《彌漫大B細(xì)胞淋巴瘤(DLBCL)過去現(xiàn)在和將來——瑞金醫(yī)院血液科沈志祥》由會(huì)員分享，可在線閱讀，更多相關(guān)《彌漫大B細(xì)胞淋巴瘤(DLBCL)過去現(xiàn)在和將來——瑞金醫(yī)院血液科沈志祥（47頁珍藏版）》請(qǐng)?jiān)谘b配圖網(wǎng)上搜索。

1、單擊此處編輯母版標(biāo)題樣式,單擊此處編輯母版文本樣式,第二級(jí),第三級(jí),第四級(jí),第五級(jí),*,*,彌漫大,B,細(xì)胞淋巴瘤,(DLBCL),過去現(xiàn)在和將來,上海瑞金醫(yī)院,沈志祥,東方和西方淋巴瘤的發(fā)病率,B-indolent,B-aggressive,T-cell,West,East,Nakamura et al, 2000,DLBCL,過去：,CHOP,是,10,年前標(biāo)準(zhǔn)的治療,100%,80%,60%,40%,20%,0,0,2,4,6 years,OVERALL SURVIVAL,Regimenpts deaths 3-yr OS,Pro-MACE-CytaBOM 2258854%,MACOP-

2、B2239352%,m-BACOD2339750%,CHOP,2189350%,P = 0.90,Fisher et al, NEJM, 1993,改善,CHOP,的策略,加更多的藥物,劑量增強(qiáng),清髓性的鞏固,CHOP +,長(zhǎng)春地辛,博來霉素,異環(huán)磷酰胺,足葉乙甙,AraC,更多的藥物是否可改善生存,?,是的，,ACVBP,優(yōu)于,CHOP,CHOP,+,足葉乙甙,Pfreundschuh et al, Blood, 2004,更多的藥物是否可改善生存？,: NO,更大劑量的化療是否可改善生存,:,YES (,如果你縮短化療間期,),CHOP 14,優(yōu)于,CHOP 21,CHOP-14,vs.,

3、CHOP-21,p 60,行為狀態(tài),2,LDH 1 x,正常,III,或,IV,期, 1,個(gè)結(jié)外病灶,Shipp et al. N Engl J Med. 1993,IPI,在利妥昔單抗時(shí)代是否仍舊有效,?,OS,IPI,R-IPI,(R = revised),Sehn et al. : NO!,= 0-1,= 2,= 4-5,= 3,= 0,= 1-2,= 3-5,(n= 365),Sehn et al., Blood 2007,IPI,在利妥昔單抗時(shí)代是否仍舊有效,?,OS,IPI,Ziepert et al. : YES!,Ziepert et al., JCO 2010,(n= 106

4、2),在,Sehn,和,Ziepert,的研究中，,高危患者的,OS,可達(dá),50%,，而不是 原先,IPI,的,30%,IPI,是否是唯一的預(yù)后因素,?,Rosenwald, NEJM, 2002,生物學(xué)預(yù)后因素,個(gè)體的生物標(biāo)志,細(xì)胞周期調(diào)節(jié)物,(TP53, p27, cyclinD, ki-67.),凋亡蛋白,(bcl-2, caspases, survivin ),B,細(xì)胞分化,(bcl-6, FOXP1, VEGF ),其他,(IL-10, HLA-DR .),GEP,標(biāo)志,免疫組化,245 DLBCL,R-CHOP,bcl-2 rearr.,bcl-6 rearr.,MYC rearr

5、.,只有,myc,易位是獨(dú)立的預(yù)后因素,Barrans et al., JCO 2010,利妥昔單抗的生物學(xué)預(yù)后因素,例如,:,利妥昔單抗對(duì),GCB,和非,GCB,都有效,GCB,non-GCB,預(yù)后因素不能決定治療選擇,Sehn, L. H. et al. J Clin Oncol; 2005,不同治療時(shí)代的總生存,All Patients in British Columbia: N=294,Roschewski M et al.,Nat Rev Clin Oncol. 2014 Jan;11(1):12-23,.,ABC, activated Bcell,GCB, germinal ce

6、ntre Bcell,PMBL, primary mediastinal Bcell lymphoma,DLBCL,老年,患者的分層標(biāo)準(zhǔn),老年（,60,歲）,預(yù)后不良,60%,預(yù)后不良,超高齡（,8,0,歲）,Meguro A et al. Leuk 53(1):43-9.,【 patient70 years old】: R+70% CHOP,【 patient70 years old】: full dose of R-CHOP,P=0.7,Meguro A et al. Leuk 53(1):43-9.,Three-year PFS with R-70%CHOP for patients 7

7、0years old was not significantly worse than that with full-dose R-CHOP for younger patients,。,R-70% CHOP might be a reasonable choice for patients with DLBCL aged 70 years and older, especially for those with comorbidities,Meguro A et al. Leuk 53(1):43-9.,Aoki K et al. Leuk 54(11):2441-7.,Patients(

8、70 79 years):70% CHOP,patients (80 years) : 50% CHOP,Patients with limited disease: R-CHOP*3+RT or R-CHOP*6-8,Patients with advanced disease :R-CHOP*6-8,DLBCL,將來,1. Roland,T.SkeelHandbook of Cancer,ChemotherapyVersion6,2. Emil,Frei, Cancer Research, 45, 6523-6537, December,1985,中度惡性,NHL,的臨床治療進(jìn)展,1,：,

9、20,世紀(jì),60,年代，罕見治愈,1,；,20,世紀(jì),70,年代研究證實(shí)：中度惡性,NHL,治愈率取決于完全緩解率，新的化療方案提高了治愈率,1,，,緩解,2,年后的病人出現(xiàn)腫瘤復(fù)發(fā)較少見,1,。,20,世紀(jì),80,年代，一篇關(guān)于腫瘤化療的綜述提到，腫瘤治愈性治療的統(tǒng)計(jì)學(xué)定義是：患者生存期超過疾病治療失敗之風(fēng)險(xiǎn)降為零的時(shí)間，例如，無病生存期,1,；,對(duì)大部分腫瘤而言，,治愈率可定義為無病生存期,2,；,DLBCL,治愈概念的發(fā)展史,短期療效,長(zhǎng)期效果,CR,總生存,D,FS,治愈是,DLBCL,治療的最終目標(biāo),權(quán)威專家認(rèn)為,DLBCL,患者的治療目標(biāo)是治愈。,“,Intensive thera

10、py with curative intent should be given to all DLBCL patients who can tolerate such therapy”,(Paul Fields and David Linch),1,“,DLBCL is a chemotherapy-curable lymphoma”,(,James Armitage and Dennis Weisenburger,),2,“Results of the 10-year follow-up of the GELA study underscore the need to treat elder

11、ly patients as young patients, with the use of curative chemotherapy”,(Bertrand Coiffier),3,“,DLBCL is still curable”,(Michael Pfreundschuh),5,“More than 50% of elderly DLBCL patients can be expected to be cured by modern immunochemotherapy R-CHOP” (Michael Pfreundschuh),4,治愈是,DLBCL,患者治療目標(biāo),1.,Fields

12、 PA & Linch DC. Br J Haematol,2012; 157:159,170;,2. Armitage JO 3.,Coiffier B, et al. Blood 2010; 116:2040,2045; 4. Pfreundschuh M. Blood 2010; 116:51035110; 5. Pfreundschuh M 2121.,治療淋巴瘤的主要靶向藥物,單克隆抗體治療,抗,CD20,單抗 抗,CD22,單抗,抗,CD52,單抗,抗,CD30,單抗,放射免疫治療,I,131,抗,CD20,抗體 釔,90,抗,CD20,抗體,其他新型靶向藥物,組蛋白乙?；敢种苿?/p>

13、,蛋白酶體抑制劑,m-TOR,抑制劑,地尼白介素,IL-2R,維甲酸類,抗血管生成治療,彌漫大,B,細(xì)胞淋巴瘤,分子靶向治療進(jìn)展,蛋白酶體抑制劑,蛋白酶體在細(xì)胞周期調(diào)控中起重要作用，因而成為抗腫瘤治療的靶點(diǎn)之一,Bortezomib (Velcade),是已上市的第一個(gè)蛋白酶體抑制劑,臨床前研究顯示,Velcade,抑制多種,B,細(xì)胞性惡性腫瘤（如多發(fā)性骨髓瘤、彌漫大,B,細(xì)胞性,NHL,、套細(xì)胞性,NHL,、,HD,等）的蛋白酶體活性，促進(jìn)細(xì)胞凋亡，增加腫瘤細(xì)胞對(duì)化療和放療的敏感性,ASH 2012,NF-kB Activation,PCI-32765,Staudt LM, et al .

14、BLOOD 2011,ABC,亞型的了解,新治療靶點(diǎn),研究者評(píng)價(jià)的,VBR,最佳療效,最佳療效,末次既往治療,(N=63),VBR (N=59),ORR, n (%),37 (59),51 (,86,),CR,20 (32),31 (,53,),PR,17 (27),20 (,34,),SD, n (%),18 (29),5 (8),PD, n (%),7 (11),3 (5),與末次既往治療相比較，,VBR,提高了緩解率以及緩解,程,度,中位隨診時(shí)間為,177,天；,11,例,(17%),患者仍在治療中,Fowler et al. ASH 2009;Abs 933 data from oral presentation,VEGF,抗體貝伐單抗,Bevacizumab,聯(lián)合,R-CHOP,方案治療初治,DLBCL,的,期臨床研究：,N=13,，,CR 38,，,ORR 85,，,1,年,PFS 77,血清,VEGF,升高主要見于年輕及伴大包塊患者,Bevacizumab,和,Rituximab,的血藥濃度不受聯(lián)合治療的影響，聯(lián)合治療的毒性反應(yīng)可耐受,前瞻性,期,RCT MAIN,研究結(jié)果令人期待,Leuk Lymphoma,2006, 47:998-1005,Thanks,！,