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Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials

Leukemia volume 19, pages 2130–2138 (2005)Cite this article

Abstract

Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy.

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Acknowledgements

The MRC/UK Childhood Leukaemia Working Party acknowledge the very significant contribution to MRC AML 10 and subsequent trials of Dr Richard Stevens (Deceased). For Acknowledgements refer to Supplementary Information.

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Authors and Affiliations

  1. Royal Hospital for Sick Children, Glasgow, UK

    B E S Gibson

  2. Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK

    K Wheatley & R K Hills

  3. Great Ormond Street Hospital for Children, London, UK

    I M Hann & D Webb

  4. Royal Manchester Children's Hospital, Manchester, UK

    R F Stevens

  5. Dutch Childhood Oncology Group, The Hague, The Netherlands

    S S N De Graaf

  6. Cancer Sciences Division, LRF Cytogenetic Group, University of Southampton, Southampton, UK

    C J Harrison

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  1. B E S Gibson
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  2. K Wheatley
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  7. S S N De Graaf
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for the United Kingdom Childhood Leukaemia Working Party, and the Dutch Childhood Oncology Group

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Correspondence to B E S Gibson.

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Supplementary Information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Gibson, B., Wheatley, K., Hann, I. et al. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia 19, 2130–2138 (2005). https://doi.org/10.1038/sj.leu.2403924

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  • DOI: https://doi.org/10.1038/sj.leu.2403924

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