Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis

Abstract

Background: Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma.Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis.Results: A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3–40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9–34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2–38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74–2.27; P< 0.001) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose > 2 mg instead of baseline use were risk factors for lymphopenia.Conclusions: Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.

Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients

“…Lymphopenia has been observed to correlate with poor patient outcomes (9,36). In our study, contrary to previous studies, we initially observed a significant univariate correlation between post-radiation lymphopenia and improved survival (Supplementary Figure 1, Supplementary Table 2).…”

“…Neutrophils have been associated with increased resistance to radiation and poor cancer patient outcomes. Furthermore, elevated neutrophil-to-lymphocyte ratios (NLR > 4.0) have also been observed to be a poor prognostic indicator in glioma patients (8)(9)(10). Thus, we evaluated the effects of neutrophils and neutrophilia on survival.…”

“…Observed markers include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-tolymphocyte ratio (MLR) or lymphocyte-to-monocyte ratio (LMR) (8). However, despite multiple retrospective studies and systematic reviews, no consensus has been reached for which markers, especially those related to platelets and monocytes, consistently predict for poor prognosis (8)(9)(10)(11). Furthermore, the prognostic role of absolute hematologic cell counts, especially those in the intra-or post-treatment time intervals, is not well understood in glioma patients.…”

Observational study on antibody response to COVID-19 Vaccines in pAtients with gastro-entero-panCreatic Cancers and neuroendocrIne NeoplAsms on systemic TreatmEnts (VACCINATE).

“…Another explanation may be that not all the regimens used to treat our population are associated with a real lymphocytes dysfunction. In fact, the sample consisted of NEN patients treated with temozolomide and others previously receiving peptide receptor radioligand therapy (PRRT), which often result in deep, long-lasting low lymphocyte levels (30)(31)(32)(33)(34).…”

Epstein-barr Virus Negative Primary Central Nervous System Lymphoma Developed after Treatment of Glioblastoma: A Case Report

“… 14 ) It is well-known that temozolomide causes lymphopenia as part of myelotoxicity, and previous research indicates that the incidence of severe lymphopenia was 31.6% and that treatment-related lymphopenia is strongly correlated with poor overall survival, low response rate, and recurrences. 15 ) Furthermore, lymphopenia was reported to be a biomarker of impaired host immunity and a decreased low absolute lymphocyte count was a poor prognostic factor for patients with lymphoma and other cancers. 16 , 17 ) Thus, we postulate that lymphopenia might cause mild immunosuppressive status in our case, which might result in the development of non-Hodgkin's lymphoma.…”