Mitoxantrone and high-dose cytosine arabinoside for the treatment of refractory acute lymphocytic leukemia

Although great advances in the treatment of acute lymphocytic leukemia (ALL) have been made over the past two decades, its prognosis still depends strongly on several host and tumor attributes. Characteristics like patient age, degree of leukocytosis, and chromosome abnormalities of the tumor cells all influence the relative chances for long-term remission, which range from 40 to 50 percent in patients at average risk and less than 20 percent for patients with greater risk factors. Refractory ALL, which doesn't respond to conventional treatment, has been treated with high doses of cytosine arabinoside (ara-C), and response rates of between 20 and 60 percent have been reported. Likewise, mitoxantrone has been used in these patients and similar response rates have been found. Since the toxic effects of ara-C and mitoxantrone do not overlap, there is little reason not to try both drugs simultaneously, and there may, in fact, be some beneficial antileukemic effects as a result of combining them. To examine this combination of drugs, 25 patients with a diagnosis of refractory ALL were treated with 5mg per square meter (of body surface) mitoxantrone over one hour daily for five days, and 3mg ara-C over two hours every twelve hours for six doses. For purposes of this study, complete remission was defined on the basis of bone marrow examination. A percentage of blast cells, immature, undifferentiated cells, under 5 percent was regarded as complete remission (CR). Complete remission was observed in 9 of 25 patients (36 percent). Eight patients had disease which was resistant to this treatment, and another eight died during the treatment, primarily of complications induced by chemotherapy. The overall median survival time for the 25 patients was 10 weeks, while among the patients achieving remission, the median survival period was 16 weeks. Although the improvement in survival seems promising, the deaths due to the suppression of the bone marrow were higher than seen with some other treatments, suggesting that some sort of additional support for immune function be provided patients treated with mitoxantrone and high-dose cytosine arabinoside. (Consumer Summary produced by Reliance Medical Information, Inc.)