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We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n ‫؍‬ 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10 ؊3 or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n ‫؍‬ 43) over the MRDbased risk groups differed significantly from that of precursor B-ALL (n ‫؍‬ 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P ‫؍‬ .01) and had a 5-year relapsefree survival (RFS) rate of 98% or greater.In contrast, 28% of patients with T-ALL were classified in the MRD-based highrisk group compared to only 11% of patients with precursor B-ALL (P ‫؍‬ .02), and the RFS rates were 0% and 25%, respectively (P ‫؍‬ .03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points. IntroductionChildhood acute lymphoblastic leukemia (ALL) has a B-lineage origin in approximately 85% of patients and a T-lineage origin in the remaining approximately 15% of patients. 1 Typical T-lineage ALL (T-ALL) is diagnosed in male adolescents and is frequently characterized by hyperleukocytosis, mediastinal mass, and central nervous system involvement. 2,3 Children with T-ALL generally have a poorer prognosis than those with precursor B-lineage ALL (B-ALL). 1,4 In T-ALL, the following characteristics were shown to have a negative effect on treatment outcome: patient age 15 years or older, L2 blast morphology, karyotype other than hyperdiploidy, and CD3 ϩ . 2,3 The most immature T-ALLs (CD1 Ϫ / CD3 Ϫ ) are also associated with unfavorable outcome, whereas CD1 ϩ T-ALL forms a distinct subgroup with an excellent prognosis on intensive high-risk treatment. [4][5][6][7] Early in vivo response has been identified as one of the strongest prognostic factors in childhood ALL. [8][9][10][11][12] Patients with T-ALL frequently have a poor in vivo steroid response 9,12,13 and are resistant to many drugs, as demonstrated by in vitro assays. 14 Nevertheless, treatment outcome has significantly improved, and the sustained relapse-free s...

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