Impact of ABO Mismatch on Outcomes of Allogeneic Hematopoietic Stem Cell Recipients: 30 Years of Experience with 1016 Patients
Authors: Atilla Erden , Topcuoglu Pervin , Akkus Erman , Ataca Atilla Pinar , Civriz Bozdag Sinem , Kurt Yuksel Meltem , Demirer Taner , Özcan Muhit , Beksac Meral , Ilhan Osman , Akan Hamdi , Arslan Onder , Gurman Gunhan , Toprak Selami Kocak 
Published: October 2019

Abstract
Introduction:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant and non-malignant hematological diseases. The impact of ABO mismatch on outcome following transplantation remains controversial. In this study, our aim is to define effects of ABO mismatch on engraftment, graft vs host disease, relapse free survival (RFS) and overall survival (OS) in patients who underwent allo-HSCT.
Patients and Methods:
Between 1988 and 2016, we retrospectively identified 1016 patients who underwent allo-HSCT at Ankara University School of Medicine, Department of Hematology. Chi-square and Fisher's exact tests were used where appropriate in comparison. Cox regression model and Kaplan Meier curves were applied for survival analysis. P<0.05 was considered as statistically significant.
Results:
The median follow-up period was 34.7 months (range, 0.2-229). In our cohort, there were 420 (41.3%) ABO-mismatched transplants occurred including 167 (16.4%) major, 197 (19.4%) minor and 55 (5.4%) bidirectional mismatches. The pre-transplant characteristics of patients are summarized in table. Allo-HSCTs from unrelated donors and peripheral blood grafts were detected higher in ABO mismatched patients vs ABO matched patients (28% vs 11%, P<0.0001; 78% vs 67%, P<0.0001). The engraftment failure was higher in ABO mismatch group compared to ABO matched group (67 (16%) vs 70 (11%), P=0.05). Neutrophil and platelet engraftment rates were not statistically different in major, minor or bidirectional ABO mismatched vs matched donors. The acute graft vs host disease (GVHD) and chronic GVHD incidences did not alter in patients with ABO match and mismatch (44% vs 45%, P=0.78; 41% vs 39%,P=0.81). In ABO-mismatched group, hemolysis after infusion of graft occurred in 50 patients (12%) whereas during engraftment in 35 patients (8%). Although not statistically significant, hemolysis were occurred higher in major ABO mismatch. Plasma exchanges were performed in 18 patients in the major ABO mismatched group due to high anti-donor type isoagglutinin titers (≥1/128). Pure red cell aplasia was diagnosed in 5 (3%) major ABO mismatched patients. Major ABO mismatch (HR:1.46, 95% Cl:1.06-2.03;P=0.022) was found to be related with lower RFS and OS (HR:1.31, 95% Cl:1.06-1.62;P=0.013). 3-year OS and 1-year RFS were lower with major ABO mismatch (38% vs 47%, P=0.02; 15% vs 24%; P=0.02) (Figure).
Conclusion:
Engraftment failure was detected higher in patients with ABO mismatch as well as major ABO mismatch was related with lower RFS and OS although the cohort is heterogeneous. Close monitoring and early treatment strategies for expectable complications would reduce the number fatal events by ABO mismatched allo-HSCT.

Disclosures
Civriz Bozdag: NOVARTIS: Consultancy; MSD: Research Funding; TAKEDA: Consultancy. Özcan:Abbvie: Other: Travel payment; Bayer: Research Funding; MSD: Other: travel support, Research Funding; Roche: Honoraria, Research Funding; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Novartis: Research Funding; Jazz: Other; Jazz: Other: Travel support; Archigen: Research Funding; Celgene: Other: Travel support, Research Funding; MSD: Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding. Beksac:Deva: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ilhan:Roche: Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau.