title: Outcome of CNS disease at diagnosis in disseminated small noncleaved-cell lymphoma and B-cell leukemia: a Children's Cancer Group study.
abstract: OBJECTIVE
  To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children's Cancer Group trials.
  
  
  METHODS
  Of 462 patients with disseminated disease, 49 (10.6%) had CNS disease at diagnosis (CNS+). CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies (CSF+/Mass; CNPs) in 36 patients and isolated CNPs in 13. Of the CNS+ patients, 28 had M2 (5% to 25% blasts) or M3 (> 25% blasts) bone marrow involvement. All patients received protocol-based systemic and intrathecal chemotherapy. Thirty-six patients also received CNS irradiation.
  
  
  RESULTS
  Relapses occurred in 21 (43%) of 49 patients, predominantly in the CNS (71%) and bone marrow (52%). The 3-year event-free survival +/- SE for all patients with CNS+ disease was 45% +/- 7%. Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase (LDH) diagnosis, with a relative failure rate (RFR) of 1.52 (95% confidence interval [CI], 0.88 to 2.6; P =.15). In comparison, the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 (95% CI, 0.96 to 2.0; P =.029) and 2.2 (95% CI, 1.5 to 3.0; P <.001), respectively. The RFR for patients with isolated CNPs was 0.87 (95% CI, 0.36 to 2.1; P =.76).
  
  
  CONCLUSIONS
  We conclude that, with the treatments used during the period covered by these studies, the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level, but the effect was not statistically significant.
authors.affiliation: Memorial Sloan-Kettering Cancer Center and New York University Medical Center, New York, NY, USA. gururooz@mc.duke.edu
authors.forename: S
authors.initials: S
authors.lastname: Gururangan
authors.forename: R
authors.initials: R
authors.lastname: Sposto
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
authors.forename: J L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate