title: Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL.
abstract: 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 MRD-based 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 relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk 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.
authors.affiliation: Department of Immunology, University Hospital Rotterdam/Erasmus University Rotterdam, The Netherlands.
authors.forename: Marja J
authors.initials: MJ
authors.lastname: Willemse
authors.forename: Taku
authors.initials: T
authors.lastname: Seriu
authors.forename: Klaudia
authors.initials: K
authors.lastname: Hettinger
authors.forename: Elisabetta
authors.initials: E
authors.lastname: d'Aniello
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: E Renate
authors.initials: ER
authors.lastname: Panzer-Grümayer
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Willem A
authors.initials: WA
authors.lastname: Kamps
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Masera
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Hansjoerg
authors.initials: H
authors.lastname: Riehm
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement / Q000235:genetics; D019672:Genes, T-Cell Receptor / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007945:Leukemia, Lymphoid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011241:Prednisone