Twenty-seven patients with essential thrombocythemia were treated with combination chemotherapy consisting of weekly intravenous thiotepa (until the platelet count fell below 1,000 X 10(3)/cu mm) and daily chlorambucil (until a sustained remission, platelet count less than 400 X 10(3)/cu mm). All patients responded promptly, platelet counts fell to below 1,000 X 10(3)/cu mm by 1–3 wk, and were less than 400 X 10(3)/cu mm by 2–6 wk. Remission of thrombocytosis was accompanied by an improvement of the patients' symptoms and resolution of the splenomegaly that was present in 21 of the 27 patients. However, daily chlorambucil for more than 1 yr was required to produce a sustained remission in the majority of patients. Nine of 21 patients whose initial treatment was discontinued have required retreatment. To date, 3 patients have expired; 1 patient developed acute leukemia at 36 mo.

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