重组人粒-巨噬细胞集落刺激因子联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤效果观察

目的:观察重组人粒-巨噬细胞集落刺激因子（rhGM-CSF）联合R-CHOP方案治疗初治弥漫大B细胞淋巴瘤的临床效果及安全性。方法:回顾性分析2017年2月至2019年11月海军军医大学（第二军医大学）长海医院39例接受rhGM-CSF联合R-CHOP方案及39例接受R-CHOP方案治疗的初治DLBCL患者的临床资料，比较两组患者的总反应率（ORR）、完全缓解（CR）率、总生存（OS）、无进展生存（PFS）及不良反应发生情况。结果:rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的ORR分别为87.2%（34/39）、82.1%（32/39），差异无统计学意义（ χ2=0.394， P=0.53），CR率分别为71.8%（28/39）、56.4%（22/39），差异亦无统计学意义（ χ2=2.006， P=0.157）。随访截至2020年9月19日，rhGM-CSF联合R-CHOP方案组生存32例，死亡7例，其中1例死于肠癌，原发病仍处于CR状态；R-CHOP方案组生存32例，死亡7例。rhGM-CSF联合R-CHOP方案组及R-CHOP方案组2年OS率分别为82.5%、73.9%（ χ2=0.038， P=0.845），2年PFS率分别为67.1%、55.2%（ χ2=0.457， P=0.499）。亚组分析结果显示，rhGM-CSF联合R-CHOP方案组及R-CHOP方案组的生发中心B细胞型亚组间、非生发中心B细胞型亚组间、Lugano分期Ⅰ~Ⅱ期亚组间、Lugano分期Ⅲ~Ⅳ期亚组间、年龄<60岁亚组间、年龄≥60岁亚组间CR率分别比较，差异均无统计学意义（均 P>0.05）。主要不良反应为骨髓抑制及其所致感染，两组3~4级血液学不良反应及感染发生率比较，差异均无统计学意义（均 P>0.05）。予支持治疗后，所有患者均安全度过骨髓抑制期，无治疗相关死亡。 结论:rhGM-CSF联合R-CHOP方案用于初治DLBCL患者安全有效。

Efficacy observation of recombinant human granulocyte macrophage stimulating factor combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma

Objective:To observe the clinical efficacy and safety of recombinant human granulocyte macrophage stimulating factor (rhGM-CSF) combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 39 patients with newly diagnosed DLBCL treated with rhGM-CSF combined with R-CHOP regimen, and 39 patients with newly diagnosed DLBCL treated with R-CHOP regimen in Naval Medical University (Changhai Hospital) from February 2017 to November 2019 were retrospectively analyzed. The total response rate (ORR), remission rate (CR) rate, overall survival (OS), progression-free survival (PFS) and adverse reactions of both groups were compared.Results:In rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group, ORR was 87.2% (34/39) and 82.1% (32/39), respectively, and the difference was statistically significant ( χ2 = 0.394, P = 0.53); CR rate was 71.8% (28/39) and 56.4% (22/39), respectively, and the difference was statistically significant ( χ2 = 2.006, P = 0.157). Until the last follow up on September 19, 2020, 32 patients survived and 7 patients died in rhGM-CSF combined with R-CHOP regimen group, of which 1 case died of bowel cancer, and the primary disease was still in CR. In the R-CHOP regimen group, 32 survived and 7 died. The 2-year OS rates of the two groups were 82.5% and 73.9%, respectively ( χ2 = 0.038, P = 0.845); the 2-year PFS rates of the two groups were 67.1% and 55.2%, respectively ( χ2 = 0.457, P = 0.499). Subgroup analysis results showed that there were no statistically significant differences in CR rates among germinal center B-cell (GCB) and non-GCB subgroups, Lugano stage Ⅰ-Ⅱ and Lugano stage Ⅲ-Ⅳ subgroups, aged <60 years and aged ≥60 years subgroups in rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group (all P > 0.05). The major adverse reactions included bone marrow suppression and its inducible infections. There were no significant differences in the incidence of grade 3-4 hematological adverse reactions and infections between the two groups (all P > 0.05). All patients safely went through bone marrow suppression after support treatments without treatment-related deaths. Conclusions:rhGM-CSF combined with R-CHOP regimen is safe and effective in treatment of newly diagnosed DLBCL.