title: CNS-directed therapy in young children with T-lineage acute lymphoblastic leukemia: High-dose methotrexate versus cranial irradiation.
abstract: BACKGROUND
  Prophylactic use of cranial radiation therapy (CRT) in young children with acute lymphoblastic leukemia (ALL) is associated with significant long-term morbidity. Therefore, current treatment protocols for pediatric B-precursor ALL have abandoned prophylactic CRT in favor of intrathecal chemotherapy, combined with either high-dose methotrexate infusions (HD-MTX) or intensive systemic chemotherapy. In contrast, prophylactic CRT continues to be used in children with T-lineage ALL (T-ALL), who historically have had an inferior prognosis. We conducted a retrospective cohort study to determine the effect on survival of substituting HD-MTX for CRT in young children with T-ALL, a group that faces a high risk of long-term sequelae from CRT.
  
  
  METHODS
  Twenty-six children, diagnosed with T-ALL between the ages of 1 and 5 years, were treated on the same high-risk leukemia protocol. Central nervous system (CNS) directed therapy consisted of either CRT (1,800 cGy) or HD-MTX (three doses of 8 g/m2), depending on the treatment era in which patients were diagnosed.
  
  
  RESULTS
  Of the 24 patients who entered remission, 12 received CRT and 12 received HD-MTX. Five-year event-free survival (EFS) (+/-SE) was 92 +/- 8% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.23). Five-year overall survival (OS) was 100% in the HD-MTX group versus 75 +/- 13% in the CRT group (P=0.07). There were no CNS recurrences in the HD-MTX group. One patient treated with CRT developed a brain tumor.
  
  
  CONCLUSIONS
  The use of HD-MTX instead of CRT as CNS-directed therapy in very young children with T-ALL does not compromise survival, while avoiding the adverse long-term effects of cranial irradiation.
authors.affiliation: Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children Research Institute, The University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Ronnen
authors.initials: R
authors.lastname: Maze
authors.forename: Brenda
authors.initials: B
authors.lastname: Spiegler
authors.forename: Mark L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Johann K
authors.initials: JK
authors.lastname: Hitzler
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000532:radiotherapy*; D002675:Child, Preschool; D015331:Cohort Studies; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D007223:Infant; D015458:Leukemia, T-Cell / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate