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Fludarabine- and Cyclophosphamide-Based Nonmyeloablative Conditioning Regimen for Transplantation of Chronic Granulomatous Disease: Possible Correlation with Prolonged Pure Red Cell Aplasia

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Abstract

An 18-year-old patient with chronic granulomatous disease who had had at least 2 episodes of life-threatening Aspergillus pneumonia was treated with nonmyeloablative allogeneic stem cell transplantation (NSCT) from an HLA-identical and major ABO-incompatible sibling. The conditioning regimen consisted of cyclophosphamide at a dose of 60 mg/kg (days -5, -4) and fludarabine at a dose of 30 mg/m2 (days -5, -4, -3, -2, -1). Full donor T-cell engraftment was attained on day 28, and full myeloid engraftment was established by day 150 after tacrolimus withdrawal.The bacteriocidal activity of neutrophils, as indicated by flow cytometry with the use of a dichlorofluorescein diacetate oxidation assay, remained low until 150 days after transplantation, but no infection was detected, a finding that suggests mixed chimerism of granulocytes controlled infection. Graftversus-host disease and severe regimen-related toxicity (grade 3 or greater) were not observed. This patient developed prolonged pure red cell aplasia, possibly caused by persistent antidonor isohemagglutinin produced by the residual host B-cells. The aplasia resolved with the combination of erythropoietin, double filtration plasmapheresis, and rituximab. In the setting of major ABO-incompatible NSCT, a fludarabine- and cyclophosphamide-based conditioning regimen may lead to prolonged PRCA.

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Authors and Affiliations

  1. Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, 980-8574, Sendai, Japan

    Tohru Fujiwara, Minami Yamada, Koichi Miyamura, Yasuo Tomiya, Kenichi Ishizawa, Junichi Kameoka & Takeshi Sasaki

  2. Molecular Diagnostics, Sendai, Japan

    Hideo Harigae

  3. Division of Blood Transfusion, Sendai, Japan

    Masayoshi Minegishi

  4. Department of Pediatric Oncology, Tohoku University School of Medicine, Sendai, Japan

    Shigeru Tsuchiya

Authors
  1. Tohru Fujiwara
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  2. Minami Yamada
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  3. Koichi Miyamura
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  4. Yasuo Tomiya
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  5. Kenichi Ishizawa
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  6. Hideo Harigae
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  7. Junichi Kameoka
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  8. Masayoshi Minegishi
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  9. Shigeru Tsuchiya
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  10. Takeshi Sasaki
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Corresponding author

Correspondence to Koichi Miyamura.

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Fujiwara, T., Yamada, M., Miyamura, K. et al. Fludarabine- and Cyclophosphamide-Based Nonmyeloablative Conditioning Regimen for Transplantation of Chronic Granulomatous Disease: Possible Correlation with Prolonged Pure Red Cell Aplasia. Int J Hematol 79, 293–297 (2004). https://doi.org/10.1532/IJH97.03123

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  • DOI: https://doi.org/10.1532/IJH97.03123

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