本文選題：真實(shí)世界 + 多發(fā)性骨髓瘤��； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:研究真實(shí)世界中,含硼替佐米方案與不含硼替佐米方案治療多發(fā)性骨髓瘤療效差異與安全性評估異同,同時(shí)分析多發(fā)性骨髓瘤病人的OS與PFS及其與硼替佐米累積劑量的關(guān)系,并討論早期死亡和影響預(yù)后的可能因素。方法:選取2012年1月1日至2015年12月2日就診于河北醫(yī)科大學(xué)第三醫(yī)院血液科初診為多發(fā)性骨髓瘤(multiple myeloma,MM)的108例病人做為研究對象,按化療治療方案分為含硼替佐米組與不含硼替佐米組。含硼替佐米組37例病人,不含硼替佐米組71例病人,隨訪截止至2016年1月1日。硼替佐米組男性比例較高(73%vs48%,P=0.013),兩方案組病人年齡、隨訪時(shí)間、MM分型、DS分期、ISS分期的差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)果:1硼替佐米組與非硼替佐米組療效比較1.1硼替佐米組10例CR(27%),10例VGPR(27%),10例PR(27%),ORR達(dá)到81.1%;隨訪期間9例復(fù)發(fā),其中1例2次復(fù)發(fā);共死亡7例(6例為6個(gè)月內(nèi)早期死亡);1.2非硼替佐米組12例CR(16.9%),9例VGPR(12.7%),29例PR(40.8%),ORR達(dá)到70.4%;隨訪期間36例復(fù)發(fā),其中7例2次復(fù)發(fā),1例3次復(fù)發(fā);共死亡17例(3例為6個(gè)月內(nèi)早期死亡);1.3兩方案組療效比較硼替佐米組總有效率ORR高于非硼替佐米組(81.1%對70.4%,P=0.230)且≥VGPR率高于非硼替佐米組(54.1%vs29.6%,P=0.013),但并未發(fā)現(xiàn)年齡因素對療效的影響;1.4兩方案組達(dá)最佳療效(≥PR)所需療程硼替佐米組中位2程,平均1.68程,1-4程;非硼替佐米組中位4程,平均4.2程,1-7程;療程數(shù)比較p0.001;2緩解深度與pfs、os的關(guān)系兩方案組刪失率均小于70%,可行pfs生存分析;兩方案組刪失率均大于70%,中位os未達(dá)到;2.1硼替佐米組療效達(dá)≥vgpr(中位pfs23個(gè)月)vsvgpr(中位pfs6個(gè)月),p=0.022;療效達(dá)≥pr(中位pfs23個(gè)月)vspr(中位pfs2個(gè)月),p0.001,差異均有統(tǒng)計(jì)學(xué)意義;2.2非硼替佐米組療效達(dá)≥vgpr(中位pfs24個(gè)月)vsvgpr(中位pfs12個(gè)月),p0.05,差異有統(tǒng)計(jì)學(xué)意義;療效達(dá)≥pr(中位pfs17個(gè)月)vspr(中位pfs9個(gè)月),p=0.141,差異無統(tǒng)計(jì)學(xué)意義;2.3總體療效達(dá)≥vgpr(中位pfs23個(gè)月)vsvgpr(中位pfs12個(gè)月),p0.05;療效達(dá)≥pr(中位pfs18個(gè)月)vspr(中位pfs6個(gè)月),p0.005,差異均有統(tǒng)計(jì)學(xué)意義;3誘導(dǎo)及鞏固治療階段硼替佐米累積量與pfs的關(guān)系硼替佐米中位累積劑量為15.6mg/m2。采用k-m(kaplanmeier)法繪制生存曲線,≥15.6mg/m2(17例)組pfs23個(gè)月與15.6mg/m2(20例)組pfs10個(gè)月,p=0.019;4mm病人pfs生存分析單因素分析結(jié)果示是否合并冠心病、是否進(jìn)展為漿細(xì)胞白血病、初診是否plt減少、初診是否低白蛋白血癥、初診是否ldh250u/l的檢驗(yàn)均p0.05,差異有統(tǒng)計(jì)學(xué)意義。將年齡(p=0.224)、方案分組(p=0.590)、issⅢ期(p=0.090)一同代入多因素分析,結(jié)果示應(yīng)用硼替佐米為pfs保護(hù)因素,issⅢ期、年齡≥65歲、進(jìn)展為漿細(xì)胞白血病、初診低白蛋白血癥、初診ldh250u/l均為pfs危險(xiǎn)因素,含硼替佐米組中位pfs比不含硼替佐米組約長10個(gè)月(23個(gè)月vs12個(gè)月,p=0.019);5mm病人早期死亡獨(dú)立危險(xiǎn)因素分析108例病人共有9例早期死亡,含硼替佐米組6例,不含硼替佐米組3例,單因素分析結(jié)果示方案分組(P=0.046)、是否合并冠心病(P=0.001)、是否PLT減少(P=0.017)、初診是否LDH250 U/L(P=0.001)與早期死亡相關(guān);多因素Logistic回歸分析得出只有初診LDH250 U/L(P=0.025,OR 0.157,95%CI 0.031-0.789)及合并冠心病(P=0.016,OR0.136,95%CI 0.027-0.686)為MM病人早期死亡獨(dú)立危險(xiǎn)因素;6化療安全性評估評估顯示,不含B組化療后出現(xiàn)中性粒細(xì)胞減少(P=0.001)、貧血(P=0.001)及電解質(zhì)紊亂(P0.001)的不良反應(yīng)發(fā)生頻率高,含B組化療后出現(xiàn)PLT減少(P=0.006)的不良反應(yīng)發(fā)生頻率高。結(jié)論:1含硼替佐米方案組療效優(yōu)于不含硼替佐米方案,且達(dá)≥PR所需療程短,反應(yīng)速率快;2含硼替佐米方案療效達(dá)PR可使病人PFS獲益,而非硼替佐米組須達(dá)VGPR以上;3高累積劑量硼替佐米可延長MM病人的PFS;4含硼替佐米組中位PFS高出不含硼替佐米組約10個(gè)月(23個(gè)月VS12個(gè)月,P=0.019),而ISSⅢ期、年齡≥65歲、進(jìn)展為漿細(xì)胞白血病、初診低白蛋白血癥、初診LDH250 U/L均為PFS的危險(xiǎn)因素;中位OS未達(dá)到;5初診LDH250 U/L及合并冠狀動脈粥樣硬化性心臟病為MM病人早期死亡獨(dú)立危險(xiǎn)因素,硼替佐米不能降低早期死亡率;6含硼替佐米方案化療后更易出現(xiàn)PLT減少,不含硼替佐米方案化療后更易出現(xiàn)中性粒細(xì)胞減少、貧血及電解質(zhì)紊亂;7本研究存在樣本量偏少及單中心病員選擇等限制,所得出結(jié)論未必全面,更好更有意義的結(jié)果需要擴(kuò)大樣本量及多中心合作來實(shí)現(xiàn)。
[Abstract]:Objective: To study the difference of efficacy and safety assessment between bortezomizomi scheme and bortezomizomi regimen in the real world in the treatment of multiple myeloma, and to analyze the relationship between OS and PFS and the cumulative dose of bortezomib in patients with multiple myeloma, and discuss the possible factors affecting early death and prognosis. Methods: 2012 From January 1st to December 2, 2015, 108 patients who were diagnosed as multiple myeloma (MM) in the Department of Hematology, Third Hospital of Hebei Medical University, were divided into bortezomizomi group and bortezomizomi group. 37 patients with bortezomizomi group and 71 patients without bortezomizomi group were followed up. By January 1, 2016, the male proportion of bortezomizomi group was higher (73%vs48%, P=0.013). There was no significant difference in age, follow-up time, MM typing, DS staging and ISS staging in two regimen group (P0.05). Results: 1 bortezomizomi group and non bortezomizomi group were more effective than 1.1 bortezomizomi group, 10 cases, CR (27%), 10 VGPR (27%), 10 PR (27%), ORR. Up to 81.1%, 9 cases relapsed during the follow-up period, of which 1 cases had 2 recurrence, and 7 cases died (6 cases were early death in 6 months); 1.2 non bortezomizo group 12 cases CR (16.9%), 9 cases (12.7%), 29 cases PR (40.8%) and ORR recurrence. The total effective rate of bortezomizomi group was higher than that of bortezomizomi group (81.1% to 70.4%, P=0.230) and the rate of VGPR was higher than that of non bortezomizomi group (54.1%vs29.6%, P=0.013), but the effect was not found by age factors; 1.4 two regimen group reached the best therapeutic effect (> PR) in the middle 2 course of the bortezomizomizomizomi group, the average 1.68 course, 1-4 course. The median 4 course of the non bortezomizo group, average 4.2 course, 1-7 course, p0.001, 2 remission depth and PFS, OS, the deletion rate of the two scheme group was less than 70%, the feasible PFS survival analysis; the two scheme group was more than 70%, the median OS was not reached; 2.1. The effect of bortezomizomi group was greater than vgpr (median pfs23 months) vsvgpr (median pfs6 month), p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; therapy Pr (median pfs23 months) vspr (median pfs2 months), p0.001, the difference was statistically significant; 2.2 the effect of non bortezomizomi group was greater than vgpr (median pfs24 months) vsvgpr (median pfs12 month), P0.05, the difference was statistically significant; the curative effect reached > pr (median pfs17 month), the difference was not statistically significant; the 2.3 population was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; 2.2 The curative effect was more than vgpr (median pfs23 months) vsvgpr (median pfs12 months) and P0.05; the curative effect was greater than pr (median pfs18 months) vspr (median pfs6 months), P0.005, and the difference was statistically significant; 3 the cumulative dose of bortezomizomizomi and PFS were induced and consolidated at the stage of treatment. The survival curve, 15.6mg/m2 (17 cases) (20 cases) and 15.6mg/m2 (20 cases) group pfs10 months, p=0.019; 4mm patients PFS survival analysis single factor analysis results showed whether the combination of coronary heart disease, whether progression to plasma cell leukemia, first diagnosis of PLT reduction, first diagnosis of hypoalbuminemia, the first diagnosis of ldh250u/l is P0.05, the difference is statistically significant P0.05, the difference is statistically significant Age (p=0.224), scheme grouping (p=0.590) and ISS III (p=0.090) were combined into multiple factors analysis. The results showed that bortezomib was a PFS protective factor, ISS III, age more than 65 years old, progressing to plasma cell leukemia, early diagnosis of hypoalbuminemia, and primary diagnosis of ldh250u/l as a risk factor for PFS, and the median PFS ratio in the bortezomizomi group was not borosilia. The Zomi group was about 10 months (23 months vs12 months, p=0.019); the independent risk factors for early death of 5mm patients were analyzed in 108 patients with 9 early deaths, 6 cases of bortezomizomi group and 3 cases without bortezomizomi group. The single factor analysis showed the scheme grouping (P=0.046), whether or not coronary heart disease (P=0.001), PLT decrease (P=0.017), and first diagnosis of LDH2 50 U/L (P=0.001) was associated with early death; multiple factor Logistic regression analysis showed that only primary LDH250 U/L (P=0.025, OR 0.157,95%CI 0.031-0.789) and combined coronary artery disease (P=0.016, OR0.136,95%CI 0.027-0.686) were independent risk factors for early death. 6 chemotherapy safety assessment assessment showed no neutrophils after chemotherapy. Cytosolic (P=0.001), anemia (P=0.001) and electrolyte disorder (P0.001) have a high frequency of adverse reactions, and the adverse reaction of PLT reduction (P=0.006) in the group B after chemotherapy is high. Conclusion: 1, bortezomizomi regimen is better than bortezomib without bortezomizomi scheme, and the treatment course is shorter and the rate of reaction is faster than that of the group of borosomizomizomi, and 2 the treatment of bortezomizomi scheme. PR could benefit the patient's PFS, while the non bortezomizomi group was more than VGPR; 3 the high cumulative dose of bortezomib could prolong the PFS of the patients with MM; 4 the median bortezomizomi group was higher than the bortezomizomi group for about 10 months (23 months VS12, P=0.019), and the ISS III, the age of more than 65 years, was progressing to plasma cell leukemia, first diagnosis of hypoalbuminemia. LDH250 U/L was a risk factor for PFS; median OS was not reached; 5 first diagnosis of LDH250 U/L and coronary atherosclerotic heart disease were independent risk factors for early death of MM patients. Bortezomizomi could not reduce early mortality; 6 the bortezomizomi regimen was more susceptible to PLT reduction after chemotherapy, and no bortezomizomi regimen was more likely to occur after chemotherapy. Neutrophils, anemia and electrolyte disorders; 7 there are limited samples and choice of single center patients. The results are not necessarily comprehensive, and better and more meaningful results need to be achieved by expanding the sample size and multi center cooperation.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.3

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