大剂量重组人α-2b干扰素治疗晚期黑色素瘤的疗效及对血清LDH、TIL和PD-L1表达的影响  

Efficacy of High-dose Recombinant Human Interferonα-2b in Patients with Advanced Melanoma on Expressions of LDH,TIL and PD-L1

作　　者：程芳[1] 郑炜[1] 安丽辉 孙玉姣 Cheng Fang;Zheng Wei;An Lihui;Sun Yujiao(Xingtai People's Hospital of Hebei,Xingtai 054000,China)

机构地区：[1]河北省邢台市人民医院,河北邢台054000

出　　处：《中国中西医结合皮肤性病学杂志》2021年第1期27-31,共5页Chinese Journal of Dermatovenereology of Integrated Traditional and Western Medicine

基　　金：河北省邢台市科技计划项目(编号:2016ZC297)。

摘　　要：目的探讨大剂量重组人α-2b干扰素联合常规化疗在晚期黑色素瘤患者中的应用安全性和有效性,以及对血清乳酸脱氢酶(LDH)、肿瘤浸润淋巴细胞(TIL)和抗程序性死亡因子配体1(PD-L1)表达的影响。方法回顾性总结2016年8月—2018年8月入我院确诊为晚期黑色素瘤患者共86例(Ⅲ期51例和Ⅳ期35例),均接受大剂量重组人α-2b干扰素(3~9×106 U皮下注射,第3、6、9天)联合常规化疗(达卡巴嗪+顺铂+长春新碱+阿霉素),21 d为1个疗程,至少进行4个疗程。根据实体瘤临床疗效评估标准于化疗结束后1个月进行,根据世界卫生组织化疗不良反应评估安全性;根据临床疗效(完全缓解、部分缓解、稳定和进展)将入组患者分为有效组(完全缓解、部分缓解、稳定)和无效组(进展),比较2组患者治疗前后血清LDH、TIL和PD-L1水平的变化特点。结果86例患者化疗1个月后完全缓解30例,部分缓解23例,稳定20例,进展13例,总有效率84.9%(73/86)。与无效组比较,有效组患者治疗前和治疗后血清LDH水平均明显下降,TIL和PD-L1水平升高(P<0.05);有效组治疗后血清LDH水平与治疗前比较也明显下降,TIL和PD-L1水平增加(P<0.05);但无效组治疗前和治疗后变化不明显(P>0.05)。采用多因素Logistic回归分析发现,治疗前血清LDH、TIL和PD-L1水平是预测临床疗效的独立因素(P<0.05)。86例患者随访中位时间16.5个月,经生存曲线分析发现,无疾病进展生存期6.5个月,中位生存期22.6个月。至随访截止时,86例患者中总生存率87.2%(75/76)。化疗并发症共17例,发生率19.8%(17/86)。结论大剂量重组人α-2b干扰素联合常规化疗在晚期黑色素瘤患者中有较好的应用安全性和有效性,化疗前后血清较高水平LDH、较低水平TIL和PD-L1提示较差的化疗反应和临床疗效,血清LDH、TIL和PD-L1可作为晚期黑色素瘤免疫抑制治疗的重要分子标志物。Objective In order to investigate safety and efficacy of high-dose recombinant human interferonα-2b combined with conventional chemotherapy in patients with advanced melanoma,and effects on expression of serum lactate dehydrogenase(LDH),tumor infiltrating lymphocyte(TIL)and anti-programmed death factor ligand 1(PD-L1).Method A retrospective review of 86 patients with advanced melanoma from August 2016 to August 2018 were enrolled,51 cases of tumor-node-metastasis(TNM)stageⅢand 35 cases of stageⅣ,they all received high dose recombinant human interferonα-2b(3~9×106 U subcutaneous injection,day 3,day 6 and day 9)combined with conventional chemotherapy(Dacarbazine+cisplatin+Vincristine+adriamycin),21 days for one course,at least four courses.One month after the end of chemotherapy,clinical efficacy and safety were evaluated.They were divided into effective group and ineffective group.Serum LDH,TIL and PD-L1 levels were compared in the two groups before and after treatment.Results There were 30 cases of complete remission,23 cases of partial remission,20 cases of stability,13 cases of progress,total effective rate was 84.9%(73/86).There were no significant differences in sex,age,tumor stage and maximum diameter in effective group and ineffective group(P>0.05),but serum LDH level in effective group before and after treatment was lower than that in ineffective group,and levels of TIL and PD-L1 increased(P<0.05),serum LDH level in effective group decreased after treatment than before,TIL and PD-L1 levels increased(P<0.05),but the changes in ineffective group were not obvious(P>0.05).The levels of LDH,TIL and PD-L1 were independent factors to predict clinical effect by multivariate logistic regression analysis(P<0.05).The median follow-up time of 86 patients was 16.5 months,disease-free progression survival time was 6.5 months,total survival time was 22.6 months,total survival rate was 87.2%(75/76).There were up to 17 cases of chemotherapy complications,complications rate was 19.8%(17/86).Conclusion High-dose recom

关 键 词：重组人Α-2B干扰素 晚期黑色素瘤 免疫抑制治疗 乳酸脱氢酶 肿瘤浸润淋巴细胞 抗程序性死亡因子配体1 

分 类 号：R739.5[医药卫生—肿瘤]