Major ABO-incompatible Bone Marrow Transplantation Research Articles

Transfusion-related problems following major ABO-incompatible bone marrow transplantation

A case of acute myelocytic leukemia has been reported in which the patient’s surviving original B lymphocytes after pretransplant-conditioning chemotherapy probably reproduced hemagglutinins that reacted with red blood cells (RBCs) derived from engrafted donor marrow for a prolonged period of time. Although the direct antiglobulin test was negative and hemagglutinins were not detectable in the patient’s sera but only in the eluate, the antibodies reappeared in the sera. Therefore, it is important to confirm that the eluate does not contain antibodies that would react with donor-derived RBCs when the type of red cell used for transfusion is switched from the patient’s type to the donor’s type in a major ABO-mismatched bone marrow transplantation (BMT). Testing of ABO subgroups using lectins is also recommended to avoid a delayed hemolytic transfusion reaction following BMT.

Donor lymphocyte infusion as therapy for pure red cell aplasia following bone marrow transplantation

Pure red cell aplasia (PRCA) following allogeneic bone marrow transplantation (BMT) has been associated with major ABO incompatibility between donor and recipient red blood cells (3). Donor lymphocyte infusion (DLI) has been used with success following cytogenetic or haematologic relapse of chronic myeloid leukaemia (CML) after BMT (4). At our centre we initiated a study regarding the use of DLI as relapse prophylaxis in patients affected by acute lymphoblastic leukaemia (ALL) and submitted to BMT. We report the case of a patient with ALL who developed PRCA after ABO incompatible BMT and its unexpected successful treatment with DLI when other therapies failed. A 20-year-old female with ALL (L1, common) in first complete remission underwent an allogeneic BMT in October 1997. The donor was an HLA-compatible sister with blood group A+ and the recipient was O+. Busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) were used as conditioning therapy and 2.6 × 108/kg marrow cells were infused after removing red blood cells (RBC) by an automated cell separator (EXCEL-DIDECO, Mirandola, Italy). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine-A (CyA) and short-course methotrexate (MTX). On day 10 the patient developed acute GVHD grade I (skin), and was treated successfully with prednisone 2 mg/kg. Myeloid engraftment (ANC > 0.5 × 109/l) was observed on day 20 and platelets recovered (>25 × 109/l) on day 32. Reticulocyte counts were measured with Becton Dickinson FACScan flow cytometer and the absolute reticulocyte count was persistently <0.02 × 1012/l. Repeated examinations of bone marrow revealed complete absence of RBC precursors in an otherwise normal marrow. There was no evidence of haemolysis, blood loss or infections. The anti-A isoagglutinin titre was 1 : 8. A diagnosis of PRCA was made and recombinant human erythropoietin (rh-EPO) was started at a dose of 50 U/kg three times per week. From day 70, immunoglobulin, 400 mg/kg, was infused daily for 5 d, but anaemia persisted and the patient required regular RBC transfusions. A total of five plasmapheresis was then performed from day 125 to day 135 and the anti-A isoagglutinins became undetectable. However, the patient remained reticulocytopenic and transfusion-dependent. On day 170, while still under rh-EPO therapy, the patient received the first infusion of donor lymphocytes at the dosage of 1 × 106/kg, according to the leukaemic relapse prophylaxis protocol in use at our centre. Within 8 d a marked increase of the absolute reticulocyte counts and Hb levels was observed, with an absolute reticulocyte count of 0.9 × 1012/l and an untransfused Hb concentration of 8.5 g/dl (Fig 1). Neither acute nor chronic GVHD was observed and full engraftment of myeloid and megakaryocyte series persisted. At this time the patient discontinued CyA. After 6 and 12 weeks, respectively, the patient received increased doses of donor lymphocytes, the reticulocyte counts and Hb levels returned to normal values, blood group converted to type A and no further treatment was necessary. At 12 months post transplant the patient is asymptomatic. . Response of reticulocyte counts after administration of erythropoietin (rhEPO), immunoglobulins (Ig), plasmapheresis (Pl-aph), and donor lymphocytes (DLI). In major ABO incompatible BMT the persistence of functional host-derived lymphocytes and plasma cells that have survived the BMT conditioning regimen can result in delayed erythroid engraftment and increased RBC transfusions. It has been reported that PRCA usually resolves spontaneously, coincidentally with the decrease of agglutinin titre to <1:16 (2), but this was not the case in our patient. In the post-transplant period anti-A isoagglutinin titre remained at 1 : 4 to 1 : 8 and no erythropoiesis was observed. Transfusion dependence remained unchanged even after depletive plasmapheresis, when the isoagglutinins became undetectable in the peripheral blood. The stimulatory effect of rh-EPO on bone marrow erythroid precursors was insufficient to counteract the possible cell-mediated suppression of erythropoiesis. Some patients have responded to immunosuppressive therapy such as anti-lymphocyte globulin (1) or prednisone (5). In our patient the donor's lymphocytes infused at 170 d from BMT proved to be effective immunosuppression and a consistent increment of reticulocyte count was observed after 8 d. Probably the donor lymphocytes served to reinforce the novel immunocompetent system in suppressing the host's residual lymphocytes responsible for the erythrocyte blockage. The donor lymphocytes overcame the immunomodulation of the graft derived immune system due to CyA, which leads to temporary but prolonged prevalence of host lymphoid cells. We think that donor's lymphocytes may be cautiously used in patients who have received BMT for leukaemia and develop PRCA when GVHD is absent, and myeloid and megakaryocyte engraftment is complete.

Pure red cell aplasia after major ABO-incompatible bone marrow transplantation: two case reports of treatment with recombinant human erythropoietin

Abstract A 34-year-old man with acute myelocytic leukemia (AML: MO) and a 32-year-old woman with AML: M2 developed pure red cell aplasia (PRCA) after receiving a major ABO-incompatible bone marrow transplant (BMT). The first patient responded to recombinant human erythropoietin (rhEPO) therapy, while the second did not. The second patient also received methylprednisolone (m-PSL) but developed reticulocytosis and hemolysis after the administration of m-PSL. Plasmapheresis was then performed and the patient promptly recovered from hemolysis and PRCA. We conclude that close attention must be paid when treating PRCA following major ABO-incompatible BMT with rhEPO and m-PSL, as there is always the potential for massive hemolysis.

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.

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

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.

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.

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.

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.