Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

Abstract

Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers. This retrospective study is designed to evaluate whether elderly GBM patients (age ≥65) develop similar TRL after RT/TMZ and whether such TRL is associated with decreased survival. Serial total lymphocyte counts (TLC) were retrospectively reviewed in patients (age ≥65) with newly diagnosed GBM undergoing RT/ TMZ and associated with treatment outcomes. Seventy-two patients were eligible: median KPS 70, median age 71 years (range 65–86) with 56 % of patients >70 years, 53 % female, 31 % received RT ≤45 Gy. Baseline median TLC was 1100 cells/mm3 which fell by 41 % to 650 cells/ mm3 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm3 at 2 months had a shorter survival than those with higher TLCs with a median overall survival of 4.6 versus 11.6 months, respectively. Multivariate analysis revealed a significant association between TRL and survival (HR 2.76, 95 % CI 1.30–5.86, p = 0.008). Treatment-related lymphopenia is frequent, severe, and an independent predictor for survival in elderly patients with GBM. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes. Prospective studies are needed to confirm these findings suggesting that immune preservation is important in this cancer.

Lymphopenia that may develop in patients treated with temozolomide and immune control check-point inhibitor may be a high risk for mortality during the COVID-19 outbreak

“…Before treatment, lymphopenia was found to be a poor prognostic indicator in many cancers. Similarly, data obtained indicate the poor prognosis of lymphopenia developing due to treatment in non-small cell lung cancer, head and neck cancer, glioblastoma, and pancreatic cancer [3].…”

Systemic Intravenous Adoptive Transfer of Autologous Lymphokine-activated αβ T Cells Improves Temozolomideinduced Lymphopenia in Patients with Glioma

“…Next, we examined the effects of the injected αβ T-cells on the patients' immunological status. It is reported that RT/temozolomide therapy sometimes causes serious treatment-related lymphopenia (17)(18)(19), and preferentially reduces the proportion of CD4 + T-cells (17). In addition, radiation therapy with steroids induces a decrease in CD4 + T-cells (20).…”

“…In addition, radiation therapy with steroids induces a decrease in CD4 + T-cells (20). Findings indicate that such temozolomide and/or radiation therapy-induced lymphopenia is related to a poor prognosis (17)(18)(19)(20). An NLR >4 before treatment (21) or prior to a second surgery (22) is also a poor prognostic factor for GBM.…”

Immunological effects of chemotherapy and radiotherapy against brain tumors

“…Results of a retrospective study suggest an association of treatment-related lymphopenia due to radiochemotherapy with reduced overall survival in elderly glioblastoma patients (43). (57).…”