硼替佐米对多发性骨髓瘤患者免疫功能、炎症反应及肾功能的影响
|
摘要
目的:本研究主要对比硼替佐米和长春新碱联合地塞米松、沙利度胺对多发性骨髓瘤患者免疫功能、机体炎症反应、肾功能、骨髓瘤细胞及M蛋白的影响。方法:选取在我院接受治疗的68例多发性骨髓瘤患者,根据化疗使用的药物分为对照组和观察组,对照组给予长春新碱联合地塞米松与沙利度胺治疗,观察组给予硼替佐米联合地塞米松与沙利度胺治疗。检测两组治疗前后免疫细胞(CD3~+、CD4~+、CD4~+/CD8~+、Treg)、炎症因子(CRP、TNF-α)、肾功能(SCr、BUN)、骨髓瘤细胞及M蛋白等生化指标。结果:观察组化疗后CD3~+、CD4~+、CD4~+/CD8~+、Treg明显优于对照组,两组比较差异具有统计学意义(P<0.05);观察组炎症因子CRP、TNF-α水平显著降低,差异具有统计学意义(P<0.05);观察组骨髓瘤细胞、M蛋白水平明显低于对照组,肾功能SCr、BUN改善程度显著优于对照组,差异均具有统计学意义(P<0.05)。结论:硼替佐米联合地塞米松和沙利度胺化疗方案可有效降低多发性骨髓瘤患者炎症反应、M蛋白及骨髓瘤细胞,改善患者机体免疫功能及肾功能,具有一定的临床推广应用价值。
Objective: In this study, the effects of bortezomib and vincristine combined with dexamethasone and thalidomide on immune function, inflammatory response, renal function, myeloma cells and plasma cells in patients with multiple myeloma were compared. Methods: 68 patients with multiple myeloma treated in our hospital from May 2009 to Nov. 2018 were selected and divided into control group and observation group according to the drugs used in chemotherapy. The control group was treated with vincristine combined with dexamethasone and thalidomide, while the observation group was treated with bortezomib combined with dexamethasone and thalidomide.Immunocytes, inflammatory cytokines, serum creatinine, blood urea nitrogen, myeloma cells and plasma cells were detected before and after treatment in the two groups. Results: There was no significant difference in each index between the two groups before treatment(P>0.05). After three courses of chemotherapy, CD3~+, CD4~+, CD4~+/CD8~+ and Treg in the observation group were significantly better than those in the control group, and the difference between the two groups was statistically significant(P<0.05). The levels of inflammatory cytokines CRP, TNF-α, myeloma cells and M protein were significantly decreased in the observation group(P<0.05). Renal function indexes in the observation group were significantly higher than those in the control group(P<0.05). There was no significant difference in clinical efficacy and adverse reactions between the two groups(P<0.05). Conclusion:Bortezomib combined with dexamethasone and thalidomide can effectively reduce the inflammatory response, M protein and myeloma cells in patients with MM, significantly improve the immune function and renal function in patients, which has certain clinical application value.
Objective: In this study, the effects of bortezomib and vincristine combined with dexamethasone and thalidomide on immune function, inflammatory response, renal function, myeloma cells and plasma cells in patients with multiple myeloma were compared. Methods: 68 patients with multiple myeloma treated in our hospital from May 2009 to Nov. 2018 were selected and divided into control group and observation group according to the drugs used in chemotherapy. The control group was treated with vincristine combined with dexamethasone and thalidomide, while the observation group was treated with bortezomib combined with dexamethasone and thalidomide.Immunocytes, inflammatory cytokines, serum creatinine, blood urea nitrogen, myeloma cells and plasma cells were detected before and after treatment in the two groups. Results: There was no significant difference in each index between the two groups before treatment(P>0.05). After three courses of chemotherapy, CD3~+, CD4~+, CD4~+/CD8~+ and Treg in the observation group were significantly better than those in the control group, and the difference between the two groups was statistically significant(P<0.05). The levels of inflammatory cytokines CRP, TNF-α, myeloma cells and M protein were significantly decreased in the observation group(P<0.05). Renal function indexes in the observation group were significantly higher than those in the control group(P<0.05). There was no significant difference in clinical efficacy and adverse reactions between the two groups(P<0.05). Conclusion:Bortezomib combined with dexamethasone and thalidomide can effectively reduce the inflammatory response, M protein and myeloma cells in patients with MM, significantly improve the immune function and renal function in patients, which has certain clinical application value.
引文
1 Crowley MP,Quinn S,Coleman E,et al.Erratum to:Differing coagulation profiles of patients with monoclonal gammopathy of undetermined significance and multiple myeloma[J].J Thromb Thrombolysis,2015,39(2):250.
2 施玲玲,翟勇平.多发性骨髓瘤细胞对硼替佐米耐药机制的研究进展[J].中国实验血液学杂志,2017,25(5):1576-1579.
3 陈佳文,艾绍正,白海,等.蛋白酶体抑制剂治疗多发性骨髓瘤的研究进展[J].国际输血及血液学杂志,2017,40(6):517-521.
4 Kumar SK,Callander NS,Alsina M,et al.Multiple myeloma,version 3.2017,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2017,15(2):230-269.
5 Mohan M,Matin A,Davies FE.Update on the optimal use of bortezomib in the treatment of multiple myeloma[J].Cancer Manag Res,2017,9:51-63.
6 Wu YX,Yang JH,Saitsu H.Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance[J].Oncotarget,2016,7(47):77622-77634.
7 江苏省抗癌协会血液肿瘤专业委员会.《中国多发性骨髓瘤诊治指南(2015年修订)》治疗部分江苏解读[J].医学研究生学报,2016,29(10):1014-1019.
8 中国医师协会血液科医师分会,中华医学会血液学分会,中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南(2015年修订)[J].中华内科杂志,2015,54(12):1066-1070.
9 Dimopoulos MA,Richardson PG,Moreau P,et al.Current treatment landscape for relapsed and/or refractory multiple myeloma[J].Nat Rev Clin Oncol,2015,12(1):42-54.
10 Avet-Loiseau H,Bahlis NJ,Chng WJ,et al.Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients[J].Blood,2017,130(24):2610-2618.
11 Bersani-Amado LE,Dantas JA,Dami?o MJ,et al.Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice:effects of thalidomide and dexamethasone[J].Fundam Clin Pharmacol,2016,30(1):35-46.
12 Terpos E,Morgan G,Dimopoulos MA,et al.International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease[J].J Clin Oncol,2013,31(18):2347-2357.
13 Hashimoto S,Kuroha T,Yano T,et al.The addition of low-dose thalidomide to bortezomib and dexamethasone for refractory multiple myeloma[J].Intern Med,2016,55(20):3025-3028.
14 Sonneveld P,Schmidt-Wolf IG,vander Holt B,et al.Bortezomibinduction and maintenance treatment in patients with newly diagnosed multiple myeloma:results of the randomized phase III HOVON-65/ GMMG-HD4 trial[J].J Clin Oncol,2012,30(24):2946-2955.
15 Guillerey C,Nakamura K,Vuckovic S,et al.Immune responses in multiple myeloma:role of the natural immune surveillance and potential of immunotherapies[J].Cell Mol Life Sci,2016,73(8):1569-1589.
16 Ray A,Das DS,Song Y,et al.Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells,natural killer cells and multiple myeloma cells[J].Leukemia,2015,29(6):1441-1444.
17 G?rgün G,SamurMK,CowensKB,et al.Lenalidomideenhances immune checkpoint blockade-induced immune response in multiple myeloma[J].Clin Cancer Res,2015,21(20):4607-4618.
18 Zhang X,Wu XC,Xiong L,et al.Role of vitamin D3 in regulation of T helper cell 17 and regulatory T-cell balance in rats with immunoglobulin a nephropathy[J].Iran J Kidney Dis,2014,8(5):363-370.
19 宋丽丽.不同化疗方案对多发性骨髓瘤患者T细胞亚群及相关细胞因子的影响[D].苏州:苏州大学,2016.
20 段俊虎.沙利度胺治疗多发性骨髓瘤的疗效及对血清相关指标的影响[J].实用癌症杂志,2015,30(2):295-297,300.
2 施玲玲,翟勇平.多发性骨髓瘤细胞对硼替佐米耐药机制的研究进展[J].中国实验血液学杂志,2017,25(5):1576-1579.
3 陈佳文,艾绍正,白海,等.蛋白酶体抑制剂治疗多发性骨髓瘤的研究进展[J].国际输血及血液学杂志,2017,40(6):517-521.
4 Kumar SK,Callander NS,Alsina M,et al.Multiple myeloma,version 3.2017,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2017,15(2):230-269.
5 Mohan M,Matin A,Davies FE.Update on the optimal use of bortezomib in the treatment of multiple myeloma[J].Cancer Manag Res,2017,9:51-63.
6 Wu YX,Yang JH,Saitsu H.Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance[J].Oncotarget,2016,7(47):77622-77634.
7 江苏省抗癌协会血液肿瘤专业委员会.《中国多发性骨髓瘤诊治指南(2015年修订)》治疗部分江苏解读[J].医学研究生学报,2016,29(10):1014-1019.
8 中国医师协会血液科医师分会,中华医学会血液学分会,中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南(2015年修订)[J].中华内科杂志,2015,54(12):1066-1070.
9 Dimopoulos MA,Richardson PG,Moreau P,et al.Current treatment landscape for relapsed and/or refractory multiple myeloma[J].Nat Rev Clin Oncol,2015,12(1):42-54.
10 Avet-Loiseau H,Bahlis NJ,Chng WJ,et al.Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients[J].Blood,2017,130(24):2610-2618.
11 Bersani-Amado LE,Dantas JA,Dami?o MJ,et al.Involvement of cytokines in the modulation and progression of renal fibrosis induced by unilateral ureteral obstruction in C57BL/6 mice:effects of thalidomide and dexamethasone[J].Fundam Clin Pharmacol,2016,30(1):35-46.
12 Terpos E,Morgan G,Dimopoulos MA,et al.International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease[J].J Clin Oncol,2013,31(18):2347-2357.
13 Hashimoto S,Kuroha T,Yano T,et al.The addition of low-dose thalidomide to bortezomib and dexamethasone for refractory multiple myeloma[J].Intern Med,2016,55(20):3025-3028.
14 Sonneveld P,Schmidt-Wolf IG,vander Holt B,et al.Bortezomibinduction and maintenance treatment in patients with newly diagnosed multiple myeloma:results of the randomized phase III HOVON-65/ GMMG-HD4 trial[J].J Clin Oncol,2012,30(24):2946-2955.
15 Guillerey C,Nakamura K,Vuckovic S,et al.Immune responses in multiple myeloma:role of the natural immune surveillance and potential of immunotherapies[J].Cell Mol Life Sci,2016,73(8):1569-1589.
16 Ray A,Das DS,Song Y,et al.Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells,natural killer cells and multiple myeloma cells[J].Leukemia,2015,29(6):1441-1444.
17 G?rgün G,SamurMK,CowensKB,et al.Lenalidomideenhances immune checkpoint blockade-induced immune response in multiple myeloma[J].Clin Cancer Res,2015,21(20):4607-4618.
18 Zhang X,Wu XC,Xiong L,et al.Role of vitamin D3 in regulation of T helper cell 17 and regulatory T-cell balance in rats with immunoglobulin a nephropathy[J].Iran J Kidney Dis,2014,8(5):363-370.
19 宋丽丽.不同化疗方案对多发性骨髓瘤患者T细胞亚群及相关细胞因子的影响[D].苏州:苏州大学,2016.
20 段俊虎.沙利度胺治疗多发性骨髓瘤的疗效及对血清相关指标的影响[J].实用癌症杂志,2015,30(2):295-297,300.