Therapy-related chronic myeloid leukemia: an epidemiological, clinical and pathogenetic appraisal.
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.
Aguiar
R C
RC
LRF Centre for Adult Leukaemia, Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK. RicardovAguiar@dfci.harvard.edu
D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects
D000970:Antineoplastic Agents