title: Survival and neurocognitive outcomes after cranial or craniospinal irradiation plus total-body irradiation before stem cell transplantation in pediatric leukemia patients with central nervous system involvement.
abstract: OBJECTIVE
  To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen.
  
  
  METHODS
  Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes.
  
  
  RESULTS
  All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college.
  
  
  CONCLUSIONS
  The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hiniker
authors.affiliation: Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Rajni
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Modlin
authors.affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Gray
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Harris
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Lynn
authors.initials: L
authors.lastname: Million
authors.affiliation: Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California.
authors.forename: Eileen F
authors.initials: EF
authors.lastname: Kiamanesh
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California. Electronic address: sarah2@stanford.edu.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Donaldson
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000379:methods*; D061888:Craniospinal Irradiation / Q000379:methods; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000528:radiation effects; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D033581:Stem Cell Transplantation / Q000379:methods; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation / Q000379:methods*; D055815:Young Adult