Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukaemia

Authors

  • Nicholas J. Goulden,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
    2. Department of Paediatric Haematology, Royal Hospital for Sick Children, Bristol
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  • Christopher J. C. Knechtli,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
    2. Department of Paediatric Haematology, Royal Hospital for Sick Children, Bristol
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  • Russell J. Garland,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
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  • Kenneth Langlands,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
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  • Jeremy P. Hancock,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
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  • Michael N. Potter,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
    2. Department of Paediatric Haematology, Royal Hospital for Sick Children, Bristol
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  • Colin G. Steward,

    1. Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol,
    2. Department of Paediatric Haematology, Royal Hospital for Sick Children, Bristol
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  • Anthony Oakhill

    1. Department of Paediatric Haematology, Royal Hospital for Sick Children, Bristol
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Dr Colin G. Steward Oncology Day Beds, Royal Hospital for Sick Children, St Michael’s Hill, Bristol BS2 8BJ.

Abstract

We report a largely retrospective analysis of minimal residual disease (MRD) in a cohort of 66 children suffering from acute lymphoblastic leukaemia (ALL). All patients lacked high-risk features at diagnosis, i.e. the presenting white cell count was <50 × 109/l, age 1–16 years and translocations t(9;22) and t(4;11) were not present. All were treated according to either the MRC protocols UKALL X or XI. PCR of IgH, TCRδ and TCRγ gene rearrangements and allele-specific oligoprobing were employed for the detection of MRD. Sensitivity was at least 10−4 in 78/82 (93%) probes examined.

A total of 33 patients relapsed (seven on therapy and 26 off) and 33 remain in continuing complete remission (CCR) (median follow-up 69 months from diagnosis). Of those who remain in CCR, MRD was present in the bone marrow in 32%, 10% and 0% at 1, 3 and 5 months into therapy respectively. This is in marked contrast to the presence of MRD at these times in 82%, 60% and 41% of patients who relapsed (P<0.001, P<0.005 and P<0.005). These results provide further evidence of a strong correlation between clearance of MRD early in therapy and clinical outcome in childhood ALL.

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