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Definition of a standard-risk group in children with AML
U Creutzig1, M Zimmermann, J Ritter
1University Children's Hospital, Münster, Germany. ucreutzig@aol.com
Insights
This study identified favorable prognostic factors for pediatric acute myeloid leukemia (AML) in children under 17. Combining bone marrow blast counts and morphology can define a standard-risk group for tailored therapy.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Research
Background:
- Acute myeloid leukemia (AML) in children requires risk stratification for effective therapy.
- Previous studies have identified various prognostic factors, but a clear definition for a standard-risk group in pediatric AML is needed.
Purpose of the Study:
- To define pediatric AML patients with a favorable outcome.
- To establish criteria for a standard-risk group to design risk-adapted therapy.
Main Methods:
- Analysis of 489 children under 17 treated in AML-BFM 83 and 87 studies.
- Multivariate analysis to identify prognostic factors including bone marrow blasts on day 15, morphology, and hyperleucocytosis.
- Kaplan-Meier survival analysis.
Main Results:
- 5-year survival, event-free survival (EFS), and disease-free survival (DFS) were 50%, 43%, and 58%, respectively.
- Day 15 blast count (< or = 5% vs >5%) and favorable morphology (M1/M2 with Auer rods, M3, M4eo) were significant prognostic indicators.
- Hyperleucocytosis was an independent high-risk factor. Specific karyotypes (t(8;21), t(15;17), inv16) correlated with favorable morphology and outcomes.
Conclusions:
- A combination of morphological criteria and early response (day 15 blast reduction) is sufficient to define a standard-risk group in pediatric AML.
- This standard-risk group, comprising 31% of patients, demonstrated significantly improved 5-year survival (73%), EFS (68%), and DFS (76%).
Abstract:
To define paediatric AML patients with a favourable outcome in order to design a risk-adapted therapy, we analysed 489 children under 17 years of age treated similarly in studies AML-BFM 83 and 87. 369 patients (75.4%) achieved remission. Estimated probabilities of survival, event-free survival (EFS) and disease-free survival (DFS) at 5 years were 50% (SE 2%), 43% (SE 2%) and 58% (SE 3%), respectively. Multivariate analysis revealed bone marrow blasts on day 15, morphologically defined risk groups and hyperleucocytosis to be of prognostic value. EFS at 5 years estimated for patients with < or = 5% and >5% blasts on day 15 were 56% (SE 3%) v 27% (SE 4%); for the favourable morphological subgroups (M1/M2 with Auer rods, M3 and M4eo) it was 60% (SE 4%) compared with other patients (33%, SE 3%), P (Kaplan-Meier) = 0.0001 each. Hyperleucocytosis proved to be an independent prognostic factor, indicating a high risk, especially for early failure. The specific karyotypes t(8;21), t(15;17) and inv16 were closely related to the favourable morphology and outcome was in the same range. We conclude that for the definition of a standard-risk group a combination of morphological and response criteria may be sufficient. The standard-risk group defined by favourable morphology and a blast cell reduction on day 15 (not required for M3) comprises 31% of all patients, P survival, pEFS and pDFS at 5 years were 73% (SE 4%), 68% (SE 5%) and 76% (SE 4%), respectively.