Abstract
Background:
Post-transplant cyclophosphamide (PTCy) has emerged as a prevalent strategy for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) and bone marrow (BM) represent established graft sources, albeit with differing immunological implications. The study aims to evaluate outcomes associated with PBSC versus BM to better comprehend the effects of graft selection in allo-HCT recipients using matched unrelated donors (MUD).
Methods:
A retrospective multicenter analysis was conducted on allo-HCT patients who underwent MUD transplant (2017-2021) using PTCy-based-GVHD-prophylaxis using publicly accessible P5891 dataset from Center for International Blood and Marrow Transplant Research (CIBMTR) by Shaffer et al. Patients were stratified by stem cell source into PBSC and BM groups. Outcomes assessed included overall survival (OS), clinical relapse, non-relapse mortality (NRM), grade II–IV and III–IV acute GVHD, and moderate/severe chronic GVHD (cGVHD). Univariable and multivariable Cox proportional hazards or Fine-Gray competing risks models were used as appropriate. Variables with p < 0.1 in univariable analysis and clinically relevant factors were included in multivariable models. Analyses were performed using Python 3.9.15 and R 4.4.2.
Results: A total of 1,673 adult patients were included in the analysis. The median age was 62 years (IQR, 50–68), with 52% male. PBSC was the graft source in 92.4% of cases (n= 1546). The underlying diagnoses were acute myeloid leukemia (54.2%) and myelodysplastic syndromes (31.0%). At time of transplant, 51.3% were in first complete remission (CR1), and 56.8% were classified as intermediate risk by disease risk index (DRI). PBSC recipients were significantly older (median 62 vs. 58 years; p < 0.01), more likely to receive reduced-intensity or non-myeloablative conditioning (62% vs. 41%; p < 0.01), and more frequently had CMV seronegative donor/recipient pairs (27% vs. 21%; p = 0.034). A Karnofsky Performance Status (KPS) score below 90 was documented in 44.8% of patients, and 52.0% had a Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score of 3 or higher. At a median follow-up of 35.1 months, 3-year overall survival was similar between PB and BM recipients (59.1% vs. 59.5%, p = 0.89). In univariable cox analysis, graft source was not significantly associated with OS (HR 0.95; 95% CI, 0.71–1.27; p = 0.739), clinical relapse (HR 0.90; 95% CI, 0.64–1.25; p = 0.520), or NRM (HR 0.95; 95% CI, 0.61–1.47; p = 0.830). These findings remained consistent in multivariable analysis with OS (HR 0.87; 95% CI, 0.64–1.18; p = 0.376), clinical relapse (HR 0.90; 95% CI, 0.63–1.28; p = 0.558), NRM (HR 0.81; 95% CI, 0.51–1.29; p = 0.384), moderate/severe cGVHD (HR 1.55, 95% CI 0.72–3.32, P=0.259), grade II–IV aGVHD (HR 0.95, 95% CI 0.68–1.32, P=0.742) and grade III–IV aGVHD (HR 0.81, 95% CI 0.39–1.7, P=0.582). Several non-graft covariates during multivariate analyses were independently associated with survival outcomes. A comorbidity index ≥3 (HR 1.35; 95% CI, 1.15–1.61; p < 0.001), Karnofsky score <90 (HR 1.22; 95% CI, 1.04–1.44; p=0.017), high DRI (HR 2.15; 95% CI, 1.17–3.97, p=0.014) and very high DRI (HR 5.04; 95% CI, 2.27–11.21, p<0.001) were significantly associated with inferior OS. Additionally, patients receiving non-myeloablative (HR 1.42; 95% CI, 1.06–1.88, p=0.0173) and those with high DRI (HR 2.66; 95% CI, 1.24–5.67, p=0.012) and very high DRI (HR 4.96; 95% CI, 1.8–13.63, p=0.002) had an increased risk of relapse.
Conclusion: In matched unrelated donor allo-HCT with PTCy-based GVHD prophylaxis, graft source was not associated with differences in overall survival, relapse, or non-relapse mortality. While peripheral blood stem cell recipients were older and more likely to receive reduced-intensity conditioning, graft source had no significant impact on long-term outcomes. These findings suggest that graft choice may be individualized, guided by institutional preference or logistical considerations and provide flexibility in graft source selection without a compromise in efficacy.
