Gender Disparities in Allograft Access Due to HLA-Sensitization in Multiparous Women:Implications for Evaluation of Female Patients for Alternative Donor Transplantation

• Published in: Transplantation and cellular therapy 2024-02, Vol.30 (2), p.S22-S23
• Main Authors: Fingrut, Warren Benjamin, Davis, Eric, Archer, Anne, Brown, Samantha, Devlin, Sean M., Chinapen, Ms. Stephanie, Scaradavou, Andromachi, Politikos, Ioannis, Blouin, Amanda G, Shaffer, Brian C., Barker, Juliet
• Format: Article
• Language: English
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.12.064

The relationship between allograft patient (pt) demographics & HLA-antibody (Ab) burden, & the degree to which HLA-Ab burden impacts chosen donor type in the era of “donors for all”, is not established. We examined associations between pt sex/ parity, ancestry, & HLA-Ab burden in consecutive adult allograft recipients (excluding HLA-identical siblings) with acute leukemia, MDS, or MPN, transplanted 1/2016-12/2022. We also assessed the impact of HLA-Ab burden on donor type received. We classified HLA-Ab burden by the number & intensity of class I & II HLA-Abs. We hypothesized that multiparous females have the greatest HLA-Ab burden, potentially limiting provision of mismatched donors, especially given the haploidentical (haplo) graft rejection risk. Of 672 pts, 366/672 (54%) received 8/8 unrelated donor (URD) & 306/672 (46%) HLA-mismached grafts [137 cord blood (CB), 89 haplo, & 80 5-7/8 URD (mmURD)]; females [278/672 (41%)] were 54/278 (19%) nulliparous, 52/278 (19%) uniparous & 172/278 (62%) multiparous. Pt ancestry did not associate with HLA-Ab burden. Pt sex/ parity & HLA-Ab burden associations are shown in Fig. 1 & 2A. Overall, 254/672 (38%) pts had a positive screen & 140/672 (21%) were broadly &/or highly sensitized with 90/672 (13%) being both broadly & highly sensitized. Compared with males & nulliparous females, uni- & multi-parous female pts had > 2x the proportion of positive screens & > 8x the proportion broadly & highly sensitized (both p < .001). Among HLA-disparate graft recipients, compared with CB & mmURD recipients, fewer haplo recipients had positive screens (p = .024) & less than half the proportion (7/89, 8% vs 37/217, 17%) were broadly & highly sensitized (p = .038), Fig. 2B. Also, haplo recipients included the fewest multiparous females (16/89, 18%). Over 10% of transplanted pts were broadly & highly sensitized, with the HLA-Ab burden mostly in parous females. Pts with a high HLA-Ab burden were least likely to receive haplos & thus multiparous females received less haplos. These data have immediate implications: given HLA-Abs should be expected among parous females, in the absence of a matched adult donor, mmURDs or CB may need to be considered over haplos. This could compound allograft access for multiparous female pts of non-European heritage, given many lack a fully matched adult donor & face greatly decreased URD availability. At initial allograft evaluation, transplant centers should obtain ancestry & parity histories & screen f