title: A 20-year perspective on the International Fanconi Anemia Registry (IFAR).
abstract: Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents and cancer predisposition. Recent evidence for the interactions of ataxia-telangiectasia mutated protein ATM and breast cancer susceptibility proteins BRCA1 and BRCA2 (identified as FANCD1) with other known FA proteins suggests that FA proteins have a significant role in DNA repair/recombination and cell cycle control. The International Fanconi Anemia Registry (IFAR), a prospectively collected database of FA patients, allows us the unique opportunity to analyze the natural history of this rare, clinically heterogeneous disorder in a large number of patients. Of the 754 subjects in this study, 601 (80%) experienced the onset of bone marrow failure (BMF), and 173 (23%) had a total of 199 neoplasms. Of these neoplasms, 120 (60%) were hematologic and 79 (40%) were nonhematologic. The risk of developing BMF and hematologic and nonhematologic neoplasms increased with advancing age with a 90%, 33%, and 28% cumulative incidence, respectively, by 40 years of age. Univariate analysis revealed a significantly earlier onset of BMF and poorer survival for complementation group C compared with groups A and G; however, there was no significant difference in the time to hematologic or nonhematologic neoplasm development between these groups. Multivariate analysis of overall survival time shows that FANCC mutations (P =.007) and hematopoietic stem cell transplantation (P = <.0001) define a poor-risk subgroup. The results of this study of patients registered in the IFAR over a 20-year period provide information that will enable better prediction of outcome and aid clinicians with decisions regarding major therapeutic modalities.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Kutler
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
authors.forename: Jaya
authors.initials: J
authors.lastname: Satagopan
authors.forename: Sat Dev
authors.initials: SD
authors.lastname: Batish
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: Philip F
authors.initials: PF
authors.lastname: Giampietro
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
mesh_terms: D001855:Bone Marrow Diseases / Q000150:complications; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000628:therapy; D005260:Female; D005838:Genotype; D019337:Hematologic Neoplasms / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007391:International Cooperation; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology; D010641:Phenotype; D011379:Prognosis; D012042:Registries; D012727:Sex Characteristics; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors