title: Four decades of stem cell transplantation for Fanconi anaemia in the Netherlands.
abstract: This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty-two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m(2) and cyclophosphamide 30 mg/kg ± anti-thymocyte globulin - no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow-up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation-wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non-irradiation and busulfan-free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder.
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Smetsers
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Smiers
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Dorine
authors.initials: D
authors.lastname: Bresters
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Martine C
authors.initials: MC
authors.lastname: Sonnevelt
authors.affiliation: Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre Utrecht, Utrecht, The Netherlands.|Dutch Childhood Oncology Group, Fanconi Anaemia Guideline Chair, The Hague, The Netherlands.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bierings
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009026:Mortality; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
keywords: Fanconi anaemia; bone marrow failure; chemosensitivity; leukaemia; stem cell transplantation