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Cold agglutinin disease associated with adenovirus infection after allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 36, pages 263–264 (2005)Cite this article

Autoimmune hemolytic anemia is an infrequent complication following allogeneic hematopoietic stem cell transplantation.1, 2, 3 Among the types of autoimmune hemolytic anemia, cold agglutinin disease (CAD) due to a cold-reactive antibody is rarely reported.1, 2, 3, 4 We describe here a case of CAD due to a cold-reactive anti-Pr antibody, which occurred simultaneously at the onset of adenovirus hemorrhagic cystitis after allogeneic bone marrow transplantation (BMT).

A 39-year-old female with myelodysplastic syndrome (refractory anemia) underwent allogeneic BMT from her one human leukocyte antigen (HLA) mismatched, ABO-matched sister. She was conditioned with total body irradiation (120 cGy) and cyclophosphamide (120 mg/kg), and received tacrolimus and short-term methotrexate as a prophylaxis for graft-versus-host disease (GVHD). She did not receive antithymocyte globulin, and bone marrow graft was not T-cell depleted. Her post-transplant course was not remarkable except for extensive-type chronic GVHD of the mouth, skin, and gastrointestinal tracts, diagnosed around day 160. Chronic GVHD responded well to systemic administration of corticosteroid and cyclosporine A (CSA). On day 240, when she was still on CSA and receiving tapering doses of corticosteroid without active chronic GVHD, she developed macroscopic hematuria accompanied by urinary urgency. Adenovirus (type 11) was detected in her urine by conventional qualitative polymerase chain reaction and shell vial assay. Detection of adenovirus in the urine and the urinary symptoms led to the diagnosis of adenovirus hemorrhagic cystitis. At the onset of hemorrhagic cystitis, the blood tests showed a rapidly progressing anemia (hemoglobin level decreased from 10.1 to 5.2 g/dL over 6 days) with marked reticulocytosis (13.1%). Her serum level of lactate dehydrogenase was 651 IU/l (normal range; 120–210 IU/l). Cold agglutinin was detected at the titer of 1:256 in the serum. Her direct antiglobulin test was strongly positive, attributable to complement (C3d); the indirect antiglobulin test also detected a free antibody in the serum. Agglutination titers of the antibody were measured at 4, 20, 30, and 37°C, and the antibody was found to have thermal amplitude up to 30°C. The antibody reacted with adult, cord, and adult i-positive red blood cells, but failed to react with papain-treated and sialidase-treated red blood cells. These findings strongly suggested that the antibody had the characteristics of an anti-Pr antibody.5, 6 The patient was treated with a transfusion of warmed red blood cell products, and an increased dose of corticosteroid (1 mg/kg) in addition to avoiding cold exposure. No transfusion-associated reactions were observed. During this period, hemorrhagic cystitis completely improved in a month. Corticosteroid was tapered after a 2-week administration, and cold agglutinin was no longer detected in the patient's serum 3 months after the onset of hemolysis.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology, Keio University School of Medicine, Tokyo, Japan

    T Mori, Y Yamada, Y Aisa, Y Ikeda & S Okamoto

  2. Department of Transfusion Medicine and Cell Therapy, Keio University Hospital, Tokyo, Japan

    T Uemura & A Ishida

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  1. T Mori
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  2. Y Yamada
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  3. Y Aisa
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  7. S Okamoto
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Mori, T., Yamada, Y., Aisa, Y. et al. Cold agglutinin disease associated with adenovirus infection after allogeneic bone marrow transplantation. Bone Marrow Transplant 36, 263–264 (2005). https://doi.org/10.1038/sj.bmt.1705029

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