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Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia

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Abstract

Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3 years was 51 % and not significantly influenced by number of HSCT (first HSCT 54 %, ≥second HSCT 44 %, p = 0.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p = 0.04 and 0.004). Treatment-related mortality was low at 14 %. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.

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Acknowledgments

We thank Arnaud Dalassier for data correction and management.

Conflict of interest

The EBMT received an unrestricted grant for the retrospective data collection and analysis from medac GmbH. CP received travel grants and study support from medac, Pierre Fabre, Sanofi and Novartis. HB received a travel grant from Pierre Fabre. KWS received travel grants and study support from medac.

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Authors and Affiliations

  1. St. Anna Kinderspital and Children’s Cancer Research Institute, Department of Paediatrics, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria

    Heidrun Boztug, Ulrike Pötschger, Evgenia Glogova & Christina Peters

  2. Paediatric Haematology/Oncology, Fondazione IRCCS, Policlinico San Matteo Foundation, Pavia, Italy

    Marco Zecca

  3. Department of Paediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany

    Karl-Walter Sykora

  4. Great Ormond Street Hospital for Children National Health Service Trust, London, UK

    Paul Veys

  5. Department of Paediatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands

    Arjan Lankester

  6. Paediatric Immunology Department, Great North Children’s Hospital, Newcastle upon Tyne, UK

    Mary Slatter

  7. Department of Paediatric and Adolescent Haematology and Oncology, and Children’s HSCT Unit, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, UK

    Roderick Skinner

  8. Department of Paediatric Haematology, Oncology, and Haematopoietic Stem Cell Transplantation, University of Medical Sciences, Poznań, Poland

    Jacek Wachowiak

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  1. Heidrun Boztug
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on behalf of the EBMT paediatric diseases working party

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Correspondence to Heidrun Boztug.

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Boztug, H., Zecca, M., Sykora, KW. et al. Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia. Ann Hematol 94, 297–306 (2015). https://doi.org/10.1007/s00277-014-2196-8

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  • DOI: https://doi.org/10.1007/s00277-014-2196-8

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