Immune hemolysis involving non-ABO/RhD alloantibodies following hematopoietic stem cell transplantation

Abstract

Summary:We report two cases of severe alloimmune hemolysis after hematopoietic stem cell (HSC) transplant resulting from an anti-Jk a . The time course of hemolysis and Jk phenotypes of the donor and recipient in the cases reported suggest that the antibody was produced by donor-derived passenger lymphocytes. Retrospective analysis of the blood bank records of all allogeneic HSC transplant patients at Barnes-Jewish Hospital from 1994 to 1999 suggests that the incidence of alloimmune hemolysis due to incompatibilities involving non-ABO or RhD red cell antigens is very low, approximately 1%. In one patient, the duration of hemolysis was shortened significantly by performing red cell exchange at the first sign of intravascular hemolysis. Bone Marrow Transplantation (2001) 27, 1305-1310. Keywords: allotransplantation; hemolysis; alloantibodies; stem cells Delayed immune hemolysis is an uncommon, but serious complication of HSC transplantation. Pretransplant clinical consideration is usually given only to ABO and Rh compatibility between the donor and recipient. [1][2][3][4] The occurrence of immune hemolyis in HSC transplant recipients who receive ABO or RhD-mismatched marrow has been estimated to be approximately 10% to 15%. 3 For example, in cases of major ABO mismatch, care is taken to red cell deplete the stem cell product prior to transplant. In the absence of pre-existing alloantibodies to non-ABO antigens in the donor or recipient, no further consideration is given prior to transplant to a potential non-ABO/RhD antigen mismatch.There are only a handful of reports in the literature reporting occurrences of non-ABO alloimmunization after allogeneic transplantation and only a few of these cases occurred following transplantation of HSCs derived either from bone marrow (BM) or peripheral blood mononuclear cells (PBMC) isolated by apheresis. 5-9 These reports suggest that, in contrast to patients with posttransplant hemolysis due to mismatches in the ABO system in whom hemolysis is usually moderate, non-ABO alloimmune hemolysis in the post HSC transplant setting was associated with episodes of severe hemolytic anemia presenting difficult clinical management issues. 8 No estimates of the frequency of non-ABO/RhD red cell alloimmunization in the post-transplant setting are available in the published literature.We present two case reports of severe immune hemolytic anemia after allogeneic HSC transplant resulting from donor-derived anti-Jk a . We also retrospectively reviewed the blood bank records of all patients at Barnes-Jewish Hospital who underwent allogeneic HSC transplantation (either BM or PBMC) between January 1994 and December 1999 to determine the incidence of non-ABO alloantibodymediated hemolysis in this population. Case 1The first patient was a 37-year-old white male with Philadelphia chromosome positive chronic myelogenous leukemia who presented with a WBC of 31 000. He was managed with hydroxyurea with adequate control for 2 years. Upon progression, a decision was made to proceed with a 6/6 HLA-matche...

Non-ABO red blood cell alloantibodies following allogeneic hematopoietic stem cell transplantation

“…Although immune hemolysis due to ABO or RhDmismatched marrow transplants is the most frequent immunohematological post-BMT complication, occurring in approximately 10-15% of such transplants, 6 other RBC antigen systems have been implicated less frequently in alloimmunization after allogeneic transplantation. [25][26][27][28][29][30] However, the medical literature reports many cases of hemolysis after BMT caused by alloantibodies directed against the Kidd, MNSs and Kell antigen systems.…”

“…15 Passenger lymphocyte syndrome 7 and chronic hemolysis (in the case of persistence of mixed chimerism) 8 have also been described Kell system Anti-Kell Delayed hemolytic anemia 25,28 Kidd system Anti-JK a , -JK b Severe acute hemolytic anemia with intravascular hemolysis (passenger lymphocyte syndrome), 6,29 delayed hemolytic anemia 25 …”

“…[3][4][5][6][7] Ting et al 3 described the production of non-ABO red cell alloantibodies in 13 of 150 patients (8.7%) after BMT. However, examining the series carefully, only nine of the 150 (6%) had non-ABO alloantibodies that had developed during the post-BMT period.…”

“…[25][26][27][28][29][30] However, the medical literature reports many cases of hemolysis after BMT caused by alloantibodies directed against the Kidd, MNSs and Kell antigen systems. 6,25,[28][29][30] The hemolysis may be severe if several alloantibodies are simultaneously involved. 25 We have previously described 28 an episode of mild hemolytic anemia 1 month after BMT due to a major Kell incompatibility (recipient with antiKell alloantibodies, donor Kell negative).…”

Minor RBC Ab and allo-SCT

“…In some cases, the Abs are believed to be due to passenger lymphocytes adoptively transferred during the stem cell infusion. 2 In other cases, it is believed that the Abs are produced by recipient B-cells that persist after myeloablation. A third possibility is a primary immune response to minor Ag-mismatched RBCs that were transfused in the posttransplant period.…”