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

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.3759-3759
• Main Authors: Fingrut, Warren B, Davis, Eric, Archer, Anne, Brown, Samantha, Devlin, Sean M., Chinapen, Stephanie, Scaradavou, Andromachi, Politikos, Ioannis, Blouin, Amanda, Shaffer, Brian C., Barker, Juliet N
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-180416

Introduction: The relationship between allograft patient (pt) demographics & HLA-antibody (HLA-Ab) burden, & the degree to which HLA-Ab burden impacts donor type received in the current era of “donors for all”, is not established. Methods: 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 1/2018-12/2022. 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 (HLA-A, B, -C) & II (HLA-DR, -DQ, -DP) HLA-Abs. A mean fluorescence intensity (MFI) > 1,000 defined a positive HLA-Ab. Pts were classified as broadly sensitized (more than the median number of class I/ II HLA-Abs among Ab positive pts) &/or highly sensitized (MFI > 10,000 for ≥ 1 HLA-Ab). For pts with > 1 screen, the one closest to transplant was used. We hypothesized that multiparous females have the greatest HLA-Ab burden, limiting provision of haploidentical (haplo) grafts in these pts due to the rejection risk. Results: Of 672 pts [median age 60 yrs (range 29-79), 419/672 (62%) with acute leukemia, 472/672 (70%) with European ancestry], 278/672 (41%) were female of whom 54/278 (19%) were nulliparous, 52/278 (19%) uniparous & 172/278 (62%) multiparous. Overall, 367/672 (55%) received 8/8 unrelated donor (URD) & 305/672 (45%) HLA-disparate grafts [137 cord blood (CB), 88 haplo, & 80 5-7/8 URD (mmURD)]. As expected, non-European pts received 2x the proportion of HLA-disparate grafts [165/472 (35%) vs 141/200 (70%), p < .001]. Pt ancestry was not associated with HLA-Ab burden. Pt sex/ parity & HLA-Ab burden associations are shown in Table 1A & Fig. 1. Over one third [254/672 (38%)] of pts had a positive screen for class I/ II HLA-abs (median of 8 HLA-Abs of positive pts, range 1-113). In the 254 positive pts, 3,563 Abs were detected with the MFI distribution being 1,001-4,000 in 1,340/3,563 (38%), 4,001-10,000 in 874/3,563 (25%) & > 10,000 in 1,349/3,563 (38%). Of the total pt cohort, 140/672 (21%) pts 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 over 2x the proportion of positive screens [117/448 (26%) vs 137/224 (61%), p < .001]. They also had more than 8x the proportion broadly & highly sensitized [17/448 (4%) vs 73/224 (33%), p < .001]. HLA-Ab burden