title: Importance of minimal residual disease testing during the second year of therapy for children with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  A high level of minimal residual disease (MRD) after induction chemotherapy in children with acute lymphoblastic leukemia (ALL) is an indicator of relative chemotherapy resistance and a risk factor for relapse. However, the significance of MRD in the second year of therapy is unclear. Moreover, it is unknown whether treatment intervention can alter outcome in patients with detectable MRD.
  
  
  METHODS
  We assessed the prognostic value of MRD testing in bone marrow samples from 85 children at 1, 12, and 24 months from diagnosis using clone-specific polymerase chain reaction primers designed to detect clonal antigen receptor gene rearrangements. These children were part of a multicenter, randomized clinical trial, which, in the second year of treatment, compared a 2-month reinduction-reintensification followed by maintenance chemotherapy with standard maintenance chemotherapy alone.
  
  
  RESULTS
  MRD was detected in 69% of patients at 1 month, 25% at 12 months, and 28% at 24 months from diagnosis. By univariate analysis, high levels of MRD at 1 month, or the presence of any detectable MRD at 12 or 24 months from diagnosis, were highly predictive of relapse. Multivariate analysis showed that MRD testing at 1 and 24 months each had independent prognostic significance. Intensified therapy at 12 months from diagnosis did not improve prognosis in those patients who were MRD positive at 12 months from diagnosis.
  
  
  CONCLUSIONS
  Clinical outcome in childhood ALL can be predicted with high accuracy by combining the results of MRD testing at 1 and 24 months from diagnosis.
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Sydney Children's Hospital Randwick, Randwick 2031, Sydney, Australia.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Marshall
authors.forename: Michelle
authors.initials: M
authors.lastname: Haber
authors.forename: Edward
authors.initials: E
authors.lastname: Kwan
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Daniella
authors.initials: D
authors.lastname: Ferrara
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Xue
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brisco
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Sykes
authors.forename: Alexander
authors.initials: A
authors.lastname: Morley
authors.forename: Boyd
authors.initials: B
authors.lastname: Webster
authors.forename: Luciano
authors.initials: L
authors.lastname: Dalla Pozza
authors.forename: Keith
authors.initials: K
authors.lastname: Waters
authors.forename: Murray D
authors.initials: MD
authors.lastname: Norris
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents