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Veno-occlusive disease after high-dose busulfan–melphalan in neuroblastoma

Bone Marrow Transplantation volume 55, pages 531–537 (2020)Cite this article

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Abstract

Survival for high-risk neuroblastoma patients is still suboptimal. Although stem cell transplantation (SCT) is used, there is no consensus as to which conditioning regimen has the greatest efficacy and fewest toxicities. We assessed the incidence of and risk for hepatic veno-occlusive disease (VOD) for neuroblastoma patients who underwent autologous SCT with busulfan and melphalan (BuMel) at eight centers following Children’s Oncology Group (COG)-based induction chemotherapy. Data regarding the patients, SCT characteristics, busulfan steady-state concentrations, incidence of VOD, and survival were evaluated. VOD was defined using the modified Seattle criteria. Possible factors associated with VOD (age, busulfan-pharmacokinetic parameters, history of hepatic dysfunction, and day of neutrophil engraftment) were evaluated. Seventy five patients were included and 23 children (31%) developed VOD at a median of 19 days after SCT (range 14–27 days). VOD was the cause of death in 4 patients (5%). In a multivariable analysis, young age (OR 1.7 (95% CI: 1.16–2.56; p = 0.012)) and early day of neutrophil engraftment (OR 1.4 (95% CI: 1.08–2.14; p = 0.041) were associated with the development of VOD. Initial or cumulative busulfan steady-state concentration were not associated with VOD. We found that despite the use of intravenous busulfan with adjusted serum levels, the incidence of VOD remains high in pediatric neuroblastoma patients.

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Author notes

  1. These authors contributed equally: Tal Schechter, Evelio Perez-Albuerne

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Tal Schechter & Meredith S. Irwin

  2. Division of Stem-Cell Transplant, Children’s National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Evelio Perez-Albuerne & David Jacobsohn

  3. Department of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, USA

    Tiffany F. Lin & Christopher C. Dvorak

  4. Department of Pediatric Haematology/Oncology, King Abdullah Specialized Children’s Hospital, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard, Riyadh, Saudi Arabia

    Mohammed Essa

  5. Department of Pediatrics, Section of Hematology/Oncology & Stem Cell Transplantation, The University of Chicago, Chicago, IL, USA

    Ami V. Desai

  6. Pediatric Stem Cell Transplant Program The Children’s Hospital, TriStar Centennial and Sarah Cannon Research Institute, Nashville, TN, USA

    Haydar Frangoul

  7. Division of Hematology Oncology, Department of Pediatrics, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, USA

    Gregory Yanik

  8. Department of Pharmacy and Research Institute, The Hospital for Sick Children, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

    L. Lee Dupuis

  9. Pediatric Hematology, Oncology and Stem Cell Transplantation, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Morris Kletzel

  10. Division of Hematology/Oncology/Bone Marrow Transplantation Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA

    Mark Ranalli

  11. Division of Stem Cell Transplant, Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, CA, USA

    Sandeep Soni

  12. Division of Oncology, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA

    Alix E. Seif & Stephan Grupp

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  1. Tal Schechter
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Correspondence to Tal Schechter.

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Conflict of interest

CCD has served on advisory boards and consulted for Jazz Pharmaceuticals (manufacturer of defibrotide). The other authors declare that they have no conflict of interest.

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Schechter, T., Perez-Albuerne, E., Lin, T.F. et al. Veno-occlusive disease after high-dose busulfan–melphalan in neuroblastoma. Bone Marrow Transplant 55, 531–537 (2020). https://doi.org/10.1038/s41409-018-0298-y

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