title: Long-term evaluation of a CNS prophylaxis trial--treatment comparisons and outcome after CNS relapse in childhood ALL: a report from the Childrens Cancer Study Group.
abstract: The current status of children with acute lymphoblastic leukemia (ALL) who had developed CNS disease while being treated on protocol CCG-101 was investigated. Seven hundred thirty-six eligible patients were entered into the study between June 1972 and July 1974. All children who were greater than 18 months of age were eligible for randomization to a CNS prophylaxis trial for which one regimen gave only a short course of intrathecal methotrexate (IT MTX) as prophylaxis. All other regimens included radiation therapy as prophylaxis. Current follow-up (median, greater than 10 years) shows no significant difference by standard life-table analysis for ultimate survival, although a substantial excess of CNS episodes occurred on the IT MTX regimen. Of the 675 patients who completed induction therapy and achieved remission in the study, 100 (14.8%) developed CNS disease as the first evidence of relapse. Fifty-five of these 100 had no subsequent CNS episodes. Only 17 of these 55 patients are surviving without further relapses since the CNS episode. The median time to isolated CNS relapse was 457 days. Time to the initial CNS relapse was found to be the most important factor for predicting outcome. Thirty-five of the 55 patients with isolated relapse subsequently relapsed in the bone marrow, and of these, 32 have died. Twenty patients of the 100 with CNS disease as the first evidence of relapse developed two episodes of CNS involvement and 17 of these 20 patients subsequently relapsed in the bone marrow; only one patient survived. Twenty-five patients of the 100 have shown a pattern of chronic CNS disease with multiple CNS relapses. The overall disease-free survival for the 100 patients who developed one or more relapse was only 16%. These data demonstrate that the occurrence of a CNS relapse is an indicator of poor subsequent outcome. Comparison of results of groups receiving different CNS prophylaxis required careful consideration of the entire pattern of relapses and mortality.
authors.affiliation: Childrens Hospital of Los Angeles, CA.
authors.forename: J A
authors.initials: JA
authors.lastname: Ortega
authors.forename: M E
authors.initials: ME
authors.lastname: Nesbit
authors.forename: H N
authors.initials: HN
authors.lastname: Sather
authors.forename: L L
authors.initials: LL
authors.lastname: Robison
authors.forename: G J
authors.initials: GJ
authors.lastname: D'Angio
authors.forename: G D
authors.initials: GD
authors.lastname: Hammond
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D006801:Humans; D007278:Injections, Spinal; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000532:radiotherapy*; D008577:Meningeal Neoplasms / Q000188:drug therapy; D008727:Methotrexate / Q000627:therapeutic use; D011897:Random Allocation; D013120:Spinal Cord Neoplasms / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D008727:Methotrexate