title: Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan.
abstract: The occurrence of late sequelae after myeloablative conditioning regimens for stem-cell transplantation (SCT) has prompted the introduction of reduced-intensity chemotherapy (RIC) regimens in an attempt to reduce toxicity and spare fertility. We retrospectively evaluated gonadal function in survivors of SCT in childhood by comparing patients conditioned with a myeloablative regimen containing busulfan and cyclophosphamide (BuCy, N = 51, 28 boys) and a RIC regimen containing fludarabine and melphalan (FluMel, N = 40, 19 boys). Spontaneous puberty occurred in 56% of girls and 89% of boys after BuCy, whereas 90% of females and all males in the FluMel group entered puberty spontaneously (P = 0·012). Significantly more females (61%) conditioned with BuCy required hormone replacement compared with the FluMel group (10·5%, P = 0·012). Females in the FluMel group took significantly longer to develop elevation of serum follicle-stimulating hormone (FSH) concentrations (>10 iu/l) from the onset of puberty than females in the BuCy group (median 5·2 years vs. 2·7 years respectively, P = 0·0135). In males no difference was noted between the two conditioning groups in time to FSH elevation (median 4 years in FluMel versus 6 years in BuCy). Whilst the two regimens have similar effects on the testis, ovarian function seems to be better preserved in females undergoing SCT with RIC.
authors.affiliation: Department of Pediatric Oncology and Haematology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Panasiuk
authors.affiliation: Department of Endocrinology, St George's Hospital Medical School, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Nussey
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.|Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Section, UCL Institute of Child Health, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.|Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Section, UCL Institute of Child Health, London, UK.
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.affiliation: Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.affiliation: Department of Pediatric Oncology and Haematology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Maryna
authors.initials: M
authors.lastname: Krawczuk-Rybak
authors.affiliation: Department of Haematology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Leiper
mesh_terms: D000293:Adolescent; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects*; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D010053:Ovary / Q000378:metabolism*; D011627:Puberty / Q000187:drug effects*; D012189:Retrospective Studies; D012727:Sex Characteristics; D033581:Stem Cell Transplantation; D013737:Testis / Q000378:metabolism*; D019172:Transplantation Conditioning / Q000009:adverse effects*
chemical_list: D019653:Myeloablative Agonists; D005640:Follicle Stimulating Hormone; D002066:Busulfan; D008558:Melphalan
keywords: children; fertility; gonadal function; melphalan; stem cell transplantation