Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukaemia.
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.
Goulden
N J
NJ
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, and Royal Hospital for Sick Children.
Knechtli
C J
CJ
Garland
R J
RJ
Langlands
K
K
Hancock
J P
JP
Potter
M N
MN
Steward
C G
CG
Oakhill
A
A
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