Long-Term Survival Gains after Allogeneic Hematopoietic Stem Cell Transplant are Driven by Reductions in Non-Relapse Mortality: A 35-Year Statewide Australian Cohort Study

Allogeneic hematopoietic stem cell transplant (alloHSCT) has evolved substantially in recent decades, expanding patient access via widespread adoption of increased age limits, alternate mismatched donors, reduced intensity conditioning, and novel graft-versus-host disease (GVHD) prophylaxis strategies. However, real-world outcomes reflective of these changes remain underreported. We performed a retrospective population-based analysis of all consecutive adult alloHSCT within South Australia from 1990 to 2023 (N = 864). Patients were grouped by decade to evaluate temporal changes in practice and outcomes. Median age at transplant increased from 41 yr in the 1990s to 54 yr in the 2020s, with patients aged ≥60 yr now comprising >40% of recipients. Donor utilization shifted markedly, with matched related donors declining (90% to 25%) in favor of matched unrelated (10% to 51%) and haploidentical donors (0% to 16%). Conditioning intensity transitioned from predominantly myeloablative (68% to 21%) to reduced intensity regimens (32% to 71%). Despite treating an older and more comorbid population, outcomes improved steadily: 3-yr overall survival increased from 41% in the 1990s to 58% in the 2020s (P = .0005), progression-free survival from 37% to 49% (P = .01), and non-relapse mortality (NRM) declined from 55% to 25% (P < .0001). Relapse rates remained static at approximately 26% to 31% since 2000, with disease status at transplant the strongest predictor of recurrence. GVHD incidence peaked in the 2010s but declined in the 2020s, coinciding with wider adoption of post-transplant cyclophosphamide. In conclusion, alloHSCT outcomes have improved markedly over 35 yr, with survival gains predominantly driven by reductions in NRM. Relapse remains the dominant barrier to cure, underscoring the need for novel strategies to augment disease control.