NEW YORK (Reuters Health) - Children who undergo chemotherapy for acute lymphocytic leukemia have a 200-fold increase in the frequency of somatic mutations, according to a study from the University of Vermont.
In the July issue of Cancer Research, Dr. Sederick C. Rice and colleagues at the University’s medical school in Burlington note that while survival rates in pediatric cancer patients have increased in recent years, the long-term genotoxic effects of therapy have remained unclear.
Using 130 peripheral blood samples from 45 children treated for acute lymphocytic leukemia, the researchers analyzed changes in the frequency of somatic mutations at the hypoxanthine-guanine phophoribosyltransferase reporter gene.
During each phase of treatment - diagnosis, consolidation, maintenance, and off-therapy - the authors observed increases in the mean number of somatic mutations that were independent of whether the children were receiving treatment under low-, standard-, or high-risk group protocols.
An observed 200-fold increase in mean somatic mutations “remained elevated years after the completion of therapy,” according to the authors.
“To the best of our knowledge,” they write, “the increased frequency of mutations observed in these children is the highest recorded in humans after genotoxic exposure.”
In a press release from the American Association for Cancer Research, senior author Dr. Barry A. Finette notes that some of the earliest children to be cured of acute lymphocytic leukemia have now survived more than 10 and more recently even 15 years after therapy. These children have a 5-20 times greater risk of a second malignancy, Dr. Finette said in the press release.
“Combination chemotherapy used to treat children with acute lymphocytic leukemia is quite genotoxic,” the researchers conclude, and “may result in an elevated risk for the development of multi-factorial diseases, in particular second malignancies.”
Source: Cancer Res 2004;64:4464-4471. [ Google search on this article ]
MeSH Headings: Antineoplastic Agents, Combined : Leukemia, Lymphocytic, Acute
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