EFFICACY AND SAFETY OF MITOXANTRONE AND ETOPOSIDE (ME) IN REFRACTORY AND RELAPSED ACUTE NONLYMPHOCYTIC LEUKEMIA

Mitoxantrone and etoposide (ME) both have been shown to be active in m onotherapy trials of relapsed and refractory acute nonlymphocytic leuk emia (ANLL). Ln the present study 17 children (mean age 6.5 years; ran ge 18 months to 14 years) with ANLL were treated with these agents. To xicity and antileukemic activity were assessed. In 7 patients, ANLL wa s primarily refractory to conventional treatment, 6 patients had relap ses while receiving therapy after an initial complete remission had be en achieved, and four patients had relapses while not receiving therap y. The first 5 patients received mitoxantrone (10 mg/m(2)) and etoposi de (100 mg/m(2)) daily for 3 days (ME-3). The subsequent 12 received t he same therapy for 5 days (ME-5). Responses after one course of thera py were as follows: complete remission in 10 of 17 patients (59%), par tial remission in 4 of 17 patients (23%) and no response in 3 of 17 pa tients (18%). Severe myelosuppresion with absolute granulocyte count < 0.5 x 10(9)/L and platelet count <10 x 10(9)/L was observed in 16 pati ents with a median duration of 18 days (range, 10 to 35 days). All pat ients became febrile during neutropenia. Infectious complications incl uded bacteremia (3 patients), soft tissue infection (6 patients), cath eter-related infections (2 patients) and pneumonia (1 patient). Severe mucositis was observed in 10 of 17 patients (59%). Drug-related cardi ac events were not observed, but in 1 patient decreased left ventricul ar ejection fraction was found. Central nervous system, renal and hepa tic toxicities were not observed. In general, toxicity was milder with the ME-3 regimen, whereas the complete response rate was better with the ME-5 regimen (67% versus 40%), but the final outcome did not diffe r if a 3- or 5-day regimen was used. In summary, the combination of mi toxantrone and etoposide is effective salvage treatment for refractory and relapsed ANLL with acceptable toxicity. Duration of response, how ever, is short even when bone marrow transplantation was used as conso lidation therapy.