Upfront comprehensive donor search overcomes the impact of poor search prognosis, irrespective of racial background

Abstract

Abstract Introduction: Access to suitably matched donors remains a major barrier to allogeneic hematopoietic cell transplantation (HCT), particularly for non-White patients, who are underrepresented in global donor registries. Traditional donor search strategies vary in timing and resource intensity, often leading to delays or exclusion in racially diverse populations. At the Leukemia/BMT Program of British Columbia, which serves a multiethnic population under a publicly funded healthcare system, we implemented a strategy of simultaneous related and unrelated donor searches at diagnosis. This contrasts with the sequential, prognosis-guided approach supported by the recent BMT CTN 1702 trial. We hypothesized that early, comprehensive donor evaluation may mitigate the negative impact of poor donor search prognosis and lead to more equitable transplant access and outcomes across racial groups.  Methods: We conducted a single-centre retrospective study of 542 consecutive adult patients with hematologic malignancies undergoing donor search between 2020–2024. Patients were categorized by self-identified race: White (n=401), Asian (n=107), and Other (n=34). Both transplanted and non-transplanted patients were analyzed. The primary endpoint was overall survival (OS); secondary endpoints included donor search prognosis (https://search-prognosis.b12x.org), donor availability, final donor type, time to HCT in acute leukemia patients in first complete remission (CR1), and 1-year HCT outcomes of non-relapse mortality (NRM), relapse incidence (RI), progression free survival (PFS). Statistical analyses included Kaplan-Meier survival curves, log-rank tests, and cumulative incidence for competing risks. Results: Despite differences in donor availability, transplantation rate were similar across groups (White: 70%, Asian: 74%, Other: 59%; p=0.9). Good donor search prognosis was significantly more common in White patients (57%) than in Asian (37%) and Other (10%) patients (p<0.0001). Availability of fully matched unrelated donors (MUD) also differed significantly (White: 76%, Asian: 59%, Other: 40%; p=0.0002). Non-White patients more frequently received alternative donors, especially haploidentical grafts (White: 9%, Asian: 24%, Other: 25%, p=0.001). Importantly, very few patients were unable to proceed to transplant due to donor unavailability (1 per group). Median time to HCT for acute leukemia in CR1 was comparable across races (Whites: 128 days, Asian: 127 days, Other: 135 days, p=0.4). One-year overall survival showed a statistically significant difference (White: 80%, Asian: 85%, Other: 50%; p=0.03), while relapse incidence (White: 10%, Asian: 14%, Other: 30%; p=0.1), non-relapse mortality (White: 12%, Asian: 4%, Other: 20%; p=0.3), and progression-free survival (White: 74%, Asian: 85%, Other: 60%; p=0.4) were not significantly different. Conclusion: In a public funded healthcare setting with centralized transplant coordination, a strategy of simultaneous donor search at diagnosis was associated with equitable transplant access and comparable transplant timing across racial groups, despite underlying differences in donor availability. While overall survival was lower in patients of other racial backgrounds, no statistically significant differences in relapse or non-relapse mortality suggest that the early search approach may mitigate traditional donor-related barriers. This model offers a promising alternative to sequential donor search algorithms and warrants further evaluation in diverse health systems.