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Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial

Bone Marrow Transplantation volume 57, pages 1698–1703 (2022)Cite this article

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Abstract

Data regarding the safety and efficacy of reduced-toxicity conditioning regimen (RTC) prior to allogeneic stem cell transplantation (allo-SCT) to treat hematological malignancies in pediatric patients are limited. This prospective multicenter, phase 2 trial investigated a RTC regimen based on the combination of intravenous busulfan (3.2 mg/kg/d x 4 days), fludarabine (30 mg/m2/d x 5 days) and antithymocyte globulin (Thymoglobulin®, Genzyme; 5 mg/kg total dose) with the aim of delivering high dose myeloablation that would allow optimal disease control while minimizing toxicity, in a subgroup of children at very high risk of non-relapse mortality (NRM). The primary endpoint was NRM at 1 year after allo-SCT. A total of 48 high risk patients were included (median age, 13 years; range, 3–24). At 1 year, the cumulative incidence of recurrence/disease progression and NRM were 33% and 8%, respectively. With a median follow-up of 23 months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) at 1 year were 69% and 58%, respectively. We conclude that the RTC regimen used in this prospective trial is safe, with a < 10% NRM rate noted among high-risk children and adolescents, paving the way for larger phase 3 trials incorporating novel agents pre- and post-allo-SCT.

(ClinicalTrials.gov Identifier: NCT01572181)

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Fig. 1: Outcome after allo-HSCT.

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Data availability

Data are available upon request to ML or MM.

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Acknowledgements

This trial was supported by the French national cancer institute (INCa) through a grant as part of the “Programme Hospitalier de Recherche Clinique” (PHRC-Cancer)

Author information

Authors and Affiliations

  1. CHU de Nantes, Nantes, France

    Fanny Rialland & Audrey Grain

  2. Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France

    Myriam Labopin, Eolia Brissot & Mohamad Mohty

  3. Department of Pediatric Immunology, Hematology and Oncology, Timone Enfants Hospital and Aix-Marseille University, Marseille, France

    Gerard Michel

  4. University hospital of Rennes, University of Rennes1, Rennes, France

    Virginie Gandemer

  5. Department of Paediatric Haematology and Oncology, Strasbourg University Hospital, Strasbourg, France

    Catherine Paillard

  6. Hôpital Brabois, Nancy, France

    Cécile Pochon

  7. CHU Bordeaux, Bordeaux, France

    Laurence Clement & Charlotte Jubert

  8. University Hospital, Montpellier, France

    Anne Sirvent

  9. Nice University Hospital, Nice, France

    Pierre Simon Rohrlich

  10. University Hospital of Grenoble, La Tronche, France

    Dominique Plantaz

  11. Hôpital Robert Debré, GH APHP Nord - Université de Paris, Paris, France

    Jean-Hugues Dalle

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  1. Fanny Rialland
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Contributions

MM, ML, and FR designed the research, collected and analyzed the data, and wrote the paper. All co-authors enrolled and treated patients, and participated in the manuscript. All co-authors approved the paper.

Corresponding author

Correspondence to Fanny Rialland.

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Competing interests

MM has received lecture honoraria and research support from Pierre-Fabre Medicament, and Sanofi whose products are studied here. FR: none. ML: none. JHD: received honoraria and research financial support from Sanofi.

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Rialland, F., Grain, A., Labopin, M. et al. Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial. Bone Marrow Transplant 57, 1698–1703 (2022). https://doi.org/10.1038/s41409-022-01769-5

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