A 20-year perspective on the International Fanconi Anemia Registry (IFAR)

David I. Kutler, Bhuvanesh Singh, Jaya Satagopan, Sat Dev Batish, Marianne Berwick, Philip F. Giampietro, Helmut Hanenberg, Arlene D. Auerbach

Research output: Contribution to journalArticle

488 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1249-1256
Number of pages8
JournalBlood
Volume101
Issue number4
DOIs
StatePublished - Feb 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kutler, D. I., Singh, B., Satagopan, J., Batish, S. D., Berwick, M., Giampietro, P. F., Hanenberg, H., & Auerbach, A. D. (2003). A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood, 101(4), 1249-1256. https://doi.org/10.1182/blood-2002-07-2170