TREATMENT OF RELAPSED OR REFRACTORY ACUTE-LEUKEMIA IN CHILDHOOD WITH BISANTRENE COMBINED WITH HIGH-DOSE ARACYTINE

Bisantrene is an anthracene derivative which has demonstrated activity in acute myeloblastic leukemia (AML) and in lymphoma. The present stu dy was designed to assess the reinduction rate and toxicity of bisantr ene (250 mg/m2/d x 5) associated with aracytine (1000 mg/M2 twice a da y x 5) in refractory and relapsed acute childhood leukemia. Patients w ho relapsed after bone marrow transplantation were eligible. Twenty-si x children were included. Diagnoses were as follows: 13 AML, 9 acute l ymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL). Al l patients had been very highly pretreated, especially with anthracycl ines, and most of them were of poor prognosis. The overall response ra te was 46% with a 95% confidence interval ranging from 27-65%. Accordi ng to diagnosis, complete remission (CR) rates are: AML: 5/13, ALL: 5/ 9, and AUL: 2/4. Four children died, three from infection and one from acute lysis syndrome. The major toxicity was infection with grade 3 a nd 4 episodes occurring in 42% of patients. No significant cardiac tox icity was noted. Hepatic and renal toxicity were limited and transient . Bisantrene in association with aracytine is effective in both AML an d ALL of childhood. Bisantrene should be evaluated with a five-day sch edule in other pediatric malignancies. In children with acute leukemia previously treated with high dose aracytine, new combination regimen is warranted. (C) 1994 Wiley-Liss, Inc.