Toxicity and effectivity of high-dose idarubicin during AML induction therapy:: Results of a pilot study in children

Background: Idarubicin (IDR) is one of the most effective, but also toxic drugs in the treatment of AML. The standard dose used in children and adults is 8-12 mg/m(2) during induction. Patients and methods: To improve outcome, we increased the IDR dose from 12 mg/m(2) (standard dose in study AML-BFM 93), applied over three days during induction therapy (AIE = Ara-C, Idarubicin, Etoposide) to 14 mg/m(2) in a pilot study including 17 patients (16 with de novo AML, one with secondary AML). Outcome and toxicities were compared with the other patients of study AML-BFM 93, treated with 3 x 12 mg/m(2) IDR or 6 x 30 mg/m(2) daunorubicin (DNR). Results: Patients of the pilot study achieved a good blast cell reduction in the bone marrow on day 15, a high CR rate of 94% and a low relapse rate (3/17 pts.), however, not significantly different to the IDR (12 mg/m(2)) group. Hematological toxicity was high, median duration until neutrophil recovery >500/mu l was 25.0 (12-66) days, and similar to the IDR (12 mg/m(2)) and DNR groups. Duration of thrombocytopenia (time to > 20 000/mu l ) was 21 (10-66) days in the pilot study compared to 19 (7-26) days in DNR patients (p = 0.08). four of 17 pilot patients presented with severe WHO grades 3/4 of mucositis during induction. One patient died in long-lasting aplasia after the 3rd treatment block. Conclusion: Results of this pilot study show that the IDR 14 mg/m(2) regimen was effective but also toxic. According to our results which, however, are based on small patient numbers, an improved outcome compared to the IDR 12 mg/m(2) regimen seems to be unlikely, therefore the possibly increased toxicity might not be acceptable.