Key result
Addition of anthracyclines to standard therapy in childhood ALL did not significantly increase event-free survival at 5 years (56.7% vs 52.8%; OR 0.91; 95% CI 0.76-1.10; P=0.3).
Why the study?
Does the addition of anthracyclines improve event-free survival or affect cardiotoxicity in childhood acute lymphoblastic leukaemia?
Meta-Analysis (n=958)
Does the addition of anthracyclines improve event-free survival or affect cardiotoxicity in childhood acute lymphoblastic leukaemia?
In childhood ALL, adding anthracyclines reduces bone marrow relapse but does not significantly improve 5-year event-free survival, with insufficient data to definitively assess cardiotoxicity.
Answers are grounded in this paper and cite their sources.
No EFS benefit from adding anthracyclines in childhood ALL; challenges routine use and leaves cardiotoxicity impact unresolved.
Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta-analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non-significantly, non-bone marrow relapse, resulting in an increased relapse-free interval. However there was a non-significant increase in induction failures, and in deaths in first remission. Event-free survival at 5 years was 56.7% with anthracycline versus 52.8% without (Odds Ratio = 0.91; 95% Confidence Interval = 0.76-1.10; P = 0.3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.
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Childhood Acute Lymphoblastic Leukaemia Collaborative Group (2009) conducted a meta-analysis in Childhood acute lymphoblastic leukaemia (ALL) (n=958). Anthracyclines vs. Standard therapy without anthracyclines was evaluated on Event-free survival at 5 years (OR 0.91, 95% CI 0.76-1.10, p=0.3). Addition of anthracyclines to standard therapy in childhood ALL did not significantly increase event-free survival at 5 years (56.7% vs 52.8%; OR 0.91; 95% CI 0.76-1.10; P=0.3).
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