Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome

Abstract

The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day 15 (D15) and day 29 (D29) after the start of induction therapy (rs = 0.70, P < .0001). The 15 patients with T-cell disease had higher D29 MRD than those with B-lineage ALL (P = .01). Age was positively related to D29 MRD (rs = 0.32, P = .001). The 16 patients who had a relapse had higher D15 and D29 MRD levels than the patients who stayed in remission (median levels D15, 1% versus 0.1%,P = .03; D29, 0.4% versus 0.01%,P = .0001). No patients with a MRD level less than 0.01% on D29 have so far had a relapse, whereas the 7-year probability of event-free survival for patients with higher MRD levels was 0.52 (P = .0007). The group of patients with a D29 MRD less than 0.01% included patients with T-cell disease, white blood cell count more than 50 × 109/L at diagnosis, or age 10 years or older, and could not be identified by up-front criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD (P = .004) and age (P = .009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a very low risk of relapse. Further trials are needed to reveal whether such patients with D29 MRD less than 0.01% can be cured with less intensive chemotherapy, which would reduce the risk of serious late effects as well as the costs of therapy.