versus PBSC grafts in patients undergoing matched sibling donor (MSD) HCT with posttransplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis.

Methods: A retrospective multicenter analysis was conducted, including MSD HCT recipients with PT-Cy-based GVHD prophylaxis in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. The impact of graft source 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) was examined. 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 performed. 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. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05.

Results: We included 315 MSD HCT recipients receiving PT-Cy-based GVHD prophylaxis. The median age was 48.9 years, and 59% (n=187) were male. The graft source was peripheral blood in 70.5% (n=222) and bone marrow in 29.5% (n=93) of patients. The primary hematologic malignancies included acute myeloid leukemia (AML) in 55% (n=169), acute lymphoblastic leukemia (ALL) in 25% (n=76), and myelodysplastic syndrome (MDS) in 20% (n=63). Ethnicities were Caucasian (65.5%, n=206), African American (16%, n=51), Hispanic (10.5%, n=33), and Asian and others (8%, n=25). The conditioning regimen was myeloablative in 52% (n=163) of patients. The Karnofsky performance score was 90% or higher in 55% (n=173) of patients. The Hematopoietic cell transplantation-specific comorbidity index of less than three was noted in 53% (n=166) of patients. Median follow-up time was 3.26 (95% CI 3.06-3.89) years. No statistically significant differences were noted in OS (Median years: 4.89 PBSC vs. Not reached BM), DFS (Median years: 1.35 PBSC vs. 1.68 BM), GRFS (Median years: 0.25 PBSC vs. 0.32 BM), relapse (43% PBSC vs. 41% BM), grade II-IV acute GVHD (38% PBSC vs. 35.5% BM), or chronic GVHD (40% PBSC vs. 29% BM). In the adjusted multivariate regression analyses adjusted for significant correlates, no significant differences were observed in OS (HR 1.19, 95% CI 0.69-2.05, p=0.528), DFS (HR 0.97, 95% CI 0.61-1.55, p=0.898), GRFS (HR 0.96, 95% CI 0.65-1.41, p= 0.825), relapse (HR 1.04, 95%CI 0.58-1.85, p=0.896), NRM (HR 1.45, 95% CI 0.71-2.98, p=0.309), and grade II-IV acute GVHD (HR 0.87, 95% CI 0.51-1.49, p=0.617), and chronic GVHD (HR 1.69, 95% CI 0.88-3.24, p=0.117) with the use of PBSC compared to BM graft.

Conclusion: The results of this study confirm that matched sibling donor peripheral blood stem cell or bone marrow transplantation leads to comparable outcomes, including overall survival, disease-free survival, GVHD-free relapse-free survival, relapse, non-relapse mortality, and acute and chronic GVHD, regardless of the graft source.