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人粒细胞-巨噬细胞集落刺激因子联合R-CHOP方案治疗弥漫大B细胞淋巴瘤的临床疗效研究

Clinical curative effect of rhGM -CSF joint R -CHOP regimen in the treatment of diffuse large B cell lymphoma

摘要目的:探讨人粒细胞-巨噬细胞集落刺激因子( rhGM-CSF)联合R-CHOP方案治疗弥漫大B细胞淋巴瘤的临床疗效。方法选取2014年1月至2015年1月住院治疗的弥漫大B细胞淋巴瘤( DLBCL)患者72例,采用数字表法将患者随机分为利妥昔单抗联合CHOP组( R-CHOP组,36例)和联合组(36例), R-CHOP组采用R-CHOP方案治疗,联合组在R-CHOP的基础上加用rhGM-CSF治疗。在化疗前、化疗开始后第15天,化疗后1、3个月采集两组患者外周血,分离单核细胞,使用流式细胞仪计数HLA-DR、CD197标记的M1和CD68、CDl63标记的M2,于化疗后4个月对患者进行疗效评价,记录不良反应情况。结果两组治疗后4个月,联合组客观有效率(ORR,91.67%)显著高于R-CHOP组(ORR,75.00%),两组差异有统计学意义(χ2=4.372,P<0.05);联合组治疗后不良反应中,肝功能损伤Ⅰ~Ⅱ级8.33%,Ⅲ~Ⅳ级0.00%;白细胞降低Ⅰ~Ⅱ级25.00%,Ⅲ~Ⅳ级5.56%;血小板减少Ⅰ~Ⅱ级19.44%,Ⅲ~Ⅳ级8.33%;恶心呕吐Ⅰ~Ⅱ级8.33%,Ⅲ~Ⅳ级0.00%。 R-CHOP组治疗后不良反应中,肝功能损伤Ⅰ~Ⅱ级13.89%,Ⅲ~Ⅳ级2.78%;白细胞降低Ⅰ~Ⅱ级36.11%,Ⅲ~Ⅳ级11.11%;血小板减少Ⅰ~Ⅱ级33.33%,Ⅲ~Ⅳ级2.78%;恶心呕吐Ⅰ~Ⅱ级13.89%,Ⅲ~Ⅳ级0.00%。联合组治疗后TAM数量增加例数比率(63.89%)显著多于R-CHOP组(38.89%),差异有统计学意义(χ2=7.938,P <0.05);联合组 CD68(46.11%)、IL-6(44.44%)、IL-8(58.33%)的阳性表达率显著高于R-CHOP组CD68(13.89%)、IL-6(19.44%)、IL-8(38.89%),差异均有统计学意义(χ2=3.278、4.021、4.489,均P<0.05)。结论 R-CHOP联合rhGM-CSF较单纯R-CHOP方案临床疗效更加显著,不良反应更少,且在rhGM-CSF诱导下,单核细胞可发育成M1型巨噬细胞,在DLBCL微环境下,可诱导M2型TAM向M1型发生逆向极化,改善DLBCL的微环境,为DLBCL的治愈提供可能的机会。

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abstractsObjective To study the clinical curative effect of the recombinant human granulocyte-macro-phage colony-stimulating factor ( rhGM -CSF) joint R-CHOP regimen in the treatment of diffuse large B cell lymphoma (DLBCL).Methods 72 hospitalized patients with DLBCL were chosen from January 2014 to January 2015.The patients were randomly divided into joint CHOP rituxan group ( R-CHOP group,36 cases) and the joint treatment group (36 cases) .The R-CHOP group was treated by R-CHOP regimen,the joint group was given rhGM-CSF on the basis of R-CHOP treatment.Before chemotherapy and 15 days,1 month,3 months after chemotherapy, the peripheral blood was collected,and the monocytes were separated,flow cytometry was used to count HLA-DR, CD197 marked M1 cells and CD68,CDl63 marked M2 cells.4 months after chemotherapy,the curative effect was evaluated.Results 4 months after treatment,the ORR of joint group (91.67%) was significantly higher than that of R-CHOP group (75.00%),and the difference was statistically significant (χ2 =4.372,P<0.05).After treatment, the adverse reactions of joint group,the liver function injuryⅠ-Ⅱlevel 8.33%,Ⅲ-Ⅳlevel 0.00%;White blood cells reduceⅠ-Ⅱlevel 25.00%,Ⅲ-Ⅳ level 5.56%;Thrombocytopenia Ⅰ-Ⅱ level 19.44%,Ⅲ-Ⅳ level;8.33%;Nausea and vomitingⅠ-Ⅱ level 8.33%,Ⅲ-Ⅳ level 0.00%.The adverse reactions after treatment of&nbsp;R-CHOP group,the liver function injury Ⅰ-Ⅱ level 13.89%,grade Ⅲ-Ⅳ2.78%;White blood cells reduceⅠ-Ⅱlevel 36.11%,Ⅲ-Ⅳlevel 11.11%;ThrombocytopeniaⅠ-Ⅱlevel 33.33%,Ⅲ-Ⅳlevel 2.78%;Nau-sea and vomitingⅠ-Ⅱ level 13.89%,Ⅲ-Ⅳ level 0.00%.The increased ratio of TAM quantity in combined treatment group (63.89%) was significantly more than R-CHOP group (38.89%),the difference was statistically significant (χ2 =7.938,P <0.05).In joint group,the positive expression rates of CD68 (46.11%),IL -6 (44.44%),IL-8 (58.33%) were significantly higher than those of R-CHOP group[CD68 (13.89%),IL-6 (19.44%),IL-8 (38.89%)],the differences were statistically significant (χ2 =3.278,3.278,4.489,all P<0.05).Conclusion R-CHOP joint rhGM -CSF has better curative effect than R-CHOP plan and less adverse reaction,and under the induction of rhGM -CSF,mononuclear cells can develop into M1 macrophages,in DLBCL microenvironment,to induce TAM to M1 M2 type in reverse polarization,improve the microenvironment of DLBCL and provide chance for cure of DLBCL.

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