Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

Abstract

BackgroundPersistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia. Design and MethodsWe investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipients with major ABO incompatibility. ResultsTwelve patients (8%) developed pure red cell aplasia, 3/98 (3%) with, and 9/55 (16%) without prior isoagglutinin reduction (p=0.009). Red blood cell engraftment was faster in patients with isoagglutinin reduction; in addition, peripheral blood hematopoietic stem cell transplantation, acute graft-versus-host disease, and younger age were associated with faster red blood cell engraftment in Cox regression analysis. In patients with pure red cell aplasia the mean red blood cell engraftment occurred after 225 days (p<0.001) and was associated with a simultaneous decrease of anti-donor isoagglutinins. Patients with pure red cell aplasia had higher pretransplant anti-donor isoagglutinin titers (p=0.001) and received more post-transplant red blood cell transfusions (p<0.001). ConclusionsFollowing major ABO incompatible hematopoietic stem cell transplantation, pure red cell aplasia and delayed red blood cell engraftment depend on the levels of anti-donor isoagglutinins and are efficiently prevented by the pretransplant removal of these isoagglutinins. The benefits of reducing the time of transfusion-dependency and transfusion-associated risks must be carefully balanced against the potential side effects of isoagglutinin reduction.Key words: ABO blood group incompatibility, allogeneic hematopoietic stem cell transplantation, pure red cell aplasia.Citation: Stussi G, Halter J, Bucheli E, Valli PV, Seebach L, Gmür J, Gratwohl A, Schanz U, Passweg JR, and Seebach JD. Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins. Haematologica 2009; 94:239-248. doi:10.3324/haematol.13356 ©2009 Ferrata Storti Foundation. This is an open-access paper.Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

Major ABO-incompatible BMT: isohemagglutinin reduction with plasma exchange is safe and avoids graft manipulation

“…In a review of 153 patients undergoing major or bidirectional ABO-incompatible BM (74%) or peripheral blood (26%) haematopoietic progenitor cell transplant, the incidence of PRCA was 3% in the patients who underwent isohemagglutinin reduction and 16% in the patients who did not (P ¼ 0.009). 25 The results of this study are consistent with this observation. The single case of PRCA occurred in a patient with very high titres of both anti-A and anti-B, despite both isohemagglutinin reduction and red cell depletion.…”

“…[22][23][24] The risk of PRCA following BMT is increased in patients with higher pre-transplant isohemagglutinin titres. 25 Furthermore, pretransplant isohemagglutinin reduction has been shown to effectively prevent PRCA. In a review of 153 patients undergoing major or bidirectional ABO-incompatible BM (74%) or peripheral blood (26%) haematopoietic progenitor cell transplant, the incidence of PRCA was 3% in the patients who underwent isohemagglutinin reduction and 16% in the patients who did not (P ¼ 0.009).…”

Red blood cell-incompatible allogeneic hematopoietic progenitor cell transplantation

“…78,[81][82][83][84][85] The incidence of PRCA is likely influenced by the degree of suppression of recipient B cells achieved by various factors including the intensity of the conditioning regimen, posttransplant immunomodulations such as rapid withdrawal of immunosuppressive medications and the occurrence of GvHD. Stussi et al 73 proposed pre-transplant plasmapheresis and post-transplant infusion of donor type RBCs to decrease the risk of developing PRCA by reducing the titer of anti-donor isoagglutinins after transplantation. Plasmapheresis is not a completely effective preventive strategy; it is possible for host anti-donor isoagglutinin titers to increase after transplantation.…”

“…15 Alternately, the risk of acute hemolytic reactions may be lessened by reduction of recipient isoagglutinin titers by plasma exchange or immunoadsorption, 15,72 by infusion of donor-type RBCs, 68 or combinations of both. 73 The reduction of recipient isoagglutinins by plasmapheresis or immunadsorption allows ABO-incompatible kidney (and other solid organ) transplantation, and has been used in conjunction with splenectomy or rituximab infusions to prevent post transplant rebound of isoagglutinin titers. 74,75 Multiple procedures are usually necessary and isoagglutinins may rebound rapidly after treatment requiring post-transplant plasmapheresis, as well.…”

Transfusion Support Issues in Hematopoietic Stem Cell Transplantation

“…43,55 Because PRCA is associated with high levels of isohemagglutinins, [44][45][46][47] a direct reduction of titers by plasma exchange may be effective in some patients. 47,56 Although the reduction of titers before the transplantation has been attempted to prevent PRCA, 57,58 knowing the actual effect of this approach is impossible. Some European centers use apheresis as standard care for reducing pretransplantation isohemagglutinin titers to fewer than 1:32.…”