Chromosome damage and second malignancy in patients treated with melphalan

Cytogenetic studies were carried out on peripheral lymphocytes from cancer patients at different times after therapy with melphalan. The frequency of sister chromatid exchange (SCE) was increased markedly shortly after treatment, and then declined to near pretreatment levels over a four-week period. In-vitro studies showed that the SCE frequency induced by melphalan is reduced slowly in resting G0 lymphocytes and considerably faster in mitogen-stimulated G1 cells. The results demonstrate that measurement of SCE is useful for the study of newly-induced chromosome damage in melphalan-treated cells, but is less suitable for the detection of persistent, cytogenetic alterations long after therapy. The frequency of chromosomal aberrations in a cohort of 50 patients with ovarian carcinoma was increased for up to ten years after melphalan therapy. The predominant aberrations were chromosomal translocations, marker chromosomes and cells with multiple, complex rearrangements. The frequency distribution of chromosomes involved in aberrations was studied in cells from some of the patients. An overrepresentation of chromosomes 8 and 9 was found in these cells, whereas the X chromosome was overrepresented in cells from control subjects. An increased frequency of chromosomal rearrangements was found in long-term cultures of T-lymphocytes from three of the patients, indicating that these aberrations are compatible with cell survival and proliferation. Seven patients in the cohort developed a second, primary tumour during the observation time. The frequencies and types of aberrations in these patients were similar to those of the other patients in the cohort.