Published on October 24, 2025
Outcomes of haploidentical vs. mismatched unrelated donor HCT with posttransplant cyclophosphamide prophylaxis
by Alex Kadhim
Researchers at MD Anderson Cancer Center have determined that donor age has a stronger, nonlinear impact on overall survival compared to donor type in allogeneic HCT using posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis, with donor type becoming increasingly relevant in older donors. The team analyzed 855 first transplants performed between 2008 and 2024, including 660 haploidentical and 195 mismatched unrelated donor (MMUD) procedures. Researchers applied multivariable Cox models, inverse probability of treatment weighting, and 1:2 propensity matching, as well as ran a validation analysis with an external MMUD cohort from a Center for International Blood and Marrow Transplant Research data set. Across methods, donor type alone did not significantly predict survival, while donor age showcased a clear association with mortality.
The study speaks to a common clinical problem, whereby many patients lack fully HLA matched donors, resulting in clinicians often choosing between a haploidentical relative and an MMUD. Historical concerns regarding MMUD toxicity were tied to calcineurin inhibitor regimens, but outcomes have improved with posttransplantation cyclophosphamide. Prior registry comparisons rarely accounted for donor age, a known prognostic factor. In this current study, donor age was modeled both as categories (<30, 30 to 50, >50 years) and with restricted cubic splines. Models adjusted for recipient age, disease and Disease Risk Index, conditioning intensity, graft source, HCT-CI, CMV serostatus, and sex mismatch, with proportional hazards issues handled by stratification.
Older donors consistently worsened outcomes, with donors aged greater than 50 years old exhibiting higher hazards for overall mortality (HR about 1.46 to 1.68) and nonrelapse mortality (HR about 1.55 to 2.14) compared with donors younger than 30, while relapse risk showed no clear age effect. Severe grade 3 to 4 acute GVHD rose approximately fivefold with older donors. In acute myeloid leukemia and myelodysplastic syndrome cases, haploidentical donors carried roughly 55 to 60 percent lower severe acute GVHD risk than MMUD, whereas chronic GVHD tracked with donor age rather than donor type. Exploratory comparisons suggest that older haplo donors fared worse than younger MMUD donors in terms of survival (HR 1.91, P=.005). Clinically, the data favor prioritizing younger donors and expanding searches to younger relatives or MMUD when only older haplo options exist.
Reference:
Aljawai YM, Ramdial J, Rondon G, et al. Outcomes of haploidentical vs mismatched unrelated donor HCT with posttransplant cyclophosphamide prophylaxis. Blood Adv. 2025;9(15):4023-4036.
http://doi.org/10.1182/bloodadvances.2025016236
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