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Inherited and Genetic Disorders

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

Bone Marrow Transplantation volume 49, pages 913–920 (2014)Cite this article

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Abstract

BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8–16 mg/kg, fludarabine 180 mg/m2, alemtuzumab 54 mg/m2 (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3–20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II–IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.

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Acknowledgements

The authors would like to thank all the families who participated in this clinical trial and all the faculty and staff on the Pediatric Blood and Marrow Transplant unit at Columbia University. This research was supported in part by grants from the Pediatric Cancer Research Foundation (MSC), Doris Duke Charitable Foundation (MG and KR) and Food and Drug Administration (5R01FD004090-02) (MSC).

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Authors and Affiliations

  1. Department of Pediatrics, Columbia University, NewYork-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA,

    M Bhatia, Z Jin, C Baker, K Radhakrishnan, P Satwani, D George, J Garvin, W Zuckerman, M T Lee, M Licursi, R Hawks & E Smilow

  2. Department of Biostatistics, Columbia University, NewYork-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA,

    Z Jin

  3. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA,

    M B Geyer

  4. Department of Pediatrics, New York Medical College, Valhalla, NY, USA,

    E Morris & M S Cairo

  5. Department of Pediatrics, Wyckoff Heights Medical Center, New York, NY, USA,

    G Del Toro

  6. Department of Surgery, University of California San Francisco, San Francisco, CA, USA,

    L A Baxter-Lowe

  7. Department of Pathology, Columbia University, NewYork-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA,

    J Schwartz

  8. Department of Medicine, New York Medical College, Valhalla, NY, USA,

    M S Cairo

  9. Department of Pathology, New York Medical College, Valhalla, NY, USA,

    M S Cairo

  10. Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA,

    M S Cairo

  11. Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    M S Cairo

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  1. M Bhatia
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Correspondence to M Bhatia.

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Bhatia, M., Jin, Z., Baker, C. et al. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant 49, 913–920 (2014). https://doi.org/10.1038/bmt.2014.84

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