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Allografting

Targeted Busulfan therapy with a steady-state concentration of 600–700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant

Bone Marrow Transplantation volume 49, pages 366–369 (2014)Cite this article

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Abstract

Busulfan (BU) has a narrow therapeutic window and the average concentration of BU at steady state (Css) is critical for successful engraftment in children receiving BU as part of the preparative regimen for allogeneic transplants. Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow transplant (BMT) from HLA-identical siblings. The preparative regimen consisted of intravenous BU 0.8–1 mg/kg/dose for 16 doses, cytoxan (CY) of 50 mg/kg daily for four doses and equine anti-thymocyte globulin (ATG) 30 mg/kg daily for three doses. BU levels were adjusted to provide a total exposure Css of 600–700 ng/mL. The median age at the time of transplant was 6.2 years (range 1.2–19.3). Fourteen (87%) patients required adjustment of the BU dose to achieve a median Css of 652 ng/mL (range 607–700). All patients achieved neutrophil and platelet engraftment without significant toxicity. Median donor engraftment at the last follow-up was 100% (range 80–100). None of the patients experienced sickle cell-related complications post transplant. With a median follow-up of 3 years (range 1.3–9), the event-free survival (EFS) and overall survival (OS) are both 100%. We conclude that targeting of BU Css between 600 and 700 ng/mL in this regimen can result in excellent and sustained engraftment in young patients with SCD.

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Acknowledgements

We would like to thank Alisha McCord and Ryan Frangoul for the administrative support. This project was supported by the Carolyn Perot Rathjen Chair in Pediatrics, Nashville, TN, USA (Haydar Frangoul, MD).

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Author notes

  1. H Frangoul and E Yang: Haydar Frangoul and Elizabeth Yang share senior authorship.

Authors and Affiliations

  1. Department of Pediatrics, Inova Children’s Hospital, Falls Church, VA, USA

    S Maheshwari

  2. Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    A Kassim

  3. Pharmacokinetics Laboratory, Seattle Cancer Care Alliance, Seattle, WA, USA

    R F Yeh

  4. Division of Hematology/Oncology, Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA

    J Domm, C Calder, M Evans, B Manes, V Brown, R Ho & H Frangoul

  5. Department of Pharmacy, Vanderbilt University, Nashville, TN, USA

    K Bruce

  6. Department of Hematology and Oncology, Children’s National Medical Center, Center for Cancer and Blood Disorders of Northern Virginia, Falls Church, VA, USA

    E Yang

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  1. S Maheshwari
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Correspondence to H Frangoul.

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Maheshwari, S., Kassim, A., Yeh, R. et al. Targeted Busulfan therapy with a steady-state concentration of 600–700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant. Bone Marrow Transplant 49, 366–369 (2014). https://doi.org/10.1038/bmt.2013.188

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  • DOI: https://doi.org/10.1038/bmt.2013.188

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