Cytogenetic studies of long-term survivors of childhood XXXX : a follow-up report.

@entity1 @entity981 @entity5 @entity74 @entity2008
Previous series including our earlier study of survivors of childhood @entity981 have documented the presence of nonclonal chromosome abnormalities in peripheral blood lymphocytes. To investigate whether or not these abnormalities persist, we restudied nine @entity1 , all of whom had received radiotherapy and a minimum of 3 years of systemic chemotherapy. Therapy had been discontinued a median of 3.9 years prior to study in our first report and a median of 7.2 years prior to study in this follow-up report. Thirty metaphases from short-term cultures of phytohemagglutinin-stimulated peripheral blood from each of nine @entity1 and nine matched controls were analyzed using G-banding. @entity2008 were present in cells from six of the nine @entity1 and 3.0% of @entity1 ' cells overall, as compared to seven of ten @entity1 and 3.5% of @entity1 ' cells in the earlier study. All @entity1 studied twice had abnormalities on one or both occasions. No evidence for the development of cytogenetically abnormal clones was found. Combined data from the two evaluations indicate that all of the @entity1 have a small population of long-lived lymphocytes with nonclonal chromosome abnormalities, the frequency of these cells appears to remain remarkably constant over time, and the proportion of cells with chromosome abnormalities is approximately threefold greater in @entity1 than in controls. It has become apparent that survivors of @entity981 are at increased risk for development of second @entity5 . The relationship between therapy-induced chromosome damage and the development of second @entity5 is currently unknown. We speculate that some cells, possibly in tissues other than peripheral blood, are preneoplastic by virtue of therapy-induced chromosome rearrangements involving critical genes and, following a long latent period, may undergo subsequent genetic or cellular changes that result in malignant transformation. Unfortunately, however, estimation of @entity74 through cytogenetic studies of peripheral blood T-lymphocytes does not appear to be a useful method for prediction of second @entity5 following @entity981 , since most or all of the @entity1 have a low level of abnormal cells.
