title: CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance.
  
  
  METHODS
  We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage).
  
  
  RESULTS
  Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease.
  
  
  CONCLUSIONS
  A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.
authors.affiliation: Departments of Hematology/Oncology, Radiation Therapy, Pathology and Laboratory Medicine, and Biostatistics, St Jude Children's Research Hospital, and University of Tennessee at Memphis, College of Medicine, Memphis, TN, USA. john.sandlund@stjude.org
authors.forename: J T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: S B
authors.initials: SB
authors.lastname: Murphy
authors.forename: V M
authors.initials: VM
authors.lastname: Santana
authors.forename: F
authors.initials: F
authors.lastname: Behm
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: C W
authors.initials: CW
authors.lastname: Berard
authors.forename: W L
authors.initials: WL
authors.lastname: Furman
authors.forename: R
authors.initials: R
authors.lastname: Ribeiro
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: C
authors.initials: C
authors.lastname: Greenwald
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Walter
authors.forename: C H
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000209:etiology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D003389:Cranial Nerve Diseases / Q000209:etiology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D015552:Injections, Intralesional; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016403:Lymphoma, Large B-Cell, Diffuse / Q000134:cerebrospinal fluid / Q000150:complications / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000150:complications / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007770:L-Lactate Dehydrogenase