The processing of stem cell concentrates from the bone marrow in ABO-incompatible transplants: how and when.

Abstract

An overview of ABO-incompatibility in haematopoietic stem cell transplantation Red blood cell (RBC) incompatibility in allogeneic haematopoietic stem cell transplantation (HSCT) may be classified into two main categories: major ABOincompatibility and minor ABO-incompatibility. Major ABO-incompatibility is defined as the expression of ABO-antigens on the donor's red cells, which are not present on the recipient's red cells. The recipient possesses antibodies and/or is capable of making antibodies against the donor's RBC antigens (e.g., a group A donor and a group O recipient). Minor ABO-incompatibility is defined as the expression of ABO antigens on the recipient's red cells that are not present on the donor's red cells. The donor's immune system is activated to make antibodies against the recipient's RBC antigens (e.g., group O donor and a group A recipient). Bidirectional ABO incompatibility between donor and recipient is defined as the presence of both major and minor barriers (e.g., donor type A, recipient type B)1. Furthermore, in allogeneic HSCT, donor and recipient pairs may also differ for other RBC antigens not belonging to the ABO system. Despite this, in the clinical field, the major focus of blood cell-incompatible transplantation has been on the ABO system because of the consequences of acute haemolysis resulting from the infusion of incompatible RBC or plasma, the delayed haemolytic reactions that may occur as a result of viable passenger lymphocytes infused as a component of the allograft and the delayed RBC recovery resulting from persistent host isoagglutinins directed against donor RBC2. The inheritance of blood group antigens is independent of the human leucocyte antigen (HLA) complex, the driving force in allogeneic stem cell transplantation. In addition, it is known in literature that upwards of 30% of allogeneic haematopoietic progenitor cell transplants from related donors and over 50% of transplants from unrelated donors will involve ABO-disparate donor and recipients2. Incompatibility of blood group antigens is, however, not a barrier to stem cell transplantation although it may have potentially serious consequences2-4. The ABO antigens are not clinically important targets of graft rejection or graft-vs-host disease in bone marrow transplantation. Moreover, the incidences of successful engraftment, graft rejection, and graft-vs-host disease are generally unaffected by ABO compatibility. These concepts were outlined by Gale et al. more than 30 years ago5. But is all the foregoing really true? Some authors have suggested that differences in ABO blood group between donor and recipient can in fact play a role in graft rejection and overall survival6,7. In addition, observational studies have highlighted that donors and recipients who are non-identical for both antigens and antibodies (e.g., a group A transplant to a group B recipient) may have increased treatment-related mortality8. In contrast, one study found that ABO non-identical transplants were associated with reduced relapse rates and improved overall survival in patients with acute leukaemia, and the mechanism hypothesised by the authors was more potent graft-vs-leukaemia effects in ABO non-identical transplants9. Obviously these are only examples to indicate that further studies are needed to clarify these aspects. In any case, it is well reported in the literature that major ABO-incompatible transplants, on which this review will focus, do carry the risk of a haemolytic transfusion reaction at the time of the bone marrow infusion due to the presence of incompatible donor RBC contained in the marrow inoculum10. In particular, ABO-incompatible recipients have circulating isoagglutinins directed against antigens on donor RBC which create a risk of haemolysis during and after marrow infusion11. Drawing conclusions, although ABO incompatibility between donor and recipient does not represent a barrier to successful HSCT12, it is well established that major ABO incompatibility can lead to prolonged destruction of donor-derived erythrocytes, with pure RBC aplasia and prolonged transfusion requirements13. In addition, minor ABO incompatibility can result in an increased risk of delayed immune haemolysis14,15, which occurs in approximately 10-15% of cases16. After this introduction, it should be noted that this review will focus on major ABO-incompatibility.