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Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only

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Abstract

Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II–IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.

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Acknowledgments

We thank all the referring centers for entrusting their patients to our care. MMC is supported by the Deutsche Kinderkrebsstiftung. For the analyses of clonal chromosome aberrations, HN received grants from the Deutsche Fanconi Anämie Hilfe e.V. and the Fanconi Anemia Research Fund. The GEFA Registry is supported by the Deutsche Fanconi Anämie Hilfe e.V.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatric Hematology Oncology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany

    M. M. Chao, M. Zimmermann & C. P. Kratz

  2. Department of Pediatric Oncology, Hematology, and Stem Cell Transplantation, Charité University Medicine Berlin, Berlin, Germany

    J. S. Kuehl, G. Strauss & W. Ebell

  3. Department of Pediatrics and Human and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

    H. Hanenberg

  4. Department of Otorhinolaryngology, Head and Neck Surgery, Heinrich Heine University, Düsseldorf, Germany

    H. Hanenberg

  5. Department of Human Genetics, University of Wuerzberg, Wuerzberg, Germany

    D. Schindler

  6. Institute of Medical and Human Genetics, Charité University Medicine Berlin, Berlin, Germany

    H. Neitzel

  7. Department of Pediatric Hematology Oncology, Freiburg University School of Medicine, Freiburg, Germany

    C. Niemeyer

  8. Department of Pathology, Boeblingen Hospital, Clinical Centre South West, Boeblingen, Germany

    I. Baumann

  9. Department of Pediatric Pulmonology and Immunology, Charité University Medicine Berlin, Berlin, Germany

    H. von Bernuth

  10. Department of Immunology, Laboratory Berlin Charité Vivantes GmbH, Berlin, Germany

    H. von Bernuth

  11. Institute of Legal and Forensic Medicine, Charité University Medicine Berlin, Berlin, Germany

    J. Rascon & M. Nagy

  12. Center for Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania

    J. Rascon

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  1. M. M. Chao
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  2. J. S. Kuehl
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Correspondence to M. M. Chao.

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Chao, M.M., Kuehl, J.S., Strauss, G. et al. Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only. Ann Hematol 94, 1311–1318 (2015). https://doi.org/10.1007/s00277-015-2370-7

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  • DOI: https://doi.org/10.1007/s00277-015-2370-7

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