Journal of Clinical Oncology, Vol 16, 3616-3627, Copyright © 1998 by American Society of Clinical Oncology
Residual disease detection using fluorescent polymerase chain reaction at 20 weeks of therapy predicts clinical outcome in childhood acute lymphoblastic leukemia
PA Evans, MA Short, RG Owen, AS Jack, PD Forsyth, CR Shiach, S Kinsey and GJ Morgan
Department of Haematology, The General Infirmary at Leeds, United Kingdom.
PURPOSE: Ninety-five percent of children with acute lymphoblastic leukemia
(ALL) will achieve a remission, but approximately 25% will relapse.
Identifying these patients is difficult, as patients with adverse
prognostic features at presentation are rare and the majority are standard
risk. Analysis of minimal residual disease (MRD) may be able to determine
those at risk of relapse, but the best method by which this can be
accomplished has yet to be defined. The object of this study was to
determine the predictive value of residual disease detection in a group of
standard-risk patients with precursor-B ALL at a fixed point in therapy
(week 20) using a simple fluorescent consensus immunoglobulin H (IgH) heavy
chain polymerase chain reaction (PCR). PATIENTS AND METHODS: Forty-two
patients who presented with precursor-B ALL with standard-risk clinical
features and treated according to either the Medical Research Council (MRC)
UKALL X or XI protocols were assessed using a combination of both
fluorescent consensus framework I and framework III Ig heavy-chain PCR. The
results of the PCR were analyzed on an ABI 373 gene sequencer with genescan
software (Applied Biosystems, Foster City, CA). Clonal rearrangements
detected at presentation were looked for at week 20. RESULTS: Of 42
patients, 35 had a clonal population detectable at presentation; of these,
seven had more than two clonal rearrangements; this latter group showed a
similar disease-free survival (DFS) to the group as a whole. Thirty of 35
patients were analyzed before their second course of intensification
therapy at week 20. At this point, nine of 30 had a detectable clonal
rearrangement, eight (89%) of whom have since relapsed with a median DFS of
27.5 months. Of the rest of the group (n=21), in whom no clonal
rearrangement was detectable, only six (21%) have relapsed. CONCLUSION:
Fluorescent IgH PCR at week 20 provides a sensitive and specific means to
predict ultimate relapse (57% and 89%, respectively) and is a simple yet
promising technique for the identification of patients at risk of poor
outcome.
