title: Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study.
abstract: The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if ≥ 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD ≥ 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP.
authors: Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. schrappe-office@pediatrics.uni-kiel.de
authors: Martin
authors: M
authors: Schrappe
authors: Maria Grazia
authors: MG
authors: Valsecchi
authors: Claus R
authors: CR
authors: Bartram
authors: André
authors: A
authors: Schrauder
authors: Renate
authors: R
authors: Panzer-Grümayer
authors: Anja
authors: A
authors: Möricke
authors: Rosanna
authors: R
authors: Parasole
authors: Martin
authors: M
authors: Zimmermann
authors: Michael
authors: M
authors: Dworzak
authors: Barbara
authors: B
authors: Buldini
authors: Alfred
authors: A
authors: Reiter
authors: Giuseppe
authors: G
authors: Basso
authors: Thomas
authors: T
authors: Klingebiel
authors: Chiara
authors: C
authors: Messina
authors: Richard
authors: R
authors: Ratei
authors: Giovanni
authors: G
authors: Cazzaniga
authors: Rolf
authors: R
authors: Koehler
authors: Franco
authors: F
authors: Locatelli
authors: Beat W
authors: BW
authors: Schäfer
authors: Maurizio
authors: M
authors: Aricò
authors: Karl
authors: K
authors: Welte
authors: Jacques J M
authors: JJ
authors: van Dongen
authors: Helmut
authors: H
authors: Gadner
authors: Andrea
authors: A
authors: Biondi
authors: Valentino
authors: V
authors: Conter
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors