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Improved outcome in childhood acute myeloid leukemia in Singapore with the MRC AML 10 protocol
Ronald M Tan1, Thuan Chong Quah, Lele Aung
1Division of Pediatric Hematology-Oncology, The Children's Medical Institute, National University Hospital, National University of Singapore, Singapore.
Insights
The United Kingdom Medical Research Council
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- The United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol, incorporating high-dose anthracycline therapy, has improved outcomes for children with acute myeloid leukemia (AML).
- This study reviews childhood AML therapy outcomes and toxicity over 17 years at a Singapore university hospital.
Purpose of the Study:
- To evaluate the effectiveness and toxicity of the MRC AML 10 protocol in a Singaporean pediatric AML cohort.
- To compare outcomes between children treated with the MRC AML 10 protocol and those treated with previous regimens.
Main Methods:
- Retrospective analysis of 34 children diagnosed with AML between 1988 and 2003.
- Comparison of outcomes for patients treated before and after September 1996, when the MRC AML 10 protocol was implemented.
Main Results:
- Patients treated with the MRC AML 10 protocol showed significantly better 3-year overall survival (74% vs. 35%), event-free survival (77% vs. 20%), and disease-free survival (83% vs. 31%).
- MRC AML 10-treated patients were more likely to achieve complete remission (CR), with a higher proportion achieving CR after a single chemotherapy cycle.
- Hematologic toxicity was comparable across different treatment regimens.
Conclusions:
- The MRC AML 10 treatment significantly improves survival in pediatric acute myeloid leukemia without increasing toxicity.
- Further research is needed to identify key components of the MRC AML 10 protocol and optimize anthracycline dosage to maintain efficacy.
Background:
The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome.
Procedure:
Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment.
Results:
At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9).
Conclusions:
These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome.