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

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.

Figure 1

CD4 Count Trend over Time

Figure 2

Percent Decline in Hematologic Values over Time

Figure 3

Overall Survival by CD4 Count at 2 Months Legend for Figure 3: Survival in patients with CD4 counts <200 cells/mm³ at two months was substantially different from those with higher CD4 counts as measured by median survival (13.1 months (95% CI: 9.1–16.4) versus to 19.7 months (95% CI: 15.9–24.0)), log rank test (p=0.002, log-rank test), or the adjusted hazard ratio for death (1.66 (p=0.03)).