THERAPY-RELATED MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA: ETIOLOGY, PROGNOSIS AND TREATMENT

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a group of heterogeneous disorders characterized by abnormal hematopoiesis of myeloid cells, uni- or multilineage peripheral cytopenia, marrow dysplasia and cytogenetic abnormalities. Collectively, these disorders are referred to as myeloid neoplasms. When AML or MDS results from prior therapy, usually chemotherapy or radiation, it is referred to as therapy-related MDS/AML, or more generally, the myeloid neoplasms. Treatments for therapy-related myeloid neoplasms are often ineffective and the prognosis is poor, as evidenced by a median survival of 6-12 months after diagnosis. A number of causative agents, including alkylating agents and topoisomerase inhibitors, are discussed, along with common primary malignancies, the treatment of which increases the risk of developing therapy-related myeloid neoplasms. Investigation of the molecular basis of therapy-related myeloid neoplasms has revealed numerous polymorphisms and cytogenetic abnormalities that are associated with the development and prognosis of these neoplasms. An overview of these polymorphisms and cytogenetic abnormalities is provided, along with current therapeutic strategies.