title: Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study.
abstract: OBJECTIVE
  Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration.
  
  
  METHODS
  Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window.
  
  
  RESULTS
  Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported.
  
  
  CONCLUSIONS
  Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA. barredjc@musc.edu
authors.forename: Julio C
authors.initials: JC
authors.lastname: Barredo
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lauer
authors.forename: Amy
authors.initials: A
authors.lastname: Billett
authors.forename: Maryanne
authors.initials: M
authors.lastname: Marymont
authors.forename: Jeanette
authors.initials: J
authors.lastname: Pullen
authors.forename: Bruce
authors.initials: B
authors.lastname: Camitta
authors.forename: Naomi
authors.initials: N
authors.lastname: Winick
authors.forename: William
authors.initials: W
authors.lastname: Carroll
authors.forename: A Kim
authors.initials: AK
authors.lastname: Ritchey
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D016019:Survival Analysis; D016896:Treatment Outcome