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FLAG-sequential regimen followed by bone marrow transplantation for myelodysplastic syndrome or acute leukemia in patients with Fanconi anemia: a Franco-Brazilian study

Bone Marrow Transplantation volume 56, pages 285–288 (2021)Cite this article

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Fanconi anemia (FA) is characterized by progressive bone marrow failure (BMF) and possible clonal evolution [1]. Clonal evolution into myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 30% of FA patients by the age of 40 years [2], associated with an adverse outcome. Clonal evolution in FA frequently involves a gain of 1q and 3q, deletion of 7q, and RUNX1 gene abnormalities [3]. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment in FA patients with BMF or clonal evolution [4, 5]. Currently, standard HSCT in first-line offers 30% overall survival (OS) for patients with advanced MDS or AML in FA [4, 6]. A sequential regimen was used with success in non-FA refractory leukemia before HSCT [7]. For FA patients with highly prone to radiotherapy and chemotherapy-induced toxicities, we reported an adapted FLAG-sequential regimen in six FA patients [8]. After a median follow-up of 28 months, all patients were alive, but with a more extended follow-up, two patients died. We thus updated previously reported cases and added new patients treated according to this approach in France and Brazil.

The study was conducted on behalf of the French reference center for aplastic anemia in collaboration with the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and with Curitiba and São Paulo hospitals. We retrospectively analyzed the characteristics and outcomes of confirmed MDS/AML/Acute lymphoid leukemia (ALL) for FA patients who received a FLAG-sequential regimen before HSCT between 2006 and 2019 (Supplementary Methodology). Patients with cytogenetic abnormalities only and marrow blast excesses less than 5% were not included. The primary outcome was 3years-OS. This study has been conducted in compliance with the Declaration of Helsinki and with the authorization of CNIL (number 2213438).

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Acknowledgements

The authors thank the patients, their families, and the “Association Française de la Maladie de Fanconi” (https://www.fanconi.com/). The authors would like to thank members of the Société Française de Greffe de Moelle et de Thérapie cellulaire (SFGM‐TC), the SFGM‐TC data manager Nicole Raus and all collaborators who contributed to patients recruitment, data registration, and quality control. The authors thank the nurses and physicians who cared for these patients and their families. This study has been conducted in compliance with the Declaration of Helsinki.

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Authors and Affiliations

  1. Hematology and Transplantation Unit, Saint-Louis Hospital, Paris, France

    P. E. Debureaux, F. Sicre de Fontbrune, G. Socie & R. Peffault de Latour

  2. Bone Marrow Transplantation Unit and Federal University of Paraná, Curitiba, Brazil

    C. Bonfim

  3. Hematology Unit, Robert Debré Hospital, Paris, France

    J. H. Dalle & T. Leblanc

  4. Pediatrics Immuno-Hematology Unit, Charles Nicolle Hospital, Rouen, France

    N. Buchbinder

  5. IHOPE, Civil Hospital of Lyon, Lyon, France

    Y. Bertrand & C. Renard

  6. Claude Bernard University, Lyon, France

    Y. Bertrand & C. Renard

  7. Hematology Unit, Haut-Levêque Hospital, Bordeaux, France

    E. Forcade

  8. Hematology Unit, University of São Paulo, São Paulo, Brazil

    J. Fernandes

  9. Clinical Immunology Unit, Saint-Louis Hospital, Paris, France

    A. Talbot

  10. INSERM UMR 976, Paris, France

    A. Talbot & G. Socie

  11. Bone Marrow Transplantation Unit, Hospital Nossa Senhora das Graças, Curitiba, Brazil

    R. Pasquini

  12. Hematology Laboratory, Saint-Louis Hospital, Paris, France

    J. Soulier

  13. University of Paris, Paris, France

    J. Soulier & G. Socie

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  1. P. E. Debureaux
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  2. F. Sicre de Fontbrune
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  12. J. Soulier
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  14. G. Socie
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  15. R. Peffault de Latour
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Correspondence to P. E. Debureaux.

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Debureaux, P.E., Sicre de Fontbrune, F., Bonfim, C. et al. FLAG-sequential regimen followed by bone marrow transplantation for myelodysplastic syndrome or acute leukemia in patients with Fanconi anemia: a Franco-Brazilian study. Bone Marrow Transplant 56, 285–288 (2021). https://doi.org/10.1038/s41409-020-0994-2

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  • DOI: https://doi.org/10.1038/s41409-020-0994-2

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