Transmission of an anti-RhD alloantibody from donor to recipient after ABO-incompatible BMT

Abstract

Summary:We report a bone marrow transplant which was HLA matched, with major and minor ABO and minor RhD incompatibility (anti-RhD antibody) between the donor and recipient. When engraftment occurred, the recipient developed an anti-RhD antibody of donor origin detected by direct and indirect antiglobulin tests (DAT, IAT) and showed signs of mild hemolytic anemia. With the disappearance of the recipient RBCs, the DAT became negative and the hemolysis disappeared, while the anti-RhD alloantibody persisted in the patient's serum. This case emphasizes the importance of close immuno-hematological monitoring in patients undergoing allogeneic BMT with ABO-RhD incompatibility between recipient and donor. Keywords: bone marrow transplantation; ABO-RhD incompatibility; alloantibody; hemolytic anemia A 50-year-old male patient, affected by AML (FAB M5), was referred to us for a BMT from his HLA-identical sister, during his first complete remission after chemotherapy. His pre-transplant RBC phenotype was B CcDee (anti-A titer: IgM 256, IgG 128). Antibody screening (indirect antiglobulin test (IAT) ) and direct antiglobulin test (DAT) were negative. The bone marrow donor was a 40-year-old female, whose RBC phenotype was A ccdee (anti-B titer: IgM 512, IgG 64). The IAT showed the presence of an anti-RhD alloantibody, titer 2. This woman had had no pregnancies and had received blood transfusions a few years previously because of a severe anemia due to a uterine hemorrhage.The patient underwent conditioning therapy in July 1996 with hyperfractioned TBI and high-dosage CY. He subsequently received his sister's bone marrow: 1380 ml of marrow were collected from the donor's iliac crests. Due to the major and minor ABO incompatibility, the plasma was removed from the harvested bone marrow by spinning at 4000 r.p.m. × 10 min, and then the bone marrow was isovolumetrically re-suspended in saline 0.9% and the RBC were removed by sedimentation in 12.5% hydroxyethyl starch. A 636 ml suspension of bone marrow cells with a few red cells (equivalent to 15 ml of whole blood with 40% hematocrit) was obtained. The bone marrow was re-infused into the recipient through a central venous catheter, at a rate of 160 ml/h (infusion time: 4 h). During the aplasic period the patient received 9 units of group O Rh-negative RBC, 12 units of single donor platelets (group AB) and 24 units of random pool platelets (group O), that had been re-suspended in 0.9% saline after the plasma had been removed. All blood products were irradiated to 24 Gy and filtered (RXCL 1 PALL filters for RBC and PL 100 PALL filters for platelets). On day 24, the platelets were Ͼ20 × 10 9 /l and the granulocytes Ͼ0.5 × 10 9 /l; a bone marrrow smear confirmed engraftment. The DAT was weakly positive (IgG+, C3dϪ), while the IAT remained negative; an eluate was inconclusive. RBC ABO grouping test showed the presence of RBC from two different blood groups: group O from RBC transfusions and group B from the recipient. Serum ABO grouping was only positive with A 1 RBC. The anti-A 1 (Ig...

Red blood cell-incompatible allogeneic hematopoietic progenitor cell transplantation

“…However, non-ABO antigen systems have been implicated in post-transplant reactions and red cell incompatibility encompasses ABO, rhesus (Rh) and other red cell antigen systems. 5,6 Definition of RBC-incompatible transplants Red cell incompatibility may be classified into two major categories, one in which the recipient has antibodies directed against donor red cells with the potential of acute hemolytic transfusion reaction upon infusion of the stem cell product and delayed recovery of red cell function after transplantation (major incompatibility), and one in which the donor has antibodies against the recipient (minor incompatibility). Although the latter may rarely cause difficulty from infusion of incompatible plasma with high isoagglutinin titers, B-lymphocytes carried in the component ('passenger lymphocytes') can produce isoagglutinins resulting in a delayed transfusion reaction usually 7-12 days after transplantation.…”

Hematopoietic stem cell transplantation between red cell incompatible donor–recipient pairs

“…However, red cell antigens of other systems can also present a challenge for management of the transplant patient if antibodies exist either in the donor or recipient and red cell incompatibility encompasses ABO, Rh, and other red cell antigen systems. 4,5 Basic immunohematology principles apply to the infusion of red cell incompatible HSC components -processing of the component or preparation of the recipient may be necessary to prevent hemolysis of donor or recipient red blood cells as a result of the infusion of incompatible red blood cells or plasma contained within the HSC component. [2][3][4][5][6][7][8] This, of course, applies only to those antigen systems capable of causing hemolytic transfusion reactions at body temperature.…”

“…4,5 Basic immunohematology principles apply to the infusion of red cell incompatible HSC components -processing of the component or preparation of the recipient may be necessary to prevent hemolysis of donor or recipient red blood cells as a result of the infusion of incompatible red blood cells or plasma contained within the HSC component. [2][3][4][5][6][7][8] This, of course, applies only to those antigen systems capable of causing hemolytic transfusion reactions at body temperature. However, in contrast to blood transfusion, the risk of hemolysis occurs not only at the time of infusion but can also can occur later if viable lymphocytes in the HSC component produce isoagglutinins directed against recipient red cell antigens.…”

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

“…Rh system Anti-D, -C, -c, -E Delayed hemolytic anemia, 13,21,32 which may be severe after major Rh-mismatched grafts. 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 …”

“…Although bone marrow transplants with Rh incompatibility involving C, c and E antigens have been described in the medical literature, 7,10,11 most reports regard the D antigen. [12][13][14][15][16] Like ABO incompatibility, RhD incompatibility can cause hemolytic anemia after BMT. 9 A major RhD incompatibility between donor and recipient of a BMT may lead to a severe delayed hemolytic anemia.…”