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

Stuart A Grossman, Xiaobu Ye, Glenn Lesser, Andrew Sloan, Hetty Carraway, Serena Desideri, Steven Piantadosi

Research output: Contribution to journalArticle

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/mm3. The CD4 count nadir occurred 2 months after initiating therapy when 73% of patients had CD4 counts less than 300 cells/mm3 and 40% had less than 200 cells/mm3. CD4 counts remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm3at 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.

Original languageEnglish (US)
Pages (from-to)5473-5480
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number16
DOIs
StatePublished - Aug 15 2011

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temozolomide
CD4 Lymphocyte Count
Glioma
Immunosuppression
Radiation
Glucocorticoids
Survival
Therapeutics
Karnofsky Performance Status

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. / Grossman, Stuart A; Ye, Xiaobu; Lesser, Glenn; Sloan, Andrew; Carraway, Hetty; Desideri, Serena; Piantadosi, Steven.

In: Clinical Cancer Research, Vol. 17, No. 16, 15.08.2011, p. 5473-5480.

Research output: Contribution to journalArticle

Grossman, Stuart A ; Ye, Xiaobu ; Lesser, Glenn ; Sloan, Andrew ; Carraway, Hetty ; Desideri, Serena ; Piantadosi, Steven. / Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 16. pp. 5473-5480.
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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/mm3. The CD4 count nadir occurred 2 months after initiating therapy when 73{\%} of patients had CD4 counts less than 300 cells/mm3 and 40{\%} had less than 200 cells/mm3. CD4 counts remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm3at 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.",
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AU - Desideri, Serena

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