Journal
BLOOD
Volume 101, Issue 4, Pages 1249-1256Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2002-07-2170
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA82678, 5T32 CA09685] Funding Source: Medline
- NCRR NIH HHS [M01-RR06020, M01-RR00102] Funding Source: Medline
- NHLBI NIH HHS [R37 HL32987] Funding Source: Medline
Ask authors/readers for more resources
Fanconi anemia (IFA) 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. (C) 2003 by The American Society of Hematology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available