Acute myelogenous leukemia in patients receiving chlorambucil as long-term adjuvant chemotherapy for stage II breast cancer.

Thirteen consecutive stage II breast cancer patients were treated with long-term adjuvant chemotherapy using chlorambucil. At least three of these patients developed acute myelogenous leukemia (AML). All three patients (and possibly a fourth) who developed AML were postmenopausal, received continuous chlorambucil for greater than or equal to 4 years, had acute red cell anemia at the time of treatment, and had a wbc count in the range of 2700-7700/mm3. After the chlorambucil was discontinued, the wbc count began to slowly rise and the patient developed clinical AML. In all three patients, the diagnosis of AML was established by pathologists on the basis of bone marrow biopsy, aspirate, and peripheral smears. Each of these was subsequently reviewed by the hematologist who treated the patients for AML. Patients who have breast cancer (or any other solid tumor malignancy) are at risk to develop a second malignancy. However, an increasing number of reports are appearing suggesting more than just a casual relationship between leukemia and the use of alkylating agents. This may be related to the dose and duration of therapy with these agents.