高级别脑胶质瘤患者在接受放疗和替莫唑胺化疗后的免疫抑制。
Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide.
机构信息
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
出版信息
Clin Cancer Res. 2011 Aug 15;17(16):5473-80. doi: 10.1158/1078-0432.CCR-11-0774. Epub 2011 Jul 7.
PURPOSE
Patients with high-grade gliomas (HGG) routinely receive radiation, temozolomide, and glucocorticoids. As each of these is immunosuppressive, we conducted a prospective, multicenter study to follow CD4 counts over time and determine whether low CD4 counts were associated with adverse outcomes.
EXPERIMENTAL DESIGN
Patients with newly diagnosed HGG had CD4 counts drawn before initiating standard therapy and monthly thereafter for 1 year. Information on hospitalizations, infections, glucocorticoid use, survival, and cause of death were also collected.
RESULTS
Ninety-six evaluable patients were accrued [85% glioblastoma, median age of 57, median Karnofsky performance status (KPS) = 90]. The median CD4 count before radiation and temozolomide treatment was 664 cells/mm(3). The CD4 count nadir occurred 2 months after initiating therapy when 73% of patients had CD4 counts less than 300 cells/mm(3) and 40% had less than 200 cells/mm(3). CD4 counts remained low throughout the year of follow-up. Patients with CD4 counts less than 200 cells/mm(3)at 2 months had shorter survival than those with higher counts (median: 13.1 vs. 19.7 months, P = 0.002). Median survival was related to CD4 toxicity grades (I = 23.8 months, II = 19.7 months, III-IV = 13.1 months, P = 0.009). The adjusted HR for death attributable to 2-month CD4 count below 200 was 1.66 (P = 0.03). Eighty-eight percent of deaths resulted from disease progression, whereas only 2.5% were due to infection.
CONCLUSIONS
Severe reductions in CD4 counts in patients with newly diagnosed HGG treated with radiation and temozolomide treatment are common, treatment-related, long-lasting, and associated with early death from tumor progression.
目的
高级别神经胶质瘤(HGG)患者通常接受放疗、替莫唑胺和糖皮质激素治疗。由于这些治疗都具有免疫抑制作用,我们进行了一项前瞻性、多中心研究,以跟踪 CD4 计数随时间的变化,并确定低 CD4 计数是否与不良预后相关。
实验设计
新诊断的 HGG 患者在开始标准治疗前和此后每月进行一次 CD4 计数,共 1 年。还收集了住院、感染、糖皮质激素使用、生存和死亡原因的信息。
结果
共纳入 96 例可评估患者[85%为胶质母细胞瘤,中位年龄 57 岁,中位 Karnofsky 表现状态(KPS)= 90]。放疗和替莫唑胺治疗前的中位 CD4 计数为 664 个细胞/mm³。治疗开始后 2 个月时,CD4 计数达到最低点,73%的患者 CD4 计数小于 300 个细胞/mm³,40%的患者 CD4 计数小于 200 个细胞/mm³。在整个随访期间,CD4 计数一直较低。2 个月时 CD4 计数小于 200 个细胞/mm³的患者比 CD4 计数较高的患者生存时间更短(中位:13.1 个月 vs. 19.7 个月,P=0.002)。中位生存时间与 CD4 毒性分级有关(I 级为 23.8 个月,II 级为 19.7 个月,III-IV 级为 13.1 个月,P=0.009)。归因于 2 个月时 CD4 计数低于 200 的死亡调整后的 HR 为 1.66(P=0.03)。88%的死亡是由于疾病进展,而只有 2.5%是由于感染。
结论
新诊断的接受放疗和替莫唑胺治疗的 HGG 患者 CD4 计数严重下降较为常见,是治疗相关的、持久的,与肿瘤进展导致的早期死亡有关。