title: Treating childhood acute lymphoblastic leukemia without cranial irradiation.
abstract: BACKGROUND
  Prophylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse.
  
  
  METHODS
  We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted from treatment in all children with newly diagnosed ALL. A total of 498 patients who could be evaluated were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission-induction treatment. The duration of continuous complete remission in the 71 patients who previously would have received prophylactic cranial irradiation was compared with that of 56 historical controls who received it.
  
  
  RESULTS
  The 5-year event-free and overall survival probabilities for all 498 patients were 85.6% (95% confidence interval [CI], 79.9 to 91.3) and 93.5% (95% CI, 89.8 to 97.2), respectively. The 5-year cumulative risk of isolated CNS relapse was 2.7% (95% CI, 1.1 to 4.3), and that of any CNS relapse (including isolated relapse and combined relapse) was 3.9% (95% CI, 1.9 to 5.9). The 71 patients had significantly longer continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remained in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blast cells at diagnosis and a high level of minimal residual disease (> or = 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection.
  
  
  CONCLUSIONS
  With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted from the treatment of childhood ALL. (ClinicalTrials.gov number, NCT00137111.)
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. ching-hon.pui@stjude.org
authors: Ching-Hon
authors: CH
authors: Pui
authors: Dario
authors: D
authors: Campana
authors: Deqing
authors: D
authors: Pei
authors: W Paul
authors: WP
authors: Bowman
authors: John T
authors: JT
authors: Sandlund
authors: Sue C
authors: SC
authors: Kaste
authors: Raul C
authors: RC
authors: Ribeiro
authors: Jeffrey E
authors: JE
authors: Rubnitz
authors: Susana C
authors: SC
authors: Raimondi
authors: Mihaela
authors: M
authors: Onciu
authors: Elaine
authors: E
authors: Coustan-Smith
authors: Larry E
authors: LE
authors: Kun
authors: Sima
authors: S
authors: Jeha
authors: Cheng
authors: C
authors: Cheng
authors: Scott C
authors: SC
authors: Howard
authors: Vickey
authors: V
authors: Simmons
authors: Amy
authors: A
authors: Bayles
authors: Monika L
authors: ML
authors: Metzger
authors: James M
authors: JM
authors: Boyett
authors: Wing
authors: W
authors: Leung
authors: Rupert
authors: R
authors: Handgretinger
authors: James R
authors: JR
authors: Downing
authors: William E
authors: WE
authors: Evans
authors: Mary V
authors: MV
authors: Relling
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D008727:Methotrexate; D003630:Daunorubicin