Severe Lymphopenia after Chemoradiation Treatment is Associated with Worse Survival in Patients with Newly Diagnosed GBM

Abstract

To investigate the rate of lymphopenia after receiving definitive adjuvant chemoradiation therapy (CRT) for glioblastoma (GBM) patients and potential effects on clinical outcomes. We conducted a retrospective review of GBM patients treated with definitive adjuvant CRT at our institution covering a period from 2008 to 2016. We identified 96 patients with sufficient details regarding their treatment course as well as complete blood count with differential at approximately 1 month after completion of adjuvant CRT and subsequent follow-up information. Lymphopenia was determined as lymphocyte count <850 cells/μL (severe lymphophenia defined as lymphocyte count <400 cells/μL, mild-moderate lymphopenia≥400 cells/ μL and <850 cells/μL), while pancytopenia was determined as lymphopenia plus leukopenia (WBC<3.8x103/μL), anemia (RBC<4.2x106/μL), and thrombocytopenia (platelet<140x103). We measured overall survival (OS) as well as progression-free survival (PFS). We performed summary statistics on baseline patient characteristics as well as Kaplan-Meier analysis for outcomes with log-rank test to compare subgroups. Of the 96 patients, 51 (53.5%) were male, and 45 (46.9%) were female. Median age at start of RT was 61 years old (range 33 to 88). Median follow-up was 16.8 months (range 2.3 to 61.1). Seven (7.3%) patients were still alive at time of writing, of which five had evidence of recurrence, leaving only two (2.1%) which remained disease free. Lymphopenia at 1 month post-RT was observed in 55 (57.3%) of patients, of which 13 patients (13.5%) had severe lymphopenia. Four patients (4.2%) had lymphopenia occurring in the setting of pancytopenia. Median OS for all patients was 16.5 months, with 1 year OS at 69.8% and 2 year OS at 29.9%. When comparing subgroups of patients with lymphopenia vs without, there was no significant difference in OS or PFS. The median OS was 16.5 mos vs 18 mos, with 1 year OS at 67.3% vs 73.2%, and 2 year OS at 32.5% vs 26.9%, respectively (p=0.68). Median PFS for all patients was 6.7 months, with 1 year PFS at 25% and 2 year PFS at 7.3%. For patients with lymphopenia vs without, median PFS was 6.2 mos vs 6.9 mos, with 1 year PFS at 30.9% vs 17.1%, and 2 year PFS at 9.1% vs 4.9%, respectively (p=0.34). For patients with severe lymphopenia, overall survival was worse, with median OS of 8.4 mos, 1 year OS was 46.1% and 2 year OS was 15.3%, with significantly worse prognosis when compared to patients without lymphopenia (p=0.041) as well as with those with mild-moderate lymphopenia (p=0.024). Median PFS for severe lymphopenia patients was 5.5 mos, with 1 year PFS of 23.1% and 2 year PFS at 7.7% with no statistically significant difference amongst subgroup comparison (p>0.05). Severe lymphopenia appears to have a negative impact on overall survival for GBM patients and should be considered as a prognostic factor for clinical outcomes.