Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide

Clin Cancer Res. 2011 Aug 15;17(16):5473-80. doi: 10.1158/1078-0432.CCR-11-0774. Epub 2011 Jul 7.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • CD4 Lymphocyte Count
  • Chemoradiotherapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Follow-Up Studies
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunosuppression Therapy*
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status / statistics & numerical data
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Outcome Assessment, Health Care / methods
  • Prospective Studies
  • Temozolomide
  • Time Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide