Primary Results From Blood and Marrow Transplant Clinical Trials Network 1702: Clinical Transplant-Related Long-Term Outcomes of Alternative Donor Allogeneic Transplantation
Lee SJ, Logan B, Horowitz MM, Dehn JG, et al. J Clin Oncol. 2025 Nov;43(31):3369-3380. doi: 10.1200/JCO-25-00206.
Comment by Alexander Kulagin, RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia.
This multicenter prospective biological assignment study (BMT CTN 1702) evaluated whether using a donor search prognosis score, predicting the likelihood of finding an 8/8 HLA-matched unrelated donor (MUD), affects survival and transplant outcomes. Based on HLA allele frequencies and race/ethnicity, patients were categorized as Very Likely (>90%), Less Likely, or Very Unlikely (<10%) to find a MUD. Those Very Unlikely were directed to proceed promptly HCT from alternative donors (mismatched unrelated (MMUD), haploidentical, or cord blood).
Among 1,751 evaluable patients, two-year overall survival from evaluability showed no significant difference between the Very Likely (n=958) and Very Unlikely (n=276) groups in both univariate (HR 1.00) and multivariate analyses (HR 1.07). The probability of proceeding to HCT was similar across groups (70%, 66%, and 62%, respectively), and the median time from patient evaluability to HCT was just over three months (ranging from 3.3 to 3.4 months), with no significant difference between the groups. Of 1,179 transplanted patients, MUD use was 94% in the Very Likely group versus only 9% in the Very Unlikely group in which most patients received grafts from haploidentical relatives (60%), MMUDs (23%), or cord blood (8%). Despite this disparity, no significant differences were observed in overall survival, relapse incidence, treatment-related mortality, disease-free survival, or acute and chronic GVHD among the groups, including in multivariate model.
The study concludes that a donor search prognosis strategy successfully prioritizes alternative donors for patients unlikely to find a MUD, yielding comparable survival and transplant outcomes.
Comment:
The BMT CTN 1702 study successfully shifts the paradigm from a sequential, donor-specific search to a prognosis-based strategy. This approach may improve access and equity, especially for patients from underrepresented racial/ethnic groups. Despite obvious differences from the European approach of searching for a 10/10 matched donor, the key findings of the study could be compelling if local predictive models of allele frequency and ethnic minority proportions are used. Further development requires comparing alternative donors in the context of modern GVHD prophylaxis and accounting for non-HLA factors like donor age and sex, which were not systematically considered in the current trial design.