title: Preemptive Bone Marrow Transplantation for FANCD1/BRCA2.
abstract: Children with biallelic mutations in FANCD1/BRCA2 are at uniquely high risks of leukemia and solid tumors. Preemptive bone marrow transplantation (PE-BMT) has been proposed to avoid the development of leukemia, but empirical study of PE-BMT is unlikely because of the rarity of these children and the unknown benefit of PE-BMT. We used survival analysis to estimate the risks of leukemia and the expected survival if leukemia could be eliminated by curative PE-BMT. We used the results in a decision analysis model to explore the plausibility of PE-BMT for children with variable ages at diagnosis and risks of transplantation-related mortality. For example, PE-BMT at 1 year of age with a 10% risk of transplantation-related mortality increased the mean survival by 1.7 years. The greatest benefit was for patients diagnosed between 1 and 3 years of age, after which the benefit of PE-BMT decreased with age at diagnosis, and the risk of death from solid tumors constituted a relatively greater burden of mortality. Our methods may be used to model survival for other hematologic disorders with limited empirical data and a pressing need for clinical guidance.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Khan
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.affiliation: Health Sciences Informatics, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Harold P
authors.initials: HP
authors.lastname: Lehmann
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Electronic address: alterb@mail.nih.gov.
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D016026:Bone Marrow Transplantation / Q000401:mortality; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003661:Decision Support Techniques; D024522:Genes, BRCA2; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D008390:Markov Chains; D008962:Models, Theoretical; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011788:Quality of Life; D012306:Risk; D019172:Transplantation Conditioning / Q000009:adverse effects
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA2; Decision analysis; Fanconi anemia; Markov model; Preemptive transplantation