Introduction

Peripheral blood (PB) grafts are a well-known risk factor for graft-versus-host disease (GVHD) in nearly all hematopoietic cell transplantation (HCT) scenarios compared to bone marrow (BM) grafts. However, the impact of PB grafts remains uncertain within the context of posttransplant cyclophosphamide (PTCy)-based prophylaxis involving matched (MUD) and mismatched unrelated donors (MMUD). Our goal was to compare PB with BM grafts in this setting.Methods

This registry-based cohort study included patients who underwent hematopoietic cell transplantation in the United States between 2017 and 2021. Data were obtained from a Center for International Blood and Marrow Transplant Research (CIBMTR) registry database (Shaffer et al, DOI: 10.1200/JCO.24.00184). We included patients diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome who underwent HCT using MUD or MMUD with PTCy. The exposure was PB graft, and the control group was BM. The primary outcomes were relapse-free survival (RFS) and moderate/severe chronic GVHD (mod/sev cGVHD). Secondary outcomes included overall survival (OS), relapse (REL), non-relapse mortality (NRM), and grades II-IV and III-IV acute GVHD (aGVHD II-IV and aGVHD III-IV). Univariable analyses were conducted using log-rank and Gray tests for survival and cumulative incidence outcomes, respectively, while multivariable analyses employed cause-specific Cox models. Multivariable models were built based on the lowest Akaike Information Criterion. Two propensity score-based models confirmed the results of the multivariable analysis. All analyses were performed with R, R Foundation for Statistical Computing, Vienna, Austria, Version 4.1.1.Results

With a median follow-up of 31 months, 2,065 patients received PB and 229 received BM from MMUDs. In the MUD group, RFS (HR=0.86, 95% CI: 0.66–1.12, p=0.26) and cGVHDms (HR=1.59, 95% CI: 0.74–3.43, p=0.24) did not differ between PB and BM. Patients undergoing PB HCT were older (median 62 vs 56 years), were less likely to receive a myeloablative regimen (38% vs 54%), and an HLA 8/8 donor was more frequent than an HLA 7/8 donor (75% vs 55%), compared with BM. Most PB transplants were performed in the more recent years, unlike BM. Other patients' characteristics were relatively well balanced.

PB did not impact OS (HR = 0.87, 95% CI 0.69-1.09, p = 0.22), RFS (HR = 0.86, 95% CI 0.70-1.06, p = 0.15), relapse (HR = 0.85, 95% CI 0.66-1.1, p = 0.23), NRM (HR = 0.99, 95% CI 0.70-1.41, p = 0.97), grades II-IV aGVHD (HR = 1.05, 95% CI 0.81-1.36, p = 0.70), grades III-IV aGVHD (HR = 1.34, 95% CI 0.74-2.43, p = 0.33), or moderate to severe cGVHD (HR = 1.33, 95% CI 0.85-2.09, p = 0.21).

In the MUD group, OS (HR = 0.87, 95% CI 0.65-1.18, p = 0.37) and moderate to severe cGVHD (HR = 1.59, 95%CI 0.74-3.43, p = 0.24) were not different between PB and BM. In the MMUD group, PB and BM OS (HR = 0.90, 95%CI 0.64-1.28, p = 0.57) and moderate to severe cGVHD (HR = 1.24, 95%CI 0.70-2.19, p = 0.47) were not different.

The results of the PS-based Cox models were not different.Discussion

This study found no significant differences in clinical outcomes between BM and PB grafts in MUD or MMUD transplants using PTCy-based GVHD prophylaxis. These findings are noteworthy, given the longstanding perception of PB as a higher-risk graft for GVHD. The historical dilemma—where PB offers a more convenient collection process for donors (Burns et al, DOI: 10.1016/j.bbmt.2016.02.018) and physicians, but BM was believed to ensure better recipient outcomes—may not apply to unrelated donors with PTCy-based GVHD prophylaxis. These data support prioritizing the donor's preferences for graft source in the unrelated donor setting, without compromising patient safety and HCT outcomes.Acknowledgments

This study received no external funding. The authors declare no conflict of interest.

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2025
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