IMCT-16SERIAL EVALUATION OF LYMPHOCYTE SUBSETS IN PATIENTS WITH NEWLY DIAGNOSED HIGH GRADE GLIOMAS TREATED WITH STANDARD RADIATION AND TEMOZOLOMIDE

Abstract

BACKGROUND: The immune system plays a significant role in cancer prevention and outcome. In high grade gliomas (HGG), severe lymphopenia is associated with shortened survival due to tumor progression. Here we report the first comprehensive study of serial changes in lymphocyte subsets in HGG following standard radiation (RT) and temozolomide (TMZ). METHODS: Adults (KPS > 60, HIV negative) with newly diagnosed HGG scheduled to receive standard RT and TMZ followed by adjuvant TMZ were eligible. Patients were enrolled at the Johns Hopkins Hospital and at Washington University. Blood was collected before beginning therapy and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Analysis of lymphocyte subsets was performed at NIH/NCI on a Beckman Coulter Gallios flow cytometer; T cell naive, memory and effector subsets were assessed within CD8, Treg and nonTreg CD4 T cells. Data was analyzed with FlowJo. RESULTS: All 20 patients have enrolled. Their median age is 53 years; baseline dexamethasone dose is 0.5 mg/day, and follow-up time is 9.5 months. 15% had lymphocyte counts < 1000 cells/mm3 before starting therapy. The most significant T-cell reductions were in naive CD4+ (60% of baseline at 26 weeks, p = 0.008) and CD4+ (49% of baseline at 26 weeks, p = 0.007) cells. CD8, Tregs, CD3, CD8 effector, and NK cells were less affected. B cells were also markedly reduced. The CD4 + /CD8+ ratio fell after RT/TMZ and remained low. CONCLUSIONS: This is the first comprehensive study to report serial trends in lymphocyte subsets following RT + TMZ. CD4+ and naive CD4+ T cells appear most affected and this lymphopenia is persistent after 9 months of follow up. This data provides insight into potential therapeutic approaches (i.e. IL-7) and the optimal timing for immunologic interventions in this patient population.