Secondary myelodysplastic syndromes and leukemias

Although therapy-related (secondary) myelodysplastic syndromes and acute nonlymphocytic leukemias are most frequently observed following therapy of Hodgkin's disease and non-Hodgkin's lymphoma, the therapy of acute lymphocytic leukemia, multiple myeloma, polycythemia vera, cancers of breast, lung, ovary, gastrointestinal tract, testis, and soft tissues is also associated with subsequent development of leukemia. A preceding myelodysplastic syndrome is observed in over 70% of patients who develop therapy-related leukemia, in contrast to patients with de novo leukemia in whom approximately 20% of patients have similar prodromal syndromes. Chemotherapeutic drugs--including alkylating agents, platinum analogs, and epipodophyllotoxins--and ionizing radiation have both been implicated in the etiology of secondary tumors. The median duration from time of chemotherapy or radiation therapy, or both, to diagnosis of secondary leukemia is 3 to 4 years. The risk for development of secondary leukemia is highest between 24 and 72 months following cytotoxic therapy, with a steady decline in incidence thereafter. Of those people who will develop secondary leukemia, approximately 6% of patients do so within the 1st year, whereas 15% of patients will not do so until more than 7 years from commencement of mutagenic therapy. We review here selected recent publications on clinical and therapeutic data in therapy-induced myelodysplasia and acute leukemia.