title: Does the early intensification of intrathecal therapy improve outcomes in pediatric acute lymphoblastic leukemia patients with CNS2/TLP+ status at diagnosis?
abstract: OBJECTIVE
  We aimed to determine whether the addition of two extra intrathecal methotrexate (ITM) doses during induction in acute lymphoblastic leukemia (ALL) patients eliminate the prognostic significance of CNS2/TLP+ status.
  
  
  METHODS
  We retrospectively analyzed 224 patients according to the central nervous system (CNS) involvement at diagnosis: CNS1, CNS2, or CNS3. Patients with CNS2/TLP+ received two additional ITM doses during induction. Patients were treated according to the Children's Cancer Group (CCG)-1991/1961 protocols between January 2001 and December 2007.
  
  
  RESULTS
  The 5-year relapse-free survival (RFS) rates for the ALL patients in the CNS1, CNS2, and CNS3 groups were 80.4 ± 3.0, 100, and 73.5 ± 11.3%, respectively; a non-significant difference was observed between the groups (P = 0.063). However, the patients with CNS2 had significantly better survival compared with the CNS3 patients (P = 0.03). The 5-year cumulative incidence of relapse (CIR) rates for the three groups were 17 (95% confidence interval (CI): 11.9-22.9), 0, and 18.8% (95% CI: 4.3-41.1), respectively; (P = 0.214) and those of isolated or combined CNS relapse were 9.6 (95% CI: 5.8-14.5), 0 and 6.3% (95% CI: 0.3-25.8), respectively (P = 0.424).
  
  
  CONCLUSIONS
  This study shows that the intensification of ITM therapy during induction improves outcomes in patients with CNS2/TLP+ status and eliminates its prognostic significance. This suggests that early intensification using CNS-directed therapy is beneficial in controlling minimal CNS disease.
authors.forename: Wasil
authors.initials: W
authors.lastname: Jastaniah
authors.forename: Naglla
authors.initials: N
authors.lastname: Elimam
authors.forename: Khalid
authors.initials: K
authors.lastname: Abdalla
authors.forename: Taha M
authors.initials: TM
authors.lastname: Khattab
authors.forename: Sami
authors.initials: S
authors.lastname: Felimban
authors.forename: Mohammed B
authors.initials: MB
authors.lastname: Abrar
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007278:Injections, Spinal; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: ALL; CNS; CNS2; Outcome; Traumatic lumbar puncture