THERAPY-RELATED CHRONIC MYELOID-LEUKEMIA - AN EPIDEMIOLOGIC, CLINICALAND PATHOGENETIC APPRAISAL

Second primary cancers represent an important complication of modern c hemotherapy and radiotherapy. Therapy-related (tr) leukemias are among the most common second malignancies in both pediatric and adult popul ations. 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 abo ut therapy-related chronic myeloid leukemia (tr-CML). A better charact erization of this entity could increase our understanding about the me chanisms of carcinogenesis, specially the induction of specific geneti c abnormalities, e.g., BCR-ABL fusion, following chemotherapy and/or r adiotherapy exposure, could facilitate the investigation of the kineti cs of the development of CML, and also provide a model to study molecu lar events that might precede its development. Review of 32 tr-CML cas es suggests that then are no clinically appreciable differences betwee n tr-CML and de novo CML cases. Analysis of large epidemiological stud ies that investigated the risk of second primary leukemias has not sho wn any clear evidence of a higher risk of CML among individuals who un derwent treatment for a primary cancer over the general population. Th e 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. Fin ally, the need for a large epidemiological study to specifically asses s the risk of developing second primary CML after chemotherapy and/or radiotherapy is stressed.