title: Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study.
abstract: OBJECTIVE
  To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.
  
  
  METHODS
  Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.
  
  
  RESULTS
  Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).
  
  
  CONCLUSIONS
  Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.
authors.affiliation: Department of Pediatrics, Division of Hematology and Oncology, National University Health System, Tower Block, 1E, Kent Ridge Rd, Singapore. allen_yeoh@nuhs.edu.sg
authors.forename: Allen Eng Juh
authors.initials: AE
authors.lastname: Yeoh
authors.forename: Hany
authors.initials: H
authors.lastname: Ariffin
authors.forename: Elaine Li Leng
authors.initials: EL
authors.lastname: Chai
authors.forename: Cecilia Sze Nga
authors.initials: CS
authors.lastname: Kwok
authors.forename: Yiong Huak
authors.initials: YH
authors.lastname: Chan
authors.forename: Kuperan
authors.initials: K
authors.lastname: Ponnudurai
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
authors.forename: Poh Lin
authors.initials: PL
authors.lastname: Tan
authors.forename: Mei Yoke
authors.initials: MY
authors.lastname: Chan
authors.forename: Shirley Kow Yin
authors.initials: SK
authors.lastname: Kham
authors.forename: Lee Ai
authors.initials: LA
authors.lastname: Chong
authors.forename: Ah Moy
authors.initials: AM
authors.lastname: Tan
authors.forename: Hai Peng
authors.initials: HP
authors.lastname: Lin
authors.forename: Thuan Chong
authors.initials: TC
authors.lastname: Quah
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008296:Malaysia; D008297:Male; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D011379:Prognosis; D012846:Singapore; D016896:Treatment Outcome