Forty-four patients with a diagnosis of refractory or relapsed acute myelogenous leukemia received salvage chemotherapy with high-dose cytosine arabinosine 3 g/m2 intravenously over 2 hours every 12 hours for six doses and mitoxantrone 5 mg/m2 intravenously daily for 5 days. Overall 16 patients (36%) had a complete remission; 16 patients (36%) had resistant disease; and 12 (27%) died during induction therapy. The most significant predictive factor for remission was the duration of first remission: the response rate was 17% for patients whose first remission duration was shorter than 12 months (including those who did not achieve a first remission), 45% for those with a first remission lasting between 12 to 18 months, and 69% for those with longer remission durations (P = 0.008). Other predictive factors for higher response rates were a younger age group, a good performance status, and a favorable or diploid karyotype. The median survival from start of therapy was 4 months for the total population and 10 months for patients with remission. Serious side effects including pulmonary toxicity and neurotoxicity occurred in less than 10% of patients. This incidence was significantly lower than previous high-dose cytosine arabinoside schedules of 3 g/m2 for nine to 12 doses (total dose, 27 to 36 g per course). Significant granulocytopenia and thrombocytopenia were universal resulting in fever or documented infections in 98% of patients. We conclude that the combination of high-dose cytosine arabinoside and mitoxantrone is an effective antileukemic regimen with acceptable toxicity. Future studies should incorporate it as part of the frontline induction or maintenance strategies in newly diagnosed patients with acute myelogenous leukemia.
Cancer 62677482,1988.
ESPITE SIGNIFICANT PROGRESS in the therapy of D acute myelogenous leukemia (AML) about 70% of patients who have a complete remission (CR) with induction therapy will eventually relapse. The prognosis of patients with AML who relapse is ominous. The remission rates are less than 30% in first salvage and less than 10% in subsequent salvage^.^,^ The long-term survival rate in AML is less than 5% after r e l a p ~e , ~-~ stressing the need to identify new active agents or regimens to improve patient outcome.
Recently, encouraging results were reported in several Phase I1 studies using high doses of cytosine arabinoside (high-dose ara-C)6-9 and of mito~antrone.'~-'~ The most active antileukemic agent, Ara-C, produced remission rates of 25% to 80% when used in a high-dose intermit-From the Department of Hematology, M.