The occurrence of acute leukemia after treatment of a primary malignancy is a problem of increasing concern to clinical oncologists. It is not clear if these patients are particularly cancer-prone, or if the treatment regimen, radiation, chemotheraphy, or a combination of the two, induces the leukemic transformation. I have just completed the chromosome analysis with banding of leukemic cells from 47 patients with acute nonlymphocytic leukemia or dysmyelopoietic syndrome following treated lymphoma, other malignancies, or renal transplantation. With three exceptions, each of these patients had a chromosomaly abnormal clone of cells; loss of chromosomes Nos. 5 and/or 7 was seen in 39 of 44 aneuploid patients. Careful analysis of deletions of No. 7 indicates that the critical region associated with leukemia is 7q32 to the end; a similar analysis of No. 5 will define the critical segment for that chromosome. In our 47 patients, the median time for the onset of marrow dysplasia was 56 months following diagnosis of the primary disease. Thirty-two patients had a preleukemic phase 2-20 months prior to overt leukemia. I will study the role of previous malignancy and type of therapy by analysing bone marrow chromosomes in four groups of patients receiving cytotoxic therapy: (1) malignant lymphoma, (2) breast cancer, (3) gynecological malignancies, and (4) post-renal transplant. Study of the increase of sister chromatid exchanges in the cells of patients with myelodysplasia and with suitably matched controls will establish whether the former seem to be significantly more sensitive to mutagenic exposure than do the latter patients. This investigation will establish whether nonrandom chromosome changes can be detected prior to the development of leukemia, whether the frequency and type of abnormality is different in the various clinical groups, or can be related to the type of treatment regimen. The percentage of chromosomally abnormal myeloid cells and the complexity of the chromosome changes in the preleukemic phase would be correlated with overall survival to see if either or both have prognostic significance. This study will contribute to our understanding of the role of chromosome abnormalities in leukemogenesis, and will permit the earlier detection of patients at risk.
