彌漫大B細(xì)胞淋巴瘤免疫組化標(biāo)記的預(yù)后意義及利妥昔單抗對(duì)其影響的臨床研究
發(fā)布時(shí)間：2019-05-23 07:03
【摘要】：目的:DLBCL患者在治療反應(yīng)以及預(yù)后具有顯著的生物學(xué)異質(zhì)性,不同的免疫亞型及ki-67、bcl-2的表達(dá)與預(yù)后有著密切的關(guān)系。隨著免疫治療藥物利妥昔單抗的應(yīng)用DLBCL生存得到明顯改善,因此上述基于傳統(tǒng)化療的預(yù)后指標(biāo)有待重新評(píng)價(jià)研究。本文旨在探討彌漫大B細(xì)胞淋巴瘤患者免疫學(xué)標(biāo)記及免疫學(xué)亞型的預(yù)后價(jià)值,以及利妥昔單抗對(duì)免疫組化標(biāo)記預(yù)后意義的影響。方法:回顧性分析新疆自治區(qū)人民醫(yī)院2005年1月-2013年12月收治的186例臨床資料和隨訪記錄完整的初治DLBCL患者病例資料,重新進(jìn)行國(guó)際預(yù)后指數(shù)評(píng)分,根據(jù)治療方案分為化療組(CHOP)及免疫化療組(RCHOP),所有患者都應(yīng)用免疫組織化學(xué)方法檢測(cè)CD45RO,CD3,CD5,CD20,CD79a,bcl-2,ki-67,bcl-6,CD10,MUM-1的表達(dá),并按hans分型方法將兩組患者分別分為GCB、non-GCB亞型,采用Kaplan-Meier法和Cox回歸模型,探討并比較bcl-6,CD10,MUM-1的表達(dá)以及免疫學(xué)亞型、bcl-2、ki-67、國(guó)際預(yù)后指數(shù)等指標(biāo)在兩組DLBCL患者的預(yù)后意義。結(jié)果:1.186例DLBCL患者化療組84例、免疫化療組102例,5年OS分別為42.86%、65.69%,二者差異有統(tǒng)計(jì)學(xué)意義(?2=7.111,P=0.008)。2.化療組中GCB型和non-GCB型的5年OS分別為58.82%和32.00%,差異有統(tǒng)計(jì)學(xué)意義(?2=8.482,P=0.004);免疫化療組中GCB型和non-GCB型的5年OS分別為72.97%和61.54%,差異無(wú)統(tǒng)計(jì)學(xué)意義(?2=2.694,P=0.101);進(jìn)一步分析顯示,non-GCB亞型中免疫化療組5年OS顯著優(yōu)于化療組(?2=7.385,P=0.007),但GCB亞型中兩種治療組5年OS差異無(wú)統(tǒng)計(jì)學(xué)意義(?2=1.304,P=0.253)。3.低危組107例,其中化療組47例,免疫化療組60例,進(jìn)一步分組,化療組中GCB型(19例)和non-GCB型(28例)5年OS分別為63.16%和46.43%,差異無(wú)統(tǒng)計(jì)學(xué)意義(?2=1.531,P=0.216),免疫化療組中GCB型(21例)和non-GCB型(39例)的5年OS分別為80.95%和74.36%,差異無(wú)統(tǒng)計(jì)學(xué)意義(?2=0.762,P=0.383);進(jìn)一步分析顯示,GCB及non-GCB亞型中化療與免疫化療組5年OS差異均無(wú)統(tǒng)計(jì)學(xué)意義(?2=0.867,P=0.352;?2=2.828,P=0.093)。高危組79例,其中化療組37例,免疫化療組42例,進(jìn)一步分組,化療組中GCB型(15例)和non-GCB型(22例)的5年OS分別為40.00%和22.72%,差異有統(tǒng)計(jì)學(xué)意義(?2=3.978,P=0.045),免疫化療組中GCB型(16例)和non-GCB型(26例)的5年OS分別為62.50%和42.31%,差異無(wú)統(tǒng)計(jì)學(xué)意義(?2=2.072,P=0.150);進(jìn)一步分析顯示,GCB及non-GCB亞型中化療組與免疫化療組5年OS差異均無(wú)統(tǒng)計(jì)學(xué)意義(?2=1.336,P=0.248;?2=1.873,P=0.171)。4.Cox多因素分析結(jié)果顯示,在化療組,ki-67≥60%(HR=0.910,95%CI=1.334-4.623,P=0.004)、IPI高危組(HR=0.669,95%CI=1.059-3.599,P=0.032),在免疫化療組,ki-67≥60%(HR=0.858,95%CI=1.078-4.521,P=0.030)、IPI高危組(HR=1.203,95%CI=1.609-6.889,P=0.001),兩組ki-67、國(guó)際預(yù)后指數(shù)評(píng)分均是獨(dú)立的預(yù)后因素。5.生存分析顯示,化療組non-GCB亞型中bcl-2陽(yáng)性組較bcl-2陰性組預(yù)后差,差異有統(tǒng)計(jì)學(xué)意義(P=0.025),而其它各亞組bcl-2陽(yáng)性組與bcl-2陰性組生存無(wú)差異。結(jié)論:1.免疫組化法將初治DLBCL分為兩種免疫亞型,對(duì)于早期判斷預(yù)后,指導(dǎo)治療具有一定的指導(dǎo)意義,在利妥昔單抗時(shí)代,免疫組化分型預(yù)后預(yù)測(cè)意義可能較以往有所降低。2.利妥昔單抗可顯著提高non-GCB型DLBCL患者的療效,但是對(duì)GCB型患者生存期的影響還需進(jìn)一步探討。3.DLBCL患者免疫學(xué)標(biāo)記具有一定的預(yù)后意義,無(wú)論在化療組、免疫化療組ki-67≥60%以及IPI高危組均是獨(dú)立的不良預(yù)后因素。而bcl-2聯(lián)合免疫學(xué)亞型對(duì)預(yù)后有一定提示意義。4.利妥昔單抗可改善DLBCL患者non-GCB亞型伴bcl-2陽(yáng)性患者預(yù)后。在non-GCB亞型,利妥昔單抗顯示出明顯的治療優(yōu)勢(shì),可能與該亞型bcl-2過(guò)表達(dá)有關(guān),進(jìn)一步提示利妥昔單抗可能克服bcl-2過(guò)表達(dá)的不良影響。
[Abstract]:Objective: The patients with DLBCL have significant biological heterogeneity, different immune subtypes and ki-67, and the expression of bcl-2 is closely related to the prognosis. With the improvement of the survival of the DLBCL with the application of rituximab, the above-mentioned prognostic indicators based on conventional chemotherapy have yet to be re-evaluated. The purpose of this study is to study the prognostic value of immunological markers and immunological subtypes in patients with diffuse large B-cell lymphoma, as well as the effect of rituximab on the prognostic significance of immunohistochemistry. Methods:186 clinical data and follow-up records from January 2005 to December 2013 of the People's Hospital of Xinjiang Autonomous Region were analyzed retrospectively. The expressions of CD45RO, CD3, CD5, CD20, CD79a, bcl-2, ki-67, bcl-6, CD10 and MUM-1 were detected by immunohistochemistry in all patients. The expression of MUM-1, as well as the immunological subtype, bcl-2, ki-67, and international prognostic index in the prognosis of two groups of DLBCL patients. Results: 1.186 patients with DLBCL in the chemotherapy group,102 cases of the immune chemotherapy group and 42.86% and 65.69% of the 5-year OS, respectively. 2=7.111,P=0.008).2. The 5-year OS of GCB and non-GCB in the chemotherapy group was 58.82% and 32.00%, respectively. 2 = 8.482, P = 0.004); the 5-year OS of GCB and non-GCB in the immune chemotherapy group was 72.97% and 61.54%, respectively, with no statistical significance (? 2 = 2.694, P = 0.101); further analysis showed that the 5-year OS in the non-GCB subtype was significantly superior to the chemotherapy group (? 2 = 7.385, P = 0.007), but there was no statistical significance for the 5-year OS difference between the two treatment groups in the GCB subtype (? 2=1.304,P=0.253).3. There were 107 cases of low-risk group, including 47 cases of chemotherapy group,60 cases of immune chemotherapy group, further group, GCB-type (19 cases) and non-GCB-type (28 cases)5-year OS in the chemotherapy group were 63.16% and 46.43%, respectively, and the difference was not significant (? 2 = 1.531, P = 0.216), the 5-year OS of GCB-type (21 cases) and non-GCB-type (39 cases) in the immune-chemotherapy group were 80.95% and 74.36%, respectively. 2 = 0.762, P = 0.383); further analysis showed no statistical significance for the 5-year OS difference in the GCB and non-GCB subtypes (? 2=0.867,P=0.352;? 2=2.828,P=0.093). 79 of the high-risk group, including 37 of the chemotherapy group,42 in the immune-chemotherapy group, the further group, the 5-year OS of the GCB-type (15 cases) and the non-GCB-type (22 cases) in the chemotherapy group were 40.00% and 22.72%, respectively, and the difference was statistically significant (? 2 = 3.978, P = 0.045), the 5-year OS of GCB-type (16 cases) and non-GCB-type (26 cases) in the immune chemotherapy group was 62.50% and 42.31%, respectively. 2 = 2.072, P = 0.150); further analysis showed that there was no statistical significance for the 5-year OS difference between the chemotherapy group and the non-GCB subtype in the GCB and non-GCB subtypes (? 2=1.336,P=0.248;? 2 = 1.873, P = 0.171).4. Cox multi-factor analysis showed that in the chemotherapy group, ki-67-60% (HR = 0.910,95% CI = 1.334-4.623, P = 0.004), IPI high-risk group (HR = 0.669,95% CI = 1.059-3.599, P = 0.032), in the immune-chemotherapy group, ki-67-60% (HR = 0.858,95% CI = 1.078-4.521, P = 0.030), IPI high-risk group (HR = 1.203,95% CI = 1.609-6.889, P = 0.001), and the two groups of ki-67 and international prognostic index scores were independent prognostic factors. The survival analysis showed that the bcl-2 positive group and the bcl-2 negative group in the non-GCB subtype of the chemotherapy group had poor prognosis, and there was no difference in the survival of the bcl-2 positive group and the bcl-2 negative group in the other subgroups (P = 0.025). Conclusion:1. The first treatment of DLBCL was divided into two types of immunophenotyping. Rituximab can significantly improve the efficacy of non-GCB-type DLBCL patients, but it is necessary to further explore the effect of rituximab on the survival of patients with GCB type.3. The immunological markers of DLBCL patients have a certain prognostic significance, no matter in the chemotherapy group, The group of immunochemotherapy group ki-67-60% and the high-risk group of IPI were independent poor prognosis factors. The co-immunological subtype of bcl-2 has a certain significance for prognosis. Rituximab can improve the prognosis of non-GCB subtype with bcl-2 positive patients in the patients with DLBCL. In the non-GCB subtype, rituximab shows a significant therapeutic advantage and may be related to the overexpression of the subtype of bcl-2, further suggesting that rituximab may overcome the negative effects of the overexpression of bcl-2.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R733.1
本文編號(hào)：2483699
[Abstract]:Objective: The patients with DLBCL have significant biological heterogeneity, different immune subtypes and ki-67, and the expression of bcl-2 is closely related to the prognosis. With the improvement of the survival of the DLBCL with the application of rituximab, the above-mentioned prognostic indicators based on conventional chemotherapy have yet to be re-evaluated. The purpose of this study is to study the prognostic value of immunological markers and immunological subtypes in patients with diffuse large B-cell lymphoma, as well as the effect of rituximab on the prognostic significance of immunohistochemistry. Methods:186 clinical data and follow-up records from January 2005 to December 2013 of the People's Hospital of Xinjiang Autonomous Region were analyzed retrospectively. The expressions of CD45RO, CD3, CD5, CD20, CD79a, bcl-2, ki-67, bcl-6, CD10 and MUM-1 were detected by immunohistochemistry in all patients. The expression of MUM-1, as well as the immunological subtype, bcl-2, ki-67, and international prognostic index in the prognosis of two groups of DLBCL patients. Results: 1.186 patients with DLBCL in the chemotherapy group,102 cases of the immune chemotherapy group and 42.86% and 65.69% of the 5-year OS, respectively. 2=7.111,P=0.008).2. The 5-year OS of GCB and non-GCB in the chemotherapy group was 58.82% and 32.00%, respectively. 2 = 8.482, P = 0.004); the 5-year OS of GCB and non-GCB in the immune chemotherapy group was 72.97% and 61.54%, respectively, with no statistical significance (? 2 = 2.694, P = 0.101); further analysis showed that the 5-year OS in the non-GCB subtype was significantly superior to the chemotherapy group (? 2 = 7.385, P = 0.007), but there was no statistical significance for the 5-year OS difference between the two treatment groups in the GCB subtype (? 2=1.304,P=0.253).3. There were 107 cases of low-risk group, including 47 cases of chemotherapy group,60 cases of immune chemotherapy group, further group, GCB-type (19 cases) and non-GCB-type (28 cases)5-year OS in the chemotherapy group were 63.16% and 46.43%, respectively, and the difference was not significant (? 2 = 1.531, P = 0.216), the 5-year OS of GCB-type (21 cases) and non-GCB-type (39 cases) in the immune-chemotherapy group were 80.95% and 74.36%, respectively. 2 = 0.762, P = 0.383); further analysis showed no statistical significance for the 5-year OS difference in the GCB and non-GCB subtypes (? 2=0.867,P=0.352;? 2=2.828,P=0.093). 79 of the high-risk group, including 37 of the chemotherapy group,42 in the immune-chemotherapy group, the further group, the 5-year OS of the GCB-type (15 cases) and the non-GCB-type (22 cases) in the chemotherapy group were 40.00% and 22.72%, respectively, and the difference was statistically significant (? 2 = 3.978, P = 0.045), the 5-year OS of GCB-type (16 cases) and non-GCB-type (26 cases) in the immune chemotherapy group was 62.50% and 42.31%, respectively. 2 = 2.072, P = 0.150); further analysis showed that there was no statistical significance for the 5-year OS difference between the chemotherapy group and the non-GCB subtype in the GCB and non-GCB subtypes (? 2=1.336,P=0.248;? 2 = 1.873, P = 0.171).4. Cox multi-factor analysis showed that in the chemotherapy group, ki-67-60% (HR = 0.910,95% CI = 1.334-4.623, P = 0.004), IPI high-risk group (HR = 0.669,95% CI = 1.059-3.599, P = 0.032), in the immune-chemotherapy group, ki-67-60% (HR = 0.858,95% CI = 1.078-4.521, P = 0.030), IPI high-risk group (HR = 1.203,95% CI = 1.609-6.889, P = 0.001), and the two groups of ki-67 and international prognostic index scores were independent prognostic factors. The survival analysis showed that the bcl-2 positive group and the bcl-2 negative group in the non-GCB subtype of the chemotherapy group had poor prognosis, and there was no difference in the survival of the bcl-2 positive group and the bcl-2 negative group in the other subgroups (P = 0.025). Conclusion:1. The first treatment of DLBCL was divided into two types of immunophenotyping. Rituximab can significantly improve the efficacy of non-GCB-type DLBCL patients, but it is necessary to further explore the effect of rituximab on the survival of patients with GCB type.3. The immunological markers of DLBCL patients have a certain prognostic significance, no matter in the chemotherapy group, The group of immunochemotherapy group ki-67-60% and the high-risk group of IPI were independent poor prognosis factors. The co-immunological subtype of bcl-2 has a certain significance for prognosis. Rituximab can improve the prognosis of non-GCB subtype with bcl-2 positive patients in the patients with DLBCL. In the non-GCB subtype, rituximab shows a significant therapeutic advantage and may be related to the overexpression of the subtype of bcl-2, further suggesting that rituximab may overcome the negative effects of the overexpression of bcl-2.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R733.1
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 周穎;趙瑜;薄劍;李艷芬;馬超;石亞男;;Ki-67在彌漫大B細(xì)胞淋巴瘤中的表達(dá)及臨床意義[J];中國(guó)實(shí)驗(yàn)血液學(xué)雜志;2013年05期
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