Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University Cancer Research Institute, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
J Neurooncol. 2019 Jun;143(2):321-328. doi: 10.1007/s11060-019-03167-2. Epub 2019 Apr 13.
Lymphopenia in patients with glioblastoma (GBM) is related to treatment as well as disease progression. This retrospective study investigated the prevalence, influencing factors, recoverability, and clinical significance of lymphopenia in GBM patients treated with concomitant chemoradiotherapy (CCRT).
A total of 219 patients with newly diagnosed GBM who had received at least 3 cycles of adjuvant temozolomide (TMZ) followed by CCRT with TMZ were enrolled. Serial data on complete blood cell counts, including differential cell counts, were collected just before a new phase and before every treatment cycle of the regimen. Relationships between white blood cell (WBC) variable changes and treatment modalities as well as survival were analyzed. Lymphopenia was classified using the definition of the Common Terminology Criteria for Adverse Events version 5.0.
A total of 92 patients (42.0%) showed decreased levels of lymphocytes (< 1500/µL) at baseline. The WBC count, absolute neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio were all significantly decreased after RT/TMZ treatment and did not recover during the adjuvant TMZ period. However, these metrics all began to recover 3 months after the last TMZ cycle, except for the lymphocyte count. The proportion of lymphopenia patients (< 1500 lymphocytes/µL) increased to 74.8% after RT/TMZ and remained steady at approximately 71.5% (range 63.7-75.3%) throughout the management period. Moreover, the number of patients with grade 3 lymphopenia (< 500 lymphocytes/µL) also increased significantly after treatment to reach 2.9% (from 0.9% at baseline). Statistically, 75.7% of lymphopenia patients were predicted to recover in a median time of 240.3 days (95% confidence interval ± 104.7 days) after TMZ withdrawal. There were no dose-dependent relationships between RT or TMZ and lymphopenia. Grade 3 (< 500 lymphocytes/µL) lymphopenia measured at 1 month after RT/TMZ predicted significantly reduced survival (13.0 months vs. 19.5 months, p = 0.011).
Lymphopenia is a frequent event during GBM disease progression and treatment. Treatment-related lymphopenia is profound and prolonged and can be used as a prognostic factor for GBM patients.
患有胶质母细胞瘤(GBM)的患者出现淋巴细胞减少与治疗和疾病进展有关。本回顾性研究调查了接受同步放化疗(CCRT)联合替莫唑胺(TMZ)治疗的 GBM 患者中淋巴细胞减少的发生率、影响因素、可恢复性和临床意义。
共纳入 219 例新诊断为 GBM 且至少接受 3 个周期辅助 TMZ 治疗后接受 CCRT 联合 TMZ 治疗的患者。在新治疗阶段前和每个治疗周期前,收集全血细胞计数(包括差异细胞计数)的连续数据。分析白细胞(WBC)变量变化与治疗方式和生存之间的关系。淋巴细胞减少根据不良事件通用术语标准 5.0 定义进行分类。
基线时有 92 例(42.0%)患者出现淋巴细胞水平下降(<1500/µL)。RT/TMZ 治疗后 WBC 计数、绝对中性粒细胞计数、淋巴细胞计数和中性粒细胞与淋巴细胞比值均显著下降,且在辅助 TMZ 期间未恢复。然而,除淋巴细胞计数外,所有这些指标在最后一个 TMZ 周期后 3 个月开始恢复。RT/TMZ 后,淋巴细胞减少症患者(<1500 个淋巴细胞/µL)的比例增加至 74.8%,并在整个治疗期间保持稳定在约 71.5%(范围 63.7-75.3%)。此外,治疗后 3 级(<500 个淋巴细胞/µL)淋巴细胞减少症患者的数量也显著增加,达到 2.9%(基线时为 0.9%)。统计分析显示,75.7%的淋巴细胞减少症患者在 TMZ 停药后中位时间 240.3 天(95%置信区间±104.7 天)内可恢复。RT 或 TMZ 与淋巴细胞减少症之间没有剂量依赖性关系。RT/TMZ 后 1 个月测量的 3 级(<500 个淋巴细胞/µL)淋巴细胞减少症预测显著降低生存(13.0 个月比 19.5 个月,p=0.011)。
淋巴细胞减少是 GBM 疾病进展和治疗过程中的常见事件。治疗相关的淋巴细胞减少症是严重且持久的,并可作为 GBM 患者的预后因素。