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Inherited and Genetic Disorders

Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia

Bone Marrow Transplantation volume 52, pages 570–573 (2017)Cite this article

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Abstract

We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA.

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Acknowledgements

We thank the children with FA and their families for allowing us to care for them and for participating in our clinical trial. We are indebted to Dr Leo Luznik for our conversations regarding the modification of the posttransplant CY dosing. We give many thanks to our Clinical Research Coordinators at each site for data collection, management and integrity. We also thank Ms Helen Crawford and Ms Bonnie Larson for their assistance in manuscript preparation. Support for this study was provided by the Fanconi Anemia Research Fund (FARF) and by grants from the National Heart, Lung and Blood Institute (NHLBI), NIH, (Bethesda, MD, USA), numbers HL036444 and HL122173. HPK is a Markey Molecular Medicine Investigator and received support as the inaugural recipient of the José Carreras/E.D. Thomas Endowed Chair for Cancer Research.

Author contributions

MT designed the trial, wrote the protocol, enrolled patients, analyzed the data and wrote and edited the manuscript. CB, MW and RP enrolled patients, analyzed data and edited the manuscript. RS designed the trial and edited the manuscript. BS designed the trial, analyzed the data, enrolled patients and edited the manuscript. LB analyzed the data and edited the manuscript. AW and H-PK designed the trial, analyzed the data and edited the manuscript.

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Authors and Affiliations

  1. Pediatric Hematology Oncology, Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    M S Thakar

  2. Hospital de Clinicas, Universidade do Parana, Curitiba, Brazil

    C Bonfim & R Pasquini

  3. UCSF Benioff Children’s Hospital Oakland, Oakland, CA, USA

    M C Walters

  4. Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA

    R Storb, L Burroughs, B M Sandmaier, A Woolfrey & H-P Kiem

  5. Seattle Children’s Hospital, Seattle, WA, USA

    L Burroughs & A Woolfrey

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  1. M S Thakar
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  2. C Bonfim
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  4. R Storb
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Correspondence to M S Thakar.

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Thakar, M., Bonfim, C., Walters, M. et al. Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia. Bone Marrow Transplant 52, 570–573 (2017). https://doi.org/10.1038/bmt.2016.301

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