ABO-incompatible Bone Marrow Transplantation Research Articles

Treatment with Bolus Methylprednisolone for Pure Red Cell Aplasia after ABO Incompatible Bone Marrow Transplantation in a Patient with Chronic Myelocytic Leukemia

Treatment with Bolus Methylprednisolone for Pure Red Cell Aplasia after ABO Incompatible Bone Marrow Transplantation in a Patient with Chronic Myelocytic Leukemia

Erythropoietin in the treatment of delayed immune hemolysis of a major ABO‐incompatible bone marrow transplant

Delayed immune hemolysis can be observed after major ABO-incompatible bone marrow transplants (BMT). The management of these hemolytic episodes includes transfusion of group O red blood cells and increases of immunosuppression. Here we report the case of a 25-year-old patient who developed overt immune hemolysis on day +50 after a HLA-identical ABO-incompatible BMT. To avoid added immunosuppression, erythropoietin was started: an increase in reticulocytes sufficient to maintain hemoglobin despite persistent hemolysis was observed. We conclude that erythropoietin may have a role in the management of delayed-onset hemolysis of major ABO-incompatible BMT, especially when added immunosuppression is undesirable.

A simple technique for red blood cell removal in major ABO-incompatible bone marrow transplantation.

A simple technique for red blood cell (RBC) removal in major ABO-incompatible bone marrow transplantation is reported requiring two centrifugation steps, special blood bags and a mechanical device to separate the buffy coat from RBCs within the bag. In 42 transplantations an average of 84% of nucleated cells was recovered with an average contamination of 7.5 ml packed RBCs. The preparations were well tolerated in all patients whose isoagglutinin titers had not been reduced. Bone marrow engraftment was not significantly different from control groups.

A Simple Technique for Red Blood Cell Removal in Major ABO-Incompatible Bone Marrow Transplantation

A simple technique for red blood cell (RBC) removal in major ABO-in- compatible bone marrow transplantation is reported requiring two centrifugation steps, special blood bags and a mechanical device to separate the buffy coat from RBCs within the bag. In 42 transplantations an average of 84% of nucleated cells was recovered with an average contamination of 7.5 ml packed RBCs. The preparations were well tolerated in all patients whose isoagglutinin titers had not been reduced. Bone marrow engraftment was not significantly different from control groups.

Successful Treatment of Prolonged Anemia after Major ABO Incompatible Bone Marrow Transplantation for a Case of Myelodysplastic Syndrome with Recombinant Erythropoietin

Successful Treatment of Prolonged Anemia after Major ABO Incompatible Bone Marrow Transplantation for a Case of Myelodysplastic Syndrome with Recombinant Erythropoietin

Bone marrow processing with the Fresenius AS 104: initial results.

Prior to purging, cryopreservation, or ABO-incompatible bone marrow (BM) transplantation, we have concentrated 23 BM harvests using a modification of the "grancollect-protocol" and the recently available bone marrow stem cell (BMSC) protocol of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 minutes, the initial marrow volume of 922 ml (+/- 408 ml) was processed two to three times. A mean of 59% (+/- 20%) of the initial mononuclear cells was recovered in a mean volume of 119 ml (+/- 31 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 98% (+/- 80%). Red blood cells in the BM concentrates were reduced to 8% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation, and transplantation. All transplanted patients showed fast and sustained engraftments after autologous or allogeneic BM transplantation.

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with recombinant erythropoietin [letter; comment

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with recombinant erythropoietin [letter; comment

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with recombinant erythropoietin [letter; comment

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with recombinant erythropoietin [letter; comment

Delay in Red Blood Cell Recovery after Major ABO Incompatible Bone Marrow Transplantation

Delay in Red Blood Cell Recovery after Major ABO Incompatible Bone Marrow Transplantation

Monoclonal Antibody to Blood Group Glycosyltransferases, Produced by Hybrids Constructed with Epstein‐Barr‐Virus‐Transformed B Lymphocytes from a Patient with ABO‐Incompatible Bone Marrow Transplant and Mouse Myeloma Cells

A patient with chronic myeloid leukemia secreted an antibody to blood group glycosyltransferases after ABO-incompatible bone marrow transplantation (B recipient/O donor). Peripheral B lymphocytes from the recipient were transformed with Epstein-Barr virus, and then fused by polyethylene glycol with mouse myeloma cell line P3-X63/Ag8.653. After the cloning of the hybridoma cells, a cell line which produced human IgM antibody to blood group glycosyltransferases was established. The antibody completely neutralized B transferase activity at low concentration, while a larger amount of immunoglobulins was required to neutralize A transferase activity.

Monoclonal Antibody to Blood Group Glycosyltransferases, Produced by Hybrids Constructed with Epstein-Barr-Virus-Transformed B Lymphocytes from a Patient with ABO-Incompatible Bone Marrow Transplant and Mouse Myeloma Cells

A patient with chronic myeloid leukemia secreted an antibody to blood group glycosyltransferases after ABO-incompatible bone marrow transplantation (B recipient/O donor). Peripheral B lymphocytes from the recipient were transformed with Epstein-Barr virus, and then fused by polyethylene glycol with mouse myeloma cell line P3-X63/Ag8.653. After the cloning of the hybridoma cells, a cell line which produced human IgM antibody to blood group glycosyltransferases was established. The antibody completely neutralized B transferase activity at low concentration, while a larger amount of immunoglobulins was required to neutralize A transferase activity.

Administration of Haptoglobin in ABO Incompatible Bone Marrow Transplantation

Administration of Haptoglobin in ABO Incompatible Bone Marrow Transplantation

Pure Red Cell Aplasia of Long Duration Complicating Major ABO-Incompatible Bone Marrow Transplantation

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.

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

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.

Pure Red-Cell Aplasia of Long Duration after Major ABO-Incompatible Bone Marrow Transplantation

We describe a patient with an exceptionally long-lasting red-cell aplasia of 330 days following ABO-incompatible bone marrow transplantation (BMT). Before BMT, the anti-B titre was high, 1:1,024, and it was only temporarily reduced by extensive plasma exchange. The anti-B titre remained above the level of 1:64 for 270 days, and host-derived isoagglutinin could still be detected 3 years after BMT. In vitro bone marrow cultures during the red-cell aplasia showed greatly reduced numbers or total absence of CFU-E, while the number of BFU-E colonies was only moderately subnormal. Six years after BMT, bone marrow and peripheral-blood cell counts are normal.

Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO‐mismatched allogeneic bone marrow transplant recipient

ABO-mismatched bone marrow transplants have resulted in delayed red cell production in patients who have persistently elevated anti-ABO isohemagglutinin titers. We present a patient with chronic myelogenous leukemia who received an HLA-matched, ABO-incompatible bone marrow transplant from his sister. Post-transplant, he developed pure red cell aplasia with exuberant production of donor red cell precursors by in vitro BFU-E assay. Restriction fragment length polymorphism (RFLP) analysis of bone marrow, peripheral blood and BFU-E colonies demonstrated only donor type DNA post-transplant. However, the patient had persistently elevated isohemagglutinin titer and Ph1 chromosome-positive metaphases on chromosome analysis, indicating the presence of persistent host lymphocytes. With onset of acute graft vs. host disease (GVHD), the isohemagglutinin titer dropped, Ph1 chromosome-positive metaphases disappeared, and full hematopoietic recovery ensued. Longitudinal analysis of RFLP's, isohemagglutinin titers and chromosomes may be helpful in understanding the immunological interplay following allogeneic bone marrow transplantation.

ABO-incompatible bone marrow transplantation: Three methods for the removal of red blood cell antibodies

We analyzed three different methods for removing red blood cell (RBC) antibodies in 28 patients before a major ABO-incompatible bone marrow transplantation (BMT). Six patients were treated with extensive plasma exchange. Antibody titers were lowered from 1:512 to 1:4 (median values). In ten patients antibodies were removed by extracorporeal immunoadsorption using an adsorbent column. Titers decreased from 1:128 to 1:32. In four of these ten patients plasma exchange was added to complete antibody removal. Twelve patients were treated with simple in vivo adsorption with donor-type RBCs before marrow infusion. In eight of them, titers became undetectable. Advantages and disadvantages of the three methods are discussed.

Immunoadsorption for removal of anti-A and anti-B blood group antibodies in ABO-incompatible bone marrow transplantation.

About 10-15 percent of all patients undergoing allogeneic bone marrow transplantation have a major ABO-incompatibility with their donors. The risk of acute hemolytic reactions due to the infusion of an incompatible donor marrow into the recipient can basically be prevented by recipient antibody depletion or by donor marrow red cell depletion. Nine patients were treated by immunoadsorption using a cartridge with chemically synthesized human blood group A and B antigen as immunoadsorbent for antibody depletion. Within a four-hour-procedure about 2-4 times the patient plasma volume could be processed, thus lowering the anti-A and -B hemagglutinins by 2 to 3 tubes. There was a tendency of better IgG removal when titers initially were high, showing a high antibody clearing capacity. There was no significant correlation between starting titer or amount of plasma volume processed and titer reduction. No decrease in titers were observed in one case. We propose repeated immunoadsorption procedures over 2-3 consecutive days before BMT. The procedure is largely safe and without serious side effects. A major advantage is the avoidance of nonautologous human blood products compared to the conventional plasma exchange. All 8 patients surviving long enough had prompt and stable engraftment of all three cell lines post BMT. No late serological complications occurred when patients were regularly monitored and in vivo adsorption was used when titers increased.

A bone marrow transplant with an acquired anti-Le a: A case study

A patient with aplastic anemia received an ABO incompatible bone marrow transplant (BMT) from an HLA identical sibling. Weekly HLA antibody screens were performed as part of the BMT protocol. At the time of transplant, a hemolytic anti-Le a was detected in the Le (a−b−) donor. The le (a−b+) recipient had no red cell or LCT antibody. A hemolytic anti-Le a was detected in the recipient on day 8, but no LCT reactivity was noted at this time. On day 15, the LCT panel demonstrated reactivity with 9 of 50 panel cells without apparent HLA specificity. Graft vs. host disease (GVHD) was present on the skin at this time. The dose of cyclosporin A was increased, but by day 20 the GVHD worsend and the LCT titers increased to 8. This strong reactivity was noted only in the Le (a+) panel members (12/50) and was neutralized with commercial Lewis substance. On day 34 there was no evidence of GVHD, but the lymphocytotoxic anti-Le a continued to be present. The patient began experiencing renal and gastrointestinal difficulties by day 48, and expired on day 60. In renal transplants the kidneys retain their Lewis type and secrete Lewis substance in the urine. In our experience BMT patients retain their Lewis type regardless of the type of the donor. The Lewis system has been linked to renal allograft rejection, and Lewis antigens may function as transplantation antigens in BMT patients as well. In addition, lymphocytotoxic Lewis antibodies can mask other significant HLA antibodies and must be identified when screening patients in need of plateletpheresis products.

Transplantation of Major ABO‐Incompatible Bone Marrow Depleted of Red Cells by Hydroxyethyl Starch1

23 bone marrow transplant recipients whose donors where major ABO-incompatible received marrow depleted of red cells prior to infusion utilizing gravity sedimentation in hydroxyethyl starch. The in vitro red cell-depletion procedure effectively removed 97.8% (mean) of the red cells from the harvested marrows and preserved 86.8% of the nucleated cells and 98.2% of the CFU-C activity in 25.4% of the original volume. All recipients had a significant quantity of isohemagglutinins of both IgM and IgG classes demonstrable in their serum at the time of the marrow infusion. Patients were premedicated and well-hydrated prior to the infusion and tolerated the infusion well. These patients demonstrated bone marrow engraftment at the same rate as did those patients whose marrow donors were either ABO-identical or minor ABO-incompatible. There was no difference in the incidence of or time to development of graft versus host disease, the incidence of graft rejection, or patient survival among the groups. Recipients of red cell-depleted major ABO-incompatible bone marrow transplants demonstrated production of donor-type red cells somewhat later and required slightly more red cell transfusion support that did the other groups of recipients. This red cell-depletion technique is safe and effective in the management of major ABO-incompatible bone marrow transplantation.