Polymerase chain reaction (PCR)- and reverse transcription PCR-based minimal residual disease detection in long-term follow-up of childhood acute lymphoblastic leukaemia.

Minimal residual disease (MRD) was investigated in 52 children with acute lymphoblastic leukaemia (ALL), using antigen receptor gene rearrangements and reverse transcription polymerase chain reaction for fusion transcripts as molecular targets. Patients [treated according to the Medical Research Council United Kingdom ALL (MRC UKALL) XI protocol or Total XI and XIII protocols] were monitored for a median period of 45 months (range, 9-110 months). Among 17 patients who relapsed, MRD persisted for longer (66.7%, 47.1%, 53.8% and 41.7% at 0-2, 3-5, 6-9, 10-24 months respectively) than patients who remained in continuous clinical and immunological remission (n = 35) (27.3%, 11.1%, 4.3%, 8.0%). Association between MRD tests and outcome was assessed and found to be significant at all time-points. The difference in survival for MRD-positive and MRD-negative patients (using the log-rank test) was statistically significant at all time intervals, as was risk of relapse for MRD-positive patients (1.89, 2.20, 2.65 and 2.16) and MRD-negative patients (0.72, 0.82, 0.65 and 0.70). Sixteen of the 52 patients had an oligoclonal pattern at presentation but oligoclonality did not have an impact on outcome. Cox regression analysis revealed that MRD assessment is an independent and prognostically significant factor during treatment and should be used for patients' stratification in future studies.