Importance Host-related immune factors have been implicated in the development and progression of diverse malignant neoplasms. Identifying associations between immunologic laboratory parameters and overall survival may inform novel prognostic biomarkers and mechanisms of antitumor immunity in localized bone and soft tissue sarcoma.

Objective To assess whether lymphopenia at diagnosis is associated with overall survival among patients with localized bone and soft tissue sarcoma.

Design, Setting, and Participants This retrospective cohort study analyzed patients from the Stanford Cancer Institute with localized bone and soft tissue sarcoma between September 1, 1998, and November 1, 2018. Patients were included if laboratory values were available within 60 days of diagnosis and, if applicable, prior to the initiation of chemotherapy and/or radiotherapy. Statistical analysis was performed from January 1, 2019, to November 1, 2020.

Exposures Absolute lymphocyte count within 60 days of diagnosis and antimicrobial exposure, defined by the number of antimicrobial agent prescriptions and the cumulative duration of antimicrobial administration within 60 days of diagnosis.

Main Outcomes and Measures The association between minimum absolute lymphocyte count at diagnosis and 5-year overall survival probability was characterized with the Kaplan-Meier method and multivariate Cox proportional hazards regression models. Multivariable logistic regressions were fitted to evaluate whether patients with lymphopenia were at greater risk of increased antimicrobial exposure.

Results Among 634 patients, the median age at diagnosis was 53.7 years (interquartile range, 37.5-66.8 years), and 290 patients (45.7%) were women, with a 5-year survival probability of 67.9%. There was a significant inverse association between lymphopenia at diagnosis and overall survival (hazard ratio [HR], 1.82; 95% CI, 1.39-1.40), resulting in a 13.5% 5-year survival probability difference compared with patients who did not have lymphopenia at diagnosis (60.2% vs 73.7% for those who never had lymphopenia). In addition, poorer survival was observed with higher-grade lymphopenia (grades 3 and 4: HR, 2.44; 95% CI, 1.68-3.55; grades 1 and 2: HR, 1.60; 95% CI, 1.18-2.18). In an exploratory analysis, patients with increased antibiotic exposure were more likely to have lymphopenia (odds ratio, 1.96; 95% CI, 1.26-3.07 for total number of antimicrobial agents; odds ratio, 1.70; 95% CI, 1.10-2.57 for antimicrobial duration) than antimicrobial-naive patients.

Conclusions and Relevance This study suggests that an abnormally low absolute lymphocyte count at diagnosis is associated with higher mortality among patients with localized bone and soft tissue sarcoma; therefore, lymphopenia may serve as a reliable prognostic biomarker. Potential mechanisms associated with host immunity and overall survival include a suppressed antitumor response and increased infectious complications, which merit future investigation.

重要性 与宿主相关的免疫因子已参与多种恶性肿瘤的发生和发展。鉴定免疫学实验室参数和总体存活率之间的关联可能会为局部骨和软组织肉瘤中的新型预后生物标志物和抗肿瘤免疫机制提供信息。

目的 评估局部骨和软组织肉瘤患者在诊断时的淋巴细胞减少是否与总体生存相关。

设计，背景和参与者 这项回顾性队列研究分析了斯坦福癌症研究所1998年9月1日至2018年11月1日间局部骨和软组织肉瘤的局部患者。如果在诊断和诊断后60天内可获得实验室数据，则将患者包括在内。 （如果适用），在开始化疗和/或放疗之前。从2019年1月1日到2020年11月1日进行统计分析。

暴露 诊断后60天内的绝对淋巴细胞计数和抗菌药物暴露，这由抗菌药物处方的数量和诊断60天内抗菌药物的累积使用时间定义。

主要结果和措施 使用Kaplan-Meier方法和多变量Cox比例风险回归模型对诊断时的最低淋巴细胞绝对数与5年总生存率之间的关联进行了表征。进行多变量logistic回归分析，以评估淋巴细胞减少症患者是否有更大的增加抗生素暴露的风险。

结果 在634例患者中，诊断时的中位年龄为53.7岁（四分位间距为37.5-66.8岁），女性为290例患者（45.7％），5年生存率为67.9％。诊断时的淋巴细胞减少与总生存率之间存在显着的负相关关系（危险比[HR]，1.82； 95％CI，1.39-1.40），与没有淋巴细胞减少的患者相比，其5年生存率差异为13.5％。在诊断时（60.2％比从未淋巴减少的患者为73.7％）。此外，高级别的淋巴细胞减少症观察到较差的生存率（3级和4级：HR，2.44； 95％CI，1.68-3.55； 1级和2级：HR，1.60； 95％CI，1.18-2.18）。在一项探索性分析中，抗生素暴露量增加的患者更容易出现淋巴细胞减少症（抗菌药物总数的比值比为1.96； 95％CI为1.26-3.07；比值比为1.70; 95％CI，抗菌持续时间为1.10-2.57）。

结论与相关性 这项研究表明，在局部骨和软组织肉瘤患者中，诊断时绝对淋巴细胞计数异常低与死亡率较高有关。因此，淋巴细胞减少症可以作为可靠的预后生物标志物。与宿主免疫力和总体存活率相关的潜在机制包括抗肿瘤反应抑制和感染并发症增加，值得进一步研究。