High risk of therapy-related leukemia and preleukemia after therapy with prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen for advanced breast cancer

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Abstract
Therapy-related acute non-lymphocytic leukemia or preleukemia was observed in five of 71 patients with advanced breast cancer treated with combination chemotherapy comprising prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen. In this closely followed cohort of patients the cumulative risk of leukemic complications was 25.4% ± 10.3% (± SE) 37 months after start of chemotherapy. The relative risk of overt leukemia was 339 (95% CI: 41-1223), as two cases were observed versus 0.0059 cases expected. The very high risk of leukemia and preleukemia observed may partly reflect the advanced age of the patients (mean, 61 years) and partly the diagnostic procedures used, which included cytogenetic screening of all patients developing refractory cytopenia. A particularly high leukemogenic effect of prednimustine or a synergism between prednimustine and other drugs used in this study cannot be excluded. In the light of the above results, the authors caution against the use of intensive combination chemotherapy with alkylating agents as in the current study in potentially curable patients with breast cancer.