Red Blood Cell Allo-Antibodies after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Beerlage Astrid , Halter Joerg , Gerull Sabine , Medinger Michael , Ruefli Tanja , Stussi Georg , Heim Dominik , Drexler Beatrice , Infanti Laura , Holbro Andreas , Passweg Jakob R. , Buser Andreas S. 
Published: October 2019

Abstract
Introduction
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) may require red blood cell (RBC) transfusions. AB0 blood group barrier is the clinically most important RBC group in transfusion medicine and HSCT and patients always receive AB0 compatible RBC transfusions. Some patients however develop allo-antibodies against minor RBC antigens. To date there is only limited information about the specificity, immuniser and risk factors for the development of RBC allo-antibodies. In this retrospective single centre study we aimed to identify specificities, risk factors and clinical significance of the development of RBC allo-antibodies in HSCT patients.
Methods
In this study, we examined the occurrence of RBC alloantibodies in all consecutive patients treated with allogeneic HSCT at the University Hospital Basel between 1996 and 2017 receiving RBC transfusions. RBC and PLT components were all leukocyte depleted. As of 2012, all PLT components were pathogen reduced using the Intercept Blood system. AB0 and extended RBC typing of donor/ recipient pairs, the total number of RBC transfusions and their blood group typing (AB0 and extended RBC antigen typing when available) and the detection of RBC allo-antibodies were analysed and related to clinical outcome parameters.
Results
1314 donor/ recipient pairs were analysed. 110 (13%) of patients developed RBC allo-antibodies, 66 patients (5%) prior to HSCT, and 103 (8%) developed the first RBC allo-antibody after HSCT. 8 patients (0.6%) with an RBC allo-antibody before HSCT developed further RBC allo-antibodies after HSCT. Most patients developed only one RBC allo-antibody but in single patients up to 6 antibodies could be detected. The median time between HSCT and the detection of the antibody was 61 days, corresponding to the phase of the most intensive immunosuppressive treatment. In 60% of the patients developing RBC allo-antibodies after HSCT, the antibody was neither directed against the stem cell donor nor the recipient. In these cases, immunization occurred most likely by RBC transfusion. Anti-Rhesus-group antibodies are the most common antibodies (57%).
>10 RBC transfusions and the development of GvHD were risk factors for the development of antibodies. There was no significant difference in the occurrence of RBC allo-antibodies between donor type (related vs. unrelated), age or sex of the recipient.
Only few patients showed significant haemolysis in the period of the detection of the antibody. The direct antiglobulin test (DAT) was positive in 66% of the cases. Haemolysis defined as an increase of bilirubin, LDH or reticulocytes and a haemoglobin drop of more than 10 g/l could only be reported in 6% of the cases with antibodies detected.
The development of RBC allo-antibodies per se has no effect on the survival of patients (1y-survival 70±3% (without antibody) versus 68 ± 9%). However, evidence of haemolysis (even without drop of haemoglobin) in the context of allo-antibodies, is associated with significantly worse survival (1y- survival 75 ± 10% versus 42 ± 20%).
Conclusion
Allo-Antibodies after HSCT significantly contribute to the difficulties in transfusion management of these patients. Formation of RBC allo-antibodies is not frequent, but patients showing haemolysis after the development of an RBC allo-antibody show decreased survival. Most RBC allo-antibodies appear to be induced by RBC transfusion rather than by minor blood group mismatching between donor/ recipient pairs.

Disclosures
Heim: Novartis: Research Funding.