Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41-year-old man with chronic myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA-identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous-flow blood cell separator. The patient was given group O Rh-positive RBCs and group A Rh-positive platelets. Prophylaxis for graft-versus-host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti-M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti-K. During the second hemolytic episode (Day 35), the patient's blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the serum. Eluates made from the recipient's RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum and in an eluate made from the patient's RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.