Acute non-lymphocytic leukemia in patients with ovarian carcinoma following long-term treatment with Treosulfan (= dihydroxybusulfan).

Acute non-lymphocytic leukemia occurred in eight women following long-term treatment with Treosulfan (= dihydroxybusulfan) for ovarian carcinoma. The leukemia developed from 21 to 58 months (median 50 months) after the institution of chemotherapy. At the time when the leukemia appeared seven of the patients were in complete, and one in partial, remission as regards the ovarian carcinoma. Seven of the eight cases of acute leukemia occurred in a series of 553 patients treated with Treosulfan for ovarian cancer in the period from 1970 to 1977 and followed closely for a total of 1159 patient-years up to February 1978. As compared with an expected number of 0.04 cases of acute myeloblastic leukemia based on patient-years, the observed seven cases correspond to a 175-times increased risk. Although the cumulative probability of acute non-lymphocytic leukemia among surviving patients at five years using life-table statistics was 7.6%, the survival curve for the 553 patients with ovarian carcinoma was only slightly affected by death from leukemia. The probability of developing acute leukemia in this study was not significantly correlated to the total cumulative dosage of Treosulfan. Cytogenetic studies of the bone marrow performed after the development of acute leukemia showed chromosome abnormalities in all five patients examined, with hypodiploidy and loss of B and C group chromosomes.