Pure red cell aplasia of long duration complicating major ABO- incompatible bone marrow transplantation [see comments]

Abstract

In 3 of 15 consecutive patients receiving a human leukocyte antigen (HLA)-identical but major ABO incompatible bone marrow transplant (BMT), pure red cell aplasia (PRA) lasting 5 to 8 months was observed. Titers of the incompatible anti-A agglutinin before infusion of the red blood cell (RBC)-depleted BMT was very high in one, and in the usual range in two patients. Decrease of agglutinin titers during the first 4 weeks after BMT were comparable between PRA patients and those of ABO- incompatible BMT recipients with timely RBC recovery. However, in PRA patients, agglutinin titers rose again and remained elevated for 19 to 28 weeks. RBC engraftment and reticulocyte recovery ultimately occurred spontaneously and coincided with the decrease of agglutinin titers below 16. These observations indicate that PRA is antibody-dependent in this setting. Furthermore, it is conceivable that cyclosporine facilitates recipient-derived antibody synthesis after major ABO- incompatible BMT.

Regeneration of erythropoiesis after related‐ and unrelated‐donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems

“…We observed PRCA exclusively after major ABO‐incompatible BMT, which is in line with previously published reports 1–8 . A PRCA incidence of 15 to 20 percent has been reported in various series of patients given stem cell grafts from HLA‐matched, major ABO‐incompatible siblings 1–8 …”

“…Inhibition of the growth of RBC precursors in the marrow inoculum seems to be the mechanism of RBC aplasia. Whether high pre‐transplant hemagglutinin titers are associated with PRCA is still controversial 1–3,6,8,16 . We did not observe a correlation between pretransplant hemagglutinin titers and the occurrence of PRCA in our patients.…”

“…Because the inheritance of blood group antigens is independent of the HLA antigen complex, 1 ABO incompatibility between donor and recipient exists in about 20 percent of HLA‐matched allogeneic or unrelated bone marrow or peripheral blood HPC donor–recipient pairs, but blood group incompatibility does not appear to determine the outcome of BMT in terms of incidence of graft rejection or delayed WBC and platelet engraftment 2–5 . Nevertheless, in a minority of major ABO‐incompatible bone marrow recipients, prolonged reticulo‐cytopenia and an increased transfusion requirement were observed 6–9 . This report describes seven patients after major ABO‐incompatible BMT or peripheral blood HPC transplant who developed pure RBC aplasia (PRCA); the clinical follow‐up and various treatment modalities are reported.…”

“…There is general agreement that hemagglutinins are responsible for the occurrence of PRCA in patients undergoing major ABO‐incompatible BMT 1,2,4,8 . Inhibition of the growth of RBC precursors in the marrow inoculum seems to be the mechanism of RBC aplasia.…”

Safety and impact of donor‐type red blood cell transfusion before allogeneic peripheral blood progenitor cell transplantation with major ABO mismatch

“…This phenomenon is attributed to host isoagglutinins that are directed not only toward mature marrow‐derived RBCs but also against erythroid precursors with the features of the ABO system. This phenomenon can culminate in PRCA that is characterized by long‐lasting reticulocytopenia (more than 60 days) and absence of RBC precursors in the marrow 21,22 . Irrespective the regular transfusion of RBCs, treatment of PRCA after major ABO‐mismatched PBPCT can be difficult, and several treatment options are described, for example, plasma exchange or change of immunosuppressive therapy including tapering to induce graft‐versus‐host disease (GVHD) 23‐26 …”