Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93

Abstract

In the randomized trial AML-BFM 93 we compared 60 mg/m 2 /day daunorubicin with 12 mg/m 2 /day idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of patients with у5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, P 2 = 0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19% vs 38%, P 2 = 0.007). Cardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils Ͼ500/ l of 25 days (daunorubicin) compared to 27 days (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin (49% ± 4% vs 55% ± 4% and 57% ± 4% vs 64% ± 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity. Leukemia (2001) 15, 348-354.

Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols

“…The comparable CR rate of our studies is in agreement with previously published reports documenting that substitution of daunorubicin with idarubicin, despite favouring blast clearance on day 15, does not substantially improve the CR rate. 19 Also, Table 5 Results according to different risk parameters in studies AIEOP LAM 82, 87, 87M and 92 (only patients o15 years at diagnosis): 5-year probability of EFS (%), only for subgroups nX10 20,21 The main change in the overall treatment strategy of the four consecutive AIEOP studies regarded postremissional treatment. In fact, in the first study, patients were given repeated courses of mild-intensity chemotherapy, only a minority of children receiving ALLO_SCT in first CR.…”

Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador

“…Between January 2000 and December 2006, patients with AML were treated according to the AHOPCA-AML 1999 protocol, which was based on BFM-AML93 (Creutzig et al, 2001). Significant modifications included the treatment of all children as low risk (without stem cell transplantation, which is unavailable in the region), reduction of daunorubicin by 66%, omission of etoposide during induction and intensification, omission of cyclophosphamide during consolidation, use of high-dose cytarabine and mitoxantrone only in patients without response after induction plus consolidation, and reduction of maintenance therapy to 12 months.…”

Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93

“…7 Briefly, the patients were randomized at diagnosis to receive the 8-day induction with either daunorubicin (ADE: cytarabine 100 mg/m 2 /day continuous infusion on days 1 and 2 followed by a 30 min infusion every 12 h on days 3-8, daunorubicin 30 mg/m 2 every 12 h on days 3-5 and etoposide (VP-16) 150 mg/m 2 on days 6-8) or with idarubicin (AIE: idarubicin 12 mg/m 2 every 24 h, days 3-5 instead of daunorubicin, cytarabine, and VP-16 as in ADE). After induction, patients were treated according to risk groups.…”