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Busulfan–Melphalan followed by autologous stem cell transplantation in patients with high-risk neuroblastoma or Ewing sarcoma: an exposed–unexposed study evaluating the clinical impact of the order of drug administration

Bone Marrow Transplantation volume 51, pages 1265–1267 (2016)Cite this article

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High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) have improved the prognosis of high-risk neuroblastoma and metastatic Ewing sarcoma.1, 2 The impact of the drugs in the HDC regimen was first demonstrated in a study performed in the Gustave Roussy Pediatrics Department. It showed improved survival for patients with stage 4 neuroblastoma who received a combination of busulfan (Bu) and melphalan (Mel).3 These results were confirmed in a European randomized study (HR-NBL1/SIOPEN), and this combination is now administered worldwide to patients with high-risk neuroblastoma.4, 5 This HDC was used as a consolidation regimen in metastatic Ewing sarcoma and proved beneficial for event-free survival (EFS).6

However, the toxicity of Bu–Mel is severe with specific endothelial toxicity and a high rate of hepatic veno-occlusive disease (VOD), non-infectious interstitial pneumonitis or pulmonary hypertension. Reducing the incidence of these complications remains a major issue for the future strategy for administering this regimen. Preclinical and clinical studies suggest that the order of administering alkylating agents can influence the toxicity of HDC. When Bu is given first in combination with another alkylating agent, it can increase the toxicity of the second drug by inducing glutathione depletion and/or lower the metabolism of the second chemotherapeutic agent.7, 8

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Acknowledgements

We are grateful to Lorna Saint Ange for editing. We thank Pierre Fabre Medicament who provided financial research support for the current study but did not participate in the conduct of the study or data analyses.

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Authors and Affiliations

  1. Département de Cancérologie de l’Enfant et de l’Adolescent, Gustave Roussy, Université Paris-Saclay, Villejuif, France

    M E Dourthe, C Dufour & D Valteau-Couanet

  2. Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d’Epidémiologie, Villejuif, France

    N Ternès, D Gajda & E Benhamou

  3. Gustave Roussy, Université Paris-Saclay, Service de Pharmacologie et d’analyse, Villejuif, France

    A Paci

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Correspondence to M E Dourthe.

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Dourthe, M., Ternès, N., Gajda, D. et al. Busulfan–Melphalan followed by autologous stem cell transplantation in patients with high-risk neuroblastoma or Ewing sarcoma: an exposed–unexposed study evaluating the clinical impact of the order of drug administration. Bone Marrow Transplant 51, 1265–1267 (2016). https://doi.org/10.1038/bmt.2016.109

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