title: Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukaemia.
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 x 10(9)/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, TCRdelta and TCRgamma 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.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, and Royal Hospital for Sick Children.
authors.forename: N J
authors.initials: NJ
authors.lastname: Goulden
authors.forename: C J
authors.initials: CJ
authors.lastname: Knechtli
authors.forename: R J
authors.initials: RJ
authors.lastname: Garland
authors.forename: K
authors.initials: K
authors.lastname: Langlands
authors.forename: J P
authors.initials: JP
authors.lastname: Hancock
authors.forename: M N
authors.initials: MN
authors.lastname: Potter
authors.forename: C G
authors.initials: CG
authors.lastname: Steward
authors.forename: A
authors.initials: A
authors.lastname: Oakhill
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005544:Forecasting; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity