Two Subtypes of Therapy-Related Leukemia; Experience from The Copenhagen Series

Abstract

For more than 20 years the many aspects of t-MDS and t-AML, including risk factors incidence and chromosome characteristics: have been evaluated in numerous studies, as reviewed extensively elsewhere [1–7]. The risk has primarily been related to previous therapy with the alkylating agents, but more recently also to therapy with the epipodophyllotoxins. In a few studies high voltage radiotherapy has been shown to play a minor role, in other studies it was not a significant risk factor. Risk estimates have shown great variation from study to study, probably due to differences in patient age and treatment intensity. In addition variation in ascertainment of cases may also have played a role, as cases of t-MDS may easily have been overlooked in studies where cytogenetic screening was not performed in all patients developing refractory, unexplained cytopenia. Since the first report in 1977 [8], however, a more consistent finding in t-MDS and t-AML after therapy with alkylating agents has been the loss of whole chromosomes no. 5 or no. 7, or of various parts of the long arm of these two chromosomes. Recently, rearrangements of the long arm of chromosome no. 11 were reported as characteristic of leukemias following therapy with the epipodophyllotoxins [9,10]. Subsequently, specific balanced translocations involving bands 11q23 and 21q22 were shown to be significantly associated not only with previous therapy with the epipodophyllotoxins but also with other cytostatic drugs targeting at DNA-topoisomerase II such as the anthracyclines [11,12].