Development of acute myeloid leukemia after chemotherapy for osteosarcoma.

The current study describes two patients with osteosarcoma who had acute myeloid leukemia develop after treatment with multiagent chemotherapy. The incidence density for the chemotherapy protocol was 129.8 per 10,000 person-year of followup. Karyotype analysis of 16 reported patients (including the current two patients) indicated that most leukemias after treatment of osteosarcoma correlated with the use of topoisomerase II inhibitors, such as doxorubicin. The deoxyribonucleic acid-damaging activity of doxorubicin reinforced by the use of alkylating agents is highly suspected as a causative event in the development of leukemia after treatment of osteosarcoma. As the next step in the development of treatment for patients with osteosarcoma, the type and intensity of treatment must be evaluated to minimize possible leukemogenic effects without compromising the potential for cure.