Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy

Therapy-related MDS and AML are complications of intensive chemotherapy reg imens. Traditionally, patients exposed to topoisomerase II inhibitors are r eported to develop secondary AML with abnormalities of chromosome 11q23. We evaluated the long-term hematologic toxicity of topoisomerase II-intensive high-dose mitoxantrone-based chemotherapy in 163 newly diagnosed acute leu kemia patients treated over an 8 year period. Nine (5.5%) patients develope d new cytogenetic abnormalities. Four patients developed MDS with progressi on to AML, three patients developed new abnormalities at the time of relaps e, and three patients (including one of the former patients) had changes th at were not associated with hematologic disease. The abnormalities most fre quently involved chromosomes 7q, 20q, 1q, and 13q. Despite the use of topoi somerase Ii-intensive treatment, no patient developed an abnormality involv ing chromosome 11q23. Spontaneous resolution of some changes and prolonged persistence of others in the absence of hematologic disease indicates that some cytogenetic changes are not sufficient to promote leukemogenesis.