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

Background: The selection of an optimal graft source in haploidentical hematopoietic cell transplantation (haplo HCT) is an area of debate. Previous studies have reported comparable survival with a bone marrow (BM) or peripheral blood stem cells (PBSC) graft with a lower rate of chronic graft-versus-host disease (GVHD) and higher quality of life with BM and a lower relapse rate and faster engraftment with PBSCs; however, current literature is heterogeneous. We aimed to investigate the outcomes following BM versus PBSC haplo HCT using posttransplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis.

Methods: We conducteda retrospective multicenter analysis, including haplo 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. We examined 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). 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 550 patients who received haplo-HCT with PT-Cy-based GVHD prophylaxis. The median age was 59.8 years, and 62% (n=345) were male. The graft source was peripheral blood in 62.5% (n=344) and bone marrow in 37.5% (n=206) of patients. The primary hematologic malignancies included acute myeloid leukemia (AML) in 54% (n=297), acute lymphoblastic leukemia (ALL) in 17% (n=91), and myelodysplastic syndrome (MDS) in 29% (n=158). Ethnicities were Caucasian (63.5%, n=349), African American (20%, n=108), Hispanic (9.5%, n=52), and Asian and others (7%, n=41). The conditioning regimen was myeloablative in 38% (n=207) of patients. The Karnofsky performance score was 90% or higher in 47% (n=257) of patients. The Hematopoietic cell transplantation-specific comorbidity index of less than three was noted in 50% (n=274) of patients. Median follow-up time was 3.83 (95% CI 3.17-3.94) years. A lower risk of relapse (39% PBSC vs. 49% BM, p=0.017) and higher incidence of chronic GVHD (38% PBSC vs 22% BM, p<0.001) was observed in PBSC as compared to BM graft recipients. No statistically significant differences were noted in OS (Median years: 2.44 PBSC vs. 1.97 BM), DFS (Median years: 0.90 PBSC vs. 0.81 BM), GRFS (Median years: 0.26 PBSC vs. 0.38 BM), and grade II-IV acute GVHD (37% PBSC vs. 32% BM) between the two groups. In the adjusted multivariate regression analyses adjusted for significant correlates, the use of PBSC vs. BM graft was associated with a lower GRFS (HR 1.23, 95% CI 1.00-1.51, p=0.04) and a higher incidence of chronic GHVD (HR 2.87, 95% CI 1.78-4.63, p<0.001). No significant differences were observed in OS (HR 1.37, 95% CI 0.96-1.95, p=0.081), DFS (HR 1.13, 95% CI 0.80-1.58, p=0.496), NRM (HR 1.32, 95% CI 0.86 - 2.04, p=0.200), and grade II-IV acute GVHD (HR 1.21, 95% CI 0.87-1.68, p=0.256) with the use of PBSC compared to BM graft.

Conclusion: In patients undergoing haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide-based GVHD prophylaxis, we found that recipients of peripheral blood stem cell grafts had a higher incidence of chronic GVHD and slightly lower GVHD-free relapse-free survival compared to those with bone marrow grafts. However, regardless of the graft source, there were similar overall and disease-free survival rates, relapse, non-relapse mortality, and acute GVHD.

Mushtaq:Iovance Biotherapeutics: Research Funding. McGuirk:NEKTAR therapeutics: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; Autolus: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy.