Successful Treatment of Pure Red Cell Aplasia after Major ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with Repeated Doses of the Single-Agent Rituximab: A Case Report.
Authors: Mota Karla O. , Macedo Maria Cristina , Silva Roberto 
Published: October 2019

Background: ABO incompatibility occurs in up to 20–40% of HLA matched allogeneic hematopoietic stem cell transplantation (HSCT). Pure red cell aplasia (PRCA) following ABO-incompatible allogeneic HSCT is a rare complication associated with interaction of recipient anti-A or anti-B isoagglutinins, produced by residual B cells, with donor erythrocytes precursors expressing A and/or B antigens. The best treatment approach for PRCA is not established. Plasma exchange and immunoadsorption are regarded as a first-line treatment strategies. Other therapeutic approaches include: erythropoietn (EPO), donor-derived leukocyte infusion (DLI), steroids or induction of graft versus host disease (GVHD) by immunosuppression withdraw. Moreover, recovery or erythropoiesis is often incomplete and may induce futher complications. Recent reports describe successful treatment of PRCA and others cytopenias after HSCT using Rituximab (Mabthera®; Roche; Switzerland). This drug is a chimeric IgG1 monoclonal antibody directed against the CD20 surface antigen expressed by most human B lymphocytes. Its exact mechanism of action is not known.

Case Report: We treat a 47-year-old woman with PRCA after a major ABO-mismatched (Donor A Rh-; Recipient O Rh-) allogeneic HSCT after a second remission of a acute myeloid leukemia. Allogeneic HSCT was performed in November 2005, from a HLA-matched older sister, using bone marrow graft (Mn cell dose 1,72x108/kg) following a myeloablative conditioning with busulfan (16mg/kg) and melfalan (140mg/m2). GVHD prophylaxis included cyclosporine A and methotrexate. Baseline anti-A isoagglutinin IgM titers of the paient before transplantation was 1:128 and after immunoadsorption with plasma A for 48 hours decreased to 1:32. One plasmapheresis session was performed to remove ABO antibodies from the patient and her anti-A IgM titer dropped to 1:4 before bone marrow infusion. We also removed red blood cells from the donor’s marrow product to prevent risk of hemolysis. After bone marrow transplantation, the patient developed a severe anemia that required weekly red blood cells transfusion over six months. Reticulocyte counts were extremely low during this period, bone marrow aspirate was normal, except for decreased erythrocyte precursors (only 1% of total cells). In August 2006, the diagnosis of PRCA was set after exclusion of red blood cells alloantibodies, hemolysis and viral or bacterial infection. Donor chimerism (STR) was totally completed and the recipient anti-A IgM titer was 1:16 and the patient showed no evidence of GVHD. In October 2006, she was treated with rituximab 375mg/m2 administered once weekly for four weeks. In the next two months, after the treatment with rituximab, her hemoglobin (Hb) increased from 5.5g/dl to 12g/dl. Up to her last medical avaluation (July 2006), she was in PRCA remission, her Hb was 12g/dl and she had no detectable anti-A titer. Conclusion: Rituximab can be a very effective treatment to PRCA secondary to major ABO-incompatible allogeneic stem cell transplantation. The best dose schedule and long term effects must be establish.