Red Cell Alloimmunization Rates in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Introduction: Donor selection for allogeneic hematopoietic stem cell transplant (allo-HSCT) is dependent on matching with the intended recipient HLA allele profile, but not blood group compatibility. Red blood cell (RBC) phenotype matching is not considered, even if recipient alloantibodies are present pre-HSCT. Historically, up to 3.7% of allo-HSCT recipients have been found to develop new RBC alloantibodies following allo-HSCT. We completed an audit of all adult and pediatric allo-HSCT recipients of the Alberta Bone Marrow and Blood Cell Transplant Program to define the rate of RBC alloimmunization, and evaluate the impact of this RBC alloantibody presence on donor marrow engraftment in our allo-HSCT recipient population.

Methods:A retrospective review was completed including all allogeneic pediatric and adult HSCT recipients between January 1, 2007 and January 1, 2015. Data was obtained from review of cellular therapy laboratory electronic records with red cell alloantibody information extracted manually from the transfusion medicine laboratory information system.

Results: A total of 674 patients, including 104 pediatric recipients (<18 years old), underwent 697 allo-HSCT procedures (591 peripheral blood, 45 marrow, 61 cord blood). The mean HSCT recipient age was 40 (range 0-66) and most common HSCT indication was acute myeloid leukemia. Myeloablative conditioning was given to all adults and 86% of pediatric recipients. Fully HLA matched grafts were provided to 77% of recipients. ABO compatibility status of allo-HSCT procedures included the following: 362 (52%) ABO identical grafts, 154 (22%) grafts with a minor incompatibility, 143 (21%) grafts with a major incompatibility, and 38 (5.0%) grafts with bidirectional incompatibility. Rh mismatches were present in 165 (24%) of donor-recipient pairs.

A total of 47 allo-HSCT recipients, including 3 pediatric and 44 adult patients, were found to have RBC alloantibodies before or after allo-HSCT. A total of 45 (6.4%) of allo-HSCT recipients had detectable RBC alloantibodies pre-HSCT, with 69 individual alloantibodies identified. The most common RBC alloantibody was anti-E (30%). Antibody screen results available on the day of or following HSCT in 43 allo-HSCT recipients found: 12 (28%) with antibody disappearance pre-HSCT and a negative screen on the date of allo-HSCT, 15 (35%) with antibody waning to disappearance after allo-HSCT, and 11 (26%) with persistence of pre-HSCT antibodies following allo-HSCT. New post-HSCT RBC alloantibodies were detected in 3 adult recipients of peripheral blood collected stem cell grafts (anti-D; anti-Kpa; anti-K plus anti-E), with an overall rate of 0.4%. These patients all received myeloablative conditioning and grafts which were ABO identical or had a minor ABO incompatibility. The anti-D antibody developed post-transplant in an Rh positive recipient of an Rh negative graft. Thus, the calculated overall rate of anti-D development in Rh mismatched HSCT recipients was 0.6%. There was no observed impact on neutrophil and platelet engraftment comparing adult allo-HSCT recipients who did and did not have pre-HSCT RBC alloantibodies.

Conclusion: The risk of post-HSCT RBC alloantibody development is very low, even in Rh mismatched donor-recipient pairs. ABO incompatibility does not affect the risk of post-HSCT alloantibody development. Allo-HSCT recipients infrequently have pre-HSCT RBC alloantibodies, which may disappear after myeloablative conditioning. The presence of RBC alloantibodies pre-HSCT does not appear to impact donor marrow engraftment. The results of our retrospective study are limited by the availability, timing and frequency of post-HSCT antibody screen investigations. The decision to perform an antibody screen post-HSCT is a clinical one, typically dependent on recipient transfusion needs. Further prospective research is required to more accurately determine the rate of new post-HSCT alloantibody development and duration of alloantibody persistence or disappearance in allo-HSCT recipients. Results of these studies may also help guide RBC transfusion decisions in HSCT recipients known to have pre-HSCT RBC alloantibodies with proven engraftment and a negative post-HSCT antibody screen.