Randomised Introduction of 2-CDA as Intensification during Consolidation for Children with High-risk AML - Results from Study AML-BFM 2004
Abstract
Background: The outcome in children and adolescents with high-risk (HR) acute myeloid leukemia (AML) is still unsatisfactory. Therefore, in study AML-BFM 2004 we aimed to improve outcome of HR-patients by adding moderately dosed 2-Chloro-2-Deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without increasing toxicity.
The aim was to improve prognosis especially in FAB M4/M5/MLL patients, who represent the largest subgroup of HR patients. Patients and Methods: In total, 343 children and adolescents with HR-AML were randomized to receive or not 2-CDA (6 mg/m(2)/d, days 1, 3) in combination with cytarabine/idarubicine (AI = 500 mg/m(2) cytarabine 5 days continuous infusion plus 7 mg/m(2)/d idarubicin, days 3 and 5).
Results: Results for patients of the AI/2-CDA arm (n = 168) vs. the AI-arm (n = 175) were similar: 5-year overall survival 68 +/- 4 vs. 72 +/- 4 %, p(logrank) = 0.38, event-free survival 53 +/- 4 vs. 49 +/- 4 %, p(logrank) = 0.77; cumulative incidence of relapse at 5 years: 35 +/- 4 vs. 37 +/- 4 %, p((Gray)) = 0.89. Results in patients with MLL rearrangement or FAB M4/M5 were also similar in the treatment groups.
In addition, toxicities did not differ between the two arms. Conclusion: We conclude that additional, moderate dose 2-CDA does not improve prognosis in HR-patients when given during consolidation treatment.
Its effect might be too low in this multidrug regimen, where the strongest effects are achieved during induction, or the chosen dose of 2-CDA might have been too low.