title: Factors affecting the outcome of related allogeneic hematopoietic cell transplantation in patients with Fanconi Anemia.
abstract: Hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi Anemia (FA), and it is generally accepted that these patients should receive low-intensity conditioning because of the underlying DNA repair defect in their cells. Outcomes for recipients of matched related HCT have generally been favorable, but only a few studies have scrutinized the factors that may affect the eventual outcome of these patients. This retrospective analysis of 94 pediatric patients with FA who underwent related HCT at King Faisal Specialist Hospital & Research Center was carried out to attempt to identify factors that may affect outcome. Results showed overall survival (OS) probabilities of 92.5%, 89%, and 86% at 1, 5, and 10 years, respectively. In univariate analysis, use of higher dose cyclophosphamide (CY) (60 mg/kg) conditioning was associated with a better 10-year OS than lower dose CY (20 mg/kg) conditioning (91% versus 82%, respectively; P = .035), and use of radiation-containing regimens was associated with a significantly lower 10-year OS than nonradiation regimens (76% versus 91%, respectively; P = .005). Of the 4 regimens used in this study, the fludarabine-based regimen was associated with the highest survival (95.2%; P = .034). The use of the higher dose CY (60 mg/kg) was associated with a significantly increased incidence of hemorrhagic cystitis (HC) (20% versus 5.6% respectively; P = .049). Three patients (3%) developed squamous cell carcinoma (2 oropharyngeal and 1 genitourinary), at 9.4, 5.4, and 13.3 years after HCT; 2 of them had radiation-containing conditioning. In conclusion, our data suggest that although using a higher dose CY (60 mg/kg) conditioning regimen may be associated with better survival, it is also associated with a significantly increased risk of HC. The addition of fludarabine to the low-dose CY (20 mg/kg) is associated with the best survival. On the other hand, radiation-containing regimens are associated with significantly lower survival.
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Electronic address: mouhab@kfshrc.edu.sa.
authors: Mouhab
authors: M
authors: Ayas
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Khawar
authors: K
authors: Siddiqui
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Abdullah
authors: A
authors: Al-Jefri
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Hassan
authors: H
authors: El-Solh
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Ali
authors: A
authors: Al-Ahmari
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Ashraf
authors: A
authors: Khairy
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Samer
authors: S
authors: Markiz
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Hasan
authors: H
authors: Shahin
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Abdulrahman
authors: A
authors: Al-Musa
authors: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors: Amal
authors: A
authors: Al-Seraihy
mesh_terms: D000293:Adolescent; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects; D003556:Cystitis / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D005199:Fanconi Anemia / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000009:adverse effects; D009959:Oropharyngeal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Cyclophosphamide; Fanconi anemia; Radiation; Stem cell transplantation