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/mm(3) which fell by 41% to 650 cells/mm(3) 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm(3) 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.

Keywords: Chemotherapy; Glioblastoma; Lymphopenia; Radiation; Treatment-related toxicities.

Fig. 1

Treatment related lymphopenia is common, severe, and long-lasting in elderly GBM patients treated with chemo/RT. Median TLC over a 12-month period after initiation of chemo/RT (n = 72). The median TLCs were normal prior to chemo/RT. However, 2 months after initiation of concurrent chemo/RT, the median TLC fell rapidly by 41 % (p < 0.0001)

Fig. 2

Severe treatment-related lymphopenia in elderly patients with GBM is associated with reduced overall survival. Kaplan–Meier survival curves for elderly patients with GBM who have undergone chemo/RT are depicted below. Patients who developed severe treatment-related lymphopenia (TLC<500 cells/mm³) 2 months after beginning chemo/RT had a significant shorter median overall survival than those whose TLC were ≥500 cells/mm³ (multivariate analysis HR 2.76, 95 %CI 1.30–5.86, p = 0.008)