title: Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide.
abstract: OBJECTIVE
  Patients with high-grade gliomas (HGG) routinely receive radiation, temozolomide, and glucocorticoids. As each of these is immunosuppressive, we conducted a prospective, multicenter study to follow CD4 counts over time and determine whether low CD4 counts were associated with adverse outcomes.
  
  
  METHODS
  Patients with newly diagnosed HGG had CD4 counts drawn before initiating standard therapy and monthly thereafter for 1 year. Information on hospitalizations, infections, glucocorticoid use, survival, and cause of death were also collected.
  
  
  RESULTS
  Ninety-six evaluable patients were accrued [85% glioblastoma, median age of 57, median Karnofsky performance status (KPS) = 90]. The median CD4 count before radiation and temozolomide treatment was 664 cells/mm(3). The CD4 count nadir occurred 2 months after initiating therapy when 73% of patients had CD4 counts less than 300 cells/mm(3) and 40% had less than 200 cells/mm(3). CD4 counts remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm(3)at 2 months had shorter survival than those with higher counts (median: 13.1 vs. 19.7 months, P = 0.002). Median survival was related to CD4 toxicity grades (I = 23.8 months, II = 19.7 months, III-IV = 13.1 months, P = 0.009). The adjusted HR for death attributable to 2-month CD4 count below 200 was 1.66 (P = 0.03). Eighty-eight percent of deaths resulted from disease progression, whereas only 2.5% were due to infection.
  
  
  CONCLUSIONS
  Severe reductions in CD4 counts in patients with newly diagnosed HGG treated with radiation and temozolomide treatment are common, treatment-related, long-lasting, and associated with early death from tumor progression.
authors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, Maryland 21231, USA. grossman@jhmi.edu
authors: Stuart A
authors: SA
authors: Grossman
authors: Xiaobu
authors: X
authors: Ye
authors: Glenn
authors: G
authors: Lesser
authors: Andrew
authors: A
authors: Sloan
authors: Hetty
authors: H
authors: Carraway
authors: Serena
authors: S
authors: Desideri
authors: Steven
authors: S
authors: Piantadosi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018791:CD4 Lymphocyte Count; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007165:Immunosuppression Therapy; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D017063:Outcome Assessment, Health Care / Q000379:methods; D011446:Prospective Studies; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide