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Recent results of hematopoietic stem cell transplantation for thalassemia with busulfan-based conditioning regimen in France: improved thalassemia free survival despite frequent mixed chimerism. A retrospective study from the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Bone Marrow Transplantation volume 58, pages 1254–1256 (2023)Cite this article

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Transfusion-dependent thalassemia(TDT) is a severe anemia due to the reduction or absence of globin chains synthesis requiring red blood cell transfusion from infancy [1]. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment available in current practice and HSCT using myeloablative conditioning (MAC) regimen is a standard of care for TDT children having a matched sibling donor (MSD) [2]. A previous study from the French society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC) reported an overall survival (OS) of 86.8% in TDT patients transplanted in France between 1985–2007 mainly with MSD and MAC regimen based on busulfan and cyclophosphamide (BuCy) [3]. Thalassemia free survival (TFS) improved with time up to 83% concomitantly to the introduction of anti-thymocyte globulins (ATG, Thymoglobulin®). We now report HSCT results using Bu-based MAC regimen and in almost all cases ATG, in TDT patients treated between 2008 and 2018, with an emphasis on anemia correction and donor chimerism.

All TDT patients (n = 63) transplanted in the 15 participating centers were included. Patients were identified and data were extracted from the European Society for Blood and Marrow Transplantation database managed by the SFGM-TC. Patients or their legal guardians signed informed consent forms authorizing the inclusion of personal information for research purposes. Chimerism data were analyzed between 1–3 months (M1–3), 6–12 months (M6–12) and >1 year after HSCT (last chimerism evaluation). Donor chimerism was assessed on DNA extracted from whole blood using short-tandem repeat PCR (detection limit between 2 and 5%) or higher sensitivity real-time quantitative PCR completed with short-tandem repeat PCR in case of donor chimerism between 10 and 90% of donor cells depending on the center.

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Acknowledgements

We thank the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC), Nicole Raus (data manager of the SFGM-TC) and the Rare Disease Center for Thalassemia from Marseille. We also thank the clinicians participating in the registry and the patients and their families.

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Authors and Affiliations

  1. Department of Pediatric Hematology, Robert Debré Hospital, GHU APHP Nord, Université Paris Cité, Paris, France

    Marica Rossi, Karima Yakouben & Jean-Hugues Dalle

  2. Department of Pediatric Hematology and Oncology, Rare Disease Center for Thalassemia, La Timone Hospital, Marseille, France

    Sarah Szepetowski, Gérard Michel & Isabelle Thuret

  3. Department of Pediatric Hematology and Oncology, Hautepierre Hospital, Strasbourg, France

    Catherine Paillard

  4. Department of Pediatric Hematology and Oncology, Arnaud de Villeneuve Hospital, Montpellier, France

    Anne Sirvent

  5. Department of Pediatric Immunology and Hematology, Necker-Enfants Malades Hospital, Paris, France

    Martin Castelle

  6. Department of Pediatric Hematology and Oncology, Estaing Hospital, Clermont-Ferrand, France

    Charline Pegon

  7. Department of Pediatric Hematology and Oncology, Mother and Child University Hospital, Limoges, France

    Christophe Piguet

  8. Department of Pediatric Hematology and Oncology, University Hospital of Nantes, Nantes, France

    Audrey Grain

  9. Department of Pediatric Hematology and Oncology, Pellegrin Hospital, Bordeaux, France

    Marie Angoso

  10. Department of Stem Cell Transplantation, Saint-Louis Hospital, GHU APHP Nord, Université Paris Cité, Paris, France

    Marie Robin

  11. Unit of Hematology for Adolescents, Saint-Louis Hospital, Paris, France

    Nathalie Dhedin

  12. Rare Disease Center for Sickle Cell Disease, Centre Hospitalier Intercommunal de Créteil, Créteil, INSERM U955, Paris Est Créteil University, Créteil, France

    Corinne Pondarré

  13. Department of Pediatric Hematology and Oncology, Charles Nicolle Hospital, Rouen, France

    Cécile Dumesnil de Maricourt

  14. Department of Adult Hematology, Jean Minjoz Hospital, Besançon, France

    Ana Berceanu

  15. Department of Pediatric Hematology and Oncology, Jean Minjoz Hospital, Besançon, France

    Pauline Simon

  16. Department of Adult Hematology, Necker-Enfants Malades Hospital, Paris, France

    Ambroise Marcais

  17. Department of Pediatric Hematology and Oncology, University Hospital of Nice, Nice, France

    Maryline Poirée

  18. Department of Pediatric Hematology and Oncology, University Hospital of Rennes, Rennes, France

    Virginie Gandemer

  19. Department of Pediatric Hematology and Oncology, University Hospital of Grenoble, Grenoble, France

    Dominique Plantaz

  20. Department of Hematology, La Pitié-Salpêtrière Hospital, Paris, France

    Stéphanie Nguyen

  21. Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC), Paris, France

    Stéphanie Nguyen

  22. Unit for Clinical and Epidemiological Research, DRRC/AP-HM Faculté de Médecine de Marseille, Marseille, France

    Anderson Loundou

Authors
  1. Marica Rossi
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  2. Sarah Szepetowski
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  3. Karima Yakouben
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  6. Martin Castelle
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  7. Charline Pegon
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  8. Christophe Piguet
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  9. Audrey Grain
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  10. Marie Angoso
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  11. Marie Robin
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  14. Cécile Dumesnil de Maricourt
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  15. Ana Berceanu
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  16. Pauline Simon
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  17. Ambroise Marcais
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  18. Maryline Poirée
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  19. Virginie Gandemer
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  20. Dominique Plantaz
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  21. Stéphanie Nguyen
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  22. Gérard Michel
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  23. Anderson Loundou
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  24. Jean-Hugues Dalle
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  25. Isabelle Thuret
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Contributions

M. Rossi and IT were the principal investigators, designed the study, collected and analyzed the data and wrote the paper. AL performed the statistical analysis. All authors contributed to the critical revision and approved the final version of the manuscript.

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Correspondence to Marica Rossi.

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Rossi, M., Szepetowski, S., Yakouben, K. et al. Recent results of hematopoietic stem cell transplantation for thalassemia with busulfan-based conditioning regimen in France: improved thalassemia free survival despite frequent mixed chimerism. A retrospective study from the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant 58, 1254–1256 (2023). https://doi.org/10.1038/s41409-023-02079-0

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  • DOI: https://doi.org/10.1038/s41409-023-02079-0

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