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Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant
Authors:Maura Faraci  Tamara Diesch  Myriam Labopin  Arnaud Dalissier  Arian Lankester  Andrew Gennery  Mikael Sundin  Duygu Uckan-Cetinkaya  Marc Bierings  Anke M.J. Peters  Martina Garwer  Ansgar Schulz  Gerard Michel  Giovanna Giorgiani  Bernd Gruhn  Franco Locatelli  Stefano Giardino  Anne Uyttebroeck  Peter Bader  
Affiliation:1. Istituto G. Gaslini, Hematopoietic Stem Cell Transplantation Unit- Hematology-Oncology, Genova, Italy;2. University Children''s Hospital Basel, Division of Pediatric Oncology/Hematology, Basel, Switzerland;3. H?pital Saint-Antoine, Department of Hematology and Cell Therapy, Paris, France;4. EBMT Paris Study Office/CEREST-TC, Saint Antoine Hospital, Department of Hematology, Paris, France;5. Willem-Alexander Children''s Hospital, Leiden University Medical Center, Department of Pediatric Stem Cell Transplantation, Leiden, Netherlands;6. Children''s Hospital Newcastle upon Tyne, Pediatric Team Children''s BMT Unit, Newcastle upon Tyne, United Kingdom;7. Astrid Lindgren Children''s Hospital, Karolinska University Hospital, Hematology/Immunology Section, Stockholm, Sweden;8. Hacettepe University Faculty of Medicine, Bone Marrow Transplantation Unit, Department of Pediatrics, Ankara, Turkey;9. Princess Maxima Centre for Pediatric Oncology and University Children''s Hospital, Utrecht, Netherlands;10. Medical Center, University of Freiburg, Center for Pediatrics, Department of Pediatric Hematology and Oncology, Freiburg, Germany;11. University Hamburg-Eppendorf, Pediatric Hematology Clinic and Policlinic of Oncology, Hamburg-Eppendorf, Germany;12. University Medical Center Ulm, Department of Pediatrics, Ulm, Germany;13. Hopital d''Enfants de la Timone Marseille, Marseille, France;14. Fondazione IRCCS Policlinico San Matteo, Pediatric Hematology-Oncology, Pavia, Italy;15. Jena University Hospital, Department of Pediatrics, Jena, Germany;16. IRCSS Ospedale Pediatrico Bambino Gesù, University La Sapienza, Department of Pediatric Hematology/Oncology, Rome, Italy;17. University Hospitals Leuven, Department of Pediatric Hematology-Oncology, Leuven, Belgium;18. Pediatric BMT Unit, Nantes, France;19. Turku University Hospital, Children''s Hospital, Turku, Finland;20. University of Heidelberg, Heidelberg, Germany;21. The Children''s Hospital at Westmead, Division of Blood and Marrow Transplantation, Sydney, Australia;22. Ghent University Hospital, Department of Pediatric Hematology, Oncology and SCT, Ghen, Belgium;23. University Children''s Hospital Würzburg, Department of Pediatric Oncology, Würzburg, Germany;24. The Queen Silvia''s Hospital for Children and Adolescents, University of Göteborg, Pediatric Hematology and Oncology, Göteborg, Sweden;25. Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, University of Murcia, Barcelona, Spain;26. Sheffield Children''s Hospital, Department of Hematology and Oncology, Sheffield, United Kingdom;27. Pediatric Hemato-Oncology Department, University Hospital, Rouen, Rouen, France;28. Bordeaux University Hospital, Pediatric BMT Unit, Bordeaux, France;29. St. Anna Children''s Hospital, Medical University Vienna, Vienna, Austria;30. Imperial College London, Department of Medicine, London, United Kingdom;31. Medical University of Warsaw, Department of Hematology, Oncology and Internal Medicine, Warsaw, Poland;32. University of Regensburg, Department of Pediatric Hematology, Oncology & Stem Cell Transplantation, Regensburg, Germany;33. Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain;34. Goethe-Universität, Universitätsklinikum Frankfurt, Frankfurt, Germany
Abstract:Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population.
Keywords:Correspondence and reprint requests: Maura Faraci, MD, Hematology/Oncology – Stem Cell Transplantation Unit, Istituto G. Gaslini, Largo G. Gaslini, 5   16147 Genova, Italy.  Gonadal damage  Busulfan  Treosulfan  Pubertal stage
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