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Busulfan–fludarabine- or treosulfan–fludarabine-based myeloablative conditioning for children with thalassemia major

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Abstract

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients’ life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan–fludarabine-based and treosulfan–fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan–fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan–fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3–95.1%) after busulfan–fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7–96.6%) after treosulfan–fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.

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Author notes

  1. Roswitha Lüftinger, Natalia Zubarovskaya, Christina Peters, Arjan Lankester, and Selim Corbacioglu contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Stem Cell Transplantation, St. Anna Children’s Hospital, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria

    Roswitha Lüftinger, Natalia Zubarovskaya, Annamaria Cseh, Elisabeth Salzer & Christina Peters

  2. EBMT Statistical Unit, Pediatric Diseases Working Party, Paris, France

    Jacques-Emmanuel Galimard

  3. Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Franco Locatelli & Mattia Algeri

  4. Department of Pediatric Sciences, University of Pavia, Pavia, Italy

    Franco Locatelli

  5. Department of Pediatric Hematology and Stem Cell Transplantation Unit, Medical Park Antalya Hastanesi, Antalya, Turkey

    Akif Yesilipek

  6. Department of Pediatrics, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK

    Josu de la Fuente

  7. Fondiazione IME Policlinico Tor Vergata Rome, Rome, Italy

    Antonella Isgrò

  8. Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Amal Alseraihy

  9. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Emanuele Angelucci

  10. Department of Pediatrics, Division of Immuno-Hematology and Stem Cell Transplantation, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands

    Frans J. Smiers & Arjan Lankester

  11. Centro Trapianti, Unico Di CSE Adulti E Pediatrico A. O Brotzu, Cagliari, Italy

    Giorgia La La Nasa

  12. Fondazione IRCCS Policlinico San Matteo Pediatric Hematology-Oncology, Pavia, Italy

    Marco Zecca

  13. Altinbaş University, Faculty of Medicine, Bahçelievler Medical Park Hospital, Pediatric Bone Marrow Transplantation Unit, Istanbul, Turkey

    Tunc Fisgin

  14. Ankara University Pediatric BMT Unit, Ankara, Turkey

    Emel Unal

  15. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany

    Katharina Kleinschmidt & Selim Corbacioglu

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  1. Roswitha Lüftinger
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  2. Natalia Zubarovskaya
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on behalf of the EBMT Pediatric Diseases, Inborn Errors Working Parties

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Correspondence to Roswitha Lüftinger.

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Lüftinger, R., Zubarovskaya, N., Galimard, JE. et al. Busulfan–fludarabine- or treosulfan–fludarabine-based myeloablative conditioning for children with thalassemia major. Ann Hematol 101, 655–665 (2022). https://doi.org/10.1007/s00277-021-04732-4

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