title: Response of children with high-risk acute lymphoblastic leukemia treated with and without cranial irradiation: a report from the Children's Cancer Group.
abstract: OBJECTIVE
  Intensified intrathecal (i.t.) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either i.t. methotrexate (MTX) and CRT or intensified i.t. MTX alone.
  
  
  METHODS
  Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count > or = 50,000/microL or age > or = 10 years, excluding those with lymphomatous features) who achieved an RER (< or = 25% marrow blasts on day 7) to induction therapy and lacked CNS disease at diagnosis were randomized to receive systemic therapy with either i.t. MTX and CRT (regimen A, n = 317) or intensified i.t. MTX alone (regimen B, n = 319).
  
  
  RESULTS
  Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% +/- 4.0% (SD)and 70.4% +/- 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% +/- 3.4% and 75.0% +/- 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B.
  
  
  CONCLUSIONS
  For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either i.t. MTX plus CRT or intensified i.t. MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified i.t. MTX may protect against late bone marrow relapse.
authors.affiliation: Department of Pediatric Hematology-Oncology, University of Chicago, IL, USA. jnachman@babies.bsd.uchicago.edu
authors.forename: J
authors.initials: J
authors.lastname: Nachman
authors.forename: H N
authors.initials: HN
authors.lastname: Sather
authors.forename: J M
authors.initials: JM
authors.lastname: Cherlow
authors.forename: M G
authors.initials: MG
authors.lastname: Sensel
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: J N
authors.initials: JN
authors.lastname: Lukens
authors.forename: L
authors.initials: L
authors.lastname: Wolff
authors.forename: M E
authors.initials: ME
authors.lastname: Trigg
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D016016:Proportional Hazards Models; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate