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Biol Blood Marrow Transplant. 2015 Oct;21(10):1796-801. doi: 10.1016/j.bbmt.2015.07.006. Epub 2015 Jul 14.

Preemptive Bone Marrow Transplantation for FANCD1/BRCA2.

Author information

1
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
2
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
3
Health Sciences Informatics, Johns Hopkins School of Medicine, Baltimore, Maryland.
4
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Electronic address: alterb@mail.nih.gov.

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.

KEYWORDS:

BRCA2; Decision analysis; Fanconi anemia; Markov model; Preemptive transplantation

PMID:
26183081
PMCID:
PMC4568159
DOI:
10.1016/j.bbmt.2015.07.006
[Indexed for MEDLINE]
Free PMC Article

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