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Blood. 2002 Feb 15;99(4):1253-8.

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

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  • 1Department of Clinical Immunology and Department of Pediatrics, National University Hospital, Rigshospitalet, Copenhagen, Denmark.


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 (r(s) = 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 (r(s) = 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 x 10(9)/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.

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