Thiotepa for the treatment of thrombocythemia in patients with Philadelphia chromosome positive chronic myelogenous leukemia.

Abstract

Patients with chronic myelogenous leukemia (CML) occasionally experience persistent thrombocythemia despite having adequate white blood cell (WBC) counts. Trimethylenethiophosphoramide (thiotepa) is an alkylating agent that significantly inhibits platelet production. The authors studied the effects of thiotepa in eight patients with CML with persistent thrombocythemia. All patients had adequate WBC counts while receiving therapy for leukemia. The median age of the patients was 58 years, and all had received at least 2 prior therapy regimens for CML. Thiotepa was administered by intravenous infusion at a dose of 75 mg/m2 once every 2 to 3 weeks; doses were adjusted according to hematologic response. Seven patients were evaluable for response to thiotepa. Their pretreatment median platelet count was 1215 x 10(9)/L. After receiving the first dose, 6 patients (86%) had favorable responses as the median platelet count dropped to 348 x 10(9)/L (P = 0.02). However, all the patients' platelet counts returned to near baseline values after the first course. Patients required a median of three courses to achieve stable platelet counts near the normal range. In 4 patients (57%), administration of thiotepa was discontinued because of a stable normal platelet count after a median of 7.5 courses; 1 patient was still receiving treatment at last follow-up (18 courses) and 2 patients stopped receiving treatment after their disease progressed to the blastic phase. Toxicity was mostly hematologic, with neutropenia (< or = 1 x 10(9)/L) occurring during 5 of the 64 courses (8%) administered but only 1 patient's course was complicated by fever. The authors conclude that thiotepa is useful in controlling thrombocythemia in CML patients who have elevated platelet counts despite having adequate WBC counts.