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. 2025 Aug 12;9(15):4023-4036.
doi: 10.1182/bloodadvances.2025016236.

Outcomes of haploidentical vs mismatched unrelated donor HCT with posttransplant cyclophosphamide prophylaxis

Yosra M Aljawai  1 , Jeremy Ramdial  1 , Gabriela Rondon  1 , Portia Smallbone  1 , Partow Kebriaei  1 , Uday Popat  1 , Betul Oran  1 , Katayoun Rezvani  1 , Richard E Champlin  1 , Elizabeth J Shpall  1 , Rohtesh S Mehta  1
Affiliations

Outcomes of haploidentical vs mismatched unrelated donor HCT with posttransplant cyclophosphamide prophylaxis

Yosra M Aljawai et al. Blood Adv. .

Abstract

Limited data exist comparing haploidentical and mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) with posttransplantation cyclophosphamide for graft-versus-host disease prophylaxis, especially considering donor age. Herein, we report the outcomes of 660 haploidentical and 195 MMUD HCT recipients treated at MD Anderson Cancer Center. Beyond standard Cox proportional hazards modeling, we used inverse probability of treatment weighting (IPTW) and matched-pair analysis, and performed additional analysis by incorporating an external MMUD validation cohort from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary outcome was overall survival (OS). In multivariable analysis, haploidentical donors had a hazard ratio (HR) of 1.20 (95% confidence interval [CI], 0.93-1.54; P = .16) compared with the MMUD group. Donor age showed a nonlinear association with OS. These findings were corroborated by IPTW, matched-pair analyses, and CIBMTR validation analyses. Exploratory analysis revealed inferior OS for older (age of >50 years) haploidentical donor group compared with younger (age of <30 years) MMUD recipients (HR, 1.91; 95% CI, 1.21-3.01; P = .005). Our analyses suggest that although donor type may play a role, there was a more prominent role for donor age in influencing OS. Moreover, our findings indicate a potential nuance wherein the impact of donor type may vary by donor age. Further research, particularly with larger cohorts, is needed to fully elucidate the complex and potentially interacting roles of donor type and donor age, along with HLA factors.

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Conflict of interest statement

Conflict-of-interest disclosure: K.R. and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical and Affimed GmbH. K.R. participates on the scientific advisory board for Avenge Bio, Virogin Biotech, Navan Technologies, Caribou Biosciences, Bit Bio Limited, Replay Holdings, oNKo-innate, the Alliance for Cancer Gene Therapy, Innate Pharma, and Shinobi Therapeutics; and is the scientific founder of Syena. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier estimate of OS comparing Haplo donor (yellow line) and MMUD (blue line) groups. Haplo, haploidentical.
Figure 2.
Figure 2.
Effect of donor age on OS. The nonlinear effect of donor age on OS is visualized using a natural spline from a Cox PH multivariate model (adjusted covariates shown in Table 2), with HRs plotted relative to a donor age of 34 years (median donor age).
Figure 3.
Figure 3.
Kaplan-Meier estimate of OS comparing Haplo donor and MMUD groups, further categorized by donor age (<30 years, 30-50 years, and >50 years).
Figure 4.
Figure 4.
NRM and relapse by donor type. Cumulative incidence of NRM (A) and relapse (B) comparing Haplo donor (yellow line) and MMUD (blue line) groups.
See this image and copyright information in PMC

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