Mapping Donor Access for HSCT: Related, Haploidentical, and Unrelated Options in a Portuguese HLA Cohort

Introduction: Timely donor identification remains a major step in allogeneic hematopoietic stem cell transplantation (HSCT). However, donor availability depends on the donor source, family workup, HLA matching threshold, and population-background representation in donor registries. We assessed donor access in a Portuguese HLA referral cohort using related and unrelated donor data.

Methods: We performed a retrospective observational analysis of fully anonymized patient, relative, and unrelated donor datasets from January 2021 to May 2026. HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 were harmonized at high-resolution two-field level. The fixed cohort included 924 patients with complete six-locus data. Related donor availability was assessed at 12/12, ≥10/12, and probable haploidentical levels. Unrelated donor availability was assessed at 8/8, ≥7/8, 10/10, ≥9/10, 12/12, and ≥11/12 thresholds. HLA-DPB1 impact and exploratory prediction models were also evaluated.

Results: In the full cohort, 185 patients (20.0%) had a 12/12 related donor, 202 (21.9%) had a ≥10/12 related donor, and 595 (64.4%) had a probable haploidentical related donor. Among 653 patients with at least one complete evaluated relative, these values increased to 28.3%, 30.9%, and 91.1%, respectively. Unrelated donor availability was 13.1% for 8/8, 48.5% for ≥7/8, 12.8% for 10/10, 36.5% for ≥9/10, 2.9% for 12/12, and 12.4% for ≥11/12. HLA-DPB1 inclusion reduced strict unrelated matching more markedly than related matching. Prediction models showed moderate discrimination for several donor-availability targets, but weak performance for rare strict 12/12 unrelated availability.

Conclusions: Donor availability should be reported as a donor-access profile rather than as a binary result. Family workup, probable haploidentical options, unrelated donor thresholds, HLA-DPB1, and registry representation all influence realistic HSCT donor access.