Therapy-Related Chronic Myeloid Leukemia: An Epidemiological, Clinical and Pathogenetic Appraisal

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Abstract
Second primary cancers represent an important complication of modern chemotherapy and radiotherapy. Therapy-related (tr) leukemias are among the most common second malignancies in both pediatric and adult populations. Whereas a reasonable amount of data is available regarding the epidemiology, molecular pathogenesis, clinical behavior and response to therapy of second primary acute leukemias, very little is known about therapy-related chronic myeloid leukemia (tr-CML). A better characterization of this entity could increase our understanding about the mechanisms of carcinogenesis, specially the induction of specific genetic abnormalities, e.g., BCR-ABL fusion, following chemotherapy and/or radiotherapy exposure, could facilitate the investigation of the kinetics of the development of CML, and also provide a model to study molecular events that might precede its development. Review of 32 tr-CML cases suggests that there are no clinically appreciable differences between tr-CML and de novo CML cases. Analysis of large epidemiological studies that investigated the risk of second primary leukemias has not shown any clear evidence of a higher risk of CML among individuals who underwent treatment for a primary cancer over the general population. The cancer-predisposing syndromes, the detection of BCR-ABL transcripts in healthy individuals, and the induction in vitro of BCR-ABL fusions by ionizing radiation, are all discussed in the context of tr-CML. Finally, the need for a large epidemiological study to specifically assess the risk of developing second primary CML after chemotherapy and/or radiotherapy is stressed.