Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Research, adult, Clinical Practice (Health Services and Quality), health outcomes research, Clinical Research, genomics, immune mechanism, immunology, Biological Processes, Study Population, Human
Objective: We sought to compare the outcomes of T-cell replete haplo HCT using a mother vs father donor with PTCy prophylaxis, after accounting for (mis)matching at individual HLA loci and patient/donor age.
Results: We included 57 patients with a mother (n=29) vs father (n=28) donor. Median age at HCT (23 yrs vs 27 yrs, p=0.1) and donor age (50 yrs vs 52 yrs, p=0.9) were similar in both groups. Most received RIC (79% vs 86%, p=0.5), BM graft (83% vs 75%, p=0.5), had HCT-CI >3 (46% vs 64%, p=0.2), and low/intermediate DRI (45% vs 54%, p=0.8), were CMV seropositive (86% vs 79%, p=0.04), and B-leader matched (51% vs 48%, p=0.9) and ABO matched with the donor (76% vs 64%, p=0.4). The recipient was male in 59% (mother donor) vs 61% (father donor). The median follow-up was 54 vs 28 months.
Graft failure occurred in 0% vs 4%, p=0.3; the median time to neutrophil engraftment was 18 days in both groups. The cumulative incidence of grade II-IV aGVHD (65% vs 56%, p=0.3) and grade III-IV aGVHD at day 180 (31% vs 15%, p=0.2), 3-yr cGVHD (31% vs 15%, p=0.2); NRM (35% vs 26%, p=0.5), relapse (21% vs 32%, p=0.4), PFS (39% vs 36%, p=0.9) and OS was (53% vs 41%, p=0.3) in mother vs father donor, respectively.
In multivariate analysis, no statistically significant differences were noted in any outcome between mother vs father donors, likely due to small number of events. However, B-leader mismatch was associated with a significantly higher risk of NRM (HR 2.7, 95% CI 1.03-7.02, p=0.04), and HLA-A mismatch was associated with a lower risk of NRM (HR 0.3, 95% CI 0.1-0.8, p=0.02), better PFS (HR 0.2, 95% CI 0.1-0.4, p<0.001) and OS (HR 0.1, 95% CI 0.05-0.4, p<0.001). HCT-CI >3 was associated with inferior PFS (HR 3.5, 95% CI 1.5-7.6, p=0.002) and OS (HR 4.1, 95% CI 1.7-9.8, p=0.002).
Conclusion: HLA factors, such as B-leader mismatch (high NRM) and HLA-A mismatch (low NRM and high PFS and OS) may have a stronger prognostic impact on mortality than donor-relationship. Recognizing the limitations of the small sample size, our data suggest that among parent haplo donors, in cases where both father and mother are B-leader matched and/or HLA-A mismatched with the recipient, father should be preferred due to a 2-fold higher risk of grade III-IV aGVHD and cGVHD (although statistically non-significant) with maternal donors. However, it remains unclear whether a B-leader mismatched (and/or HLA-A matched) father be selected over a B-leader matched (and/or HLA-A mismatched) mother. Further large-scale studies are needed to comprehend these complex immunobiological relationships.
Disclosures: Mehta: Syndax: Research Funding; Orca Bio: Research Funding. Alousi: Incyte: Honoraria, Research Funding; Prolacta: Consultancy; Genetech: Consultancy; Mallinkrodt: Honoraria; Sanofi / Kadmon: Honoraria. Kebriaei: Ziopharm: Research Funding; Amgen: Research Funding; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nieto: Secura Bio: Research Funding; Affimed: Other: Scientific advisory Board, Research Funding; Astra Zeneca: Research Funding. Oran: AROG: Research Funding; ASTEX: Research Funding. Popat: Abbvie: Research Funding; Incyte: Research Funding; Bayer: Research Funding; Iovance: Consultancy; Novartis: Research Funding. Srour: Orca Bio: Research Funding. Rezvani: Caribou Biosciences: Other: Participates on the Scientific Advisory Board ; Navan Technologies: Other: Participates on the Scientific Advisory Board ; Bayer: Other: Participates on the Scientific Advisory Board ; GSK: Other: Participates on the Scientific Advisory Board ; Virogin Biotech: Other: Participates on the Scientific Advisory Board ; AvengeBio: Other: Participates on the Scientific Advisory Board ; GemoAb: Other: Participates on the Scientific Advisory Board ; Takeda: Patents & Royalties, Research Funding; Affimed: Research Funding. Champlin: Johnson &Johnson: Consultancy; Omeros: Consultancy; Kadmon: Consultancy; Actinium: Consultancy; General Oncology: Other: Data Safety Monitoring Board; Bluebird: Other: Data Safety Monitoring Board; Cell Source Inc.: Research Funding. Shpall: Navan: Consultancy; NY blood center: Consultancy; Affimed: Other: License agreement; axio: Consultancy; adaptimmune: Consultancy; Takeda: Patents & Royalties; Bayer: Honoraria; Fibroblasts and FibroBiologics: Consultancy.
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