胃肠结外淋巴瘤.ppt

1、,原发胃肠结外淋巴瘤诊疗进展,刘艳艳 河南省肿瘤医院淋巴综合内科,P-MAR-2019.06-046 Valid Until 2019.06,专业资料，仅供医药卫生专业人士使用,声明,本幻灯片代表个人观点。处方请参考国家食品药品监督管理总局批准的药物说明书。,定义,来源于淋巴结外的淋巴组织 甚至来源于正常情况下不含淋巴组织的部位 当结内和结外病变同时存在时，定义较困难,发病率,占非霍奇金淋巴瘤的25%,淋巴瘤,淋巴结,淋巴结外,胃肠道,非胃肠道,胃 : B-cell MALT DLBCL H. Pylori,肠道 : T-cell Celiac disease,睾丸脑T/NK 鼻型,INTER

2、NATIONAL EXTRANODAL LYMPHOMA STUDYGROUP,Extranodal Lymphoma Survival by histology and site in the IELSG series,少见 : 所有胃肠道肿瘤的3% 绝大多数胃肠道淋巴瘤来源于胃,原发胃肠道淋巴瘤,P Koch J Clin Oncol 2019,15%,3%,75%,Non Hodgkins Lymphoma Classification Project. Blood 2019;89:3909-18,Frequency % G Gastric I Intestin Nodal site,1

3、.4%G - 4%I,0%G - 25%I,0%G - 20%I,胃肠道淋巴瘤分类,Mantle cell L.,Diffuse large B cell lymphoma,T-cell lymphoma,Burkitt. L,MALT Lymphoma,1%G - 20% (colon),Follicular L.,38%G - 10%I,60%,系统检查分期,MALT lymphoma : ESMO GUIDELINES Dreyling M, Thieblemont C. et al. Ann Oncol 2019,Auto-antigens,- Thyroid Hashimoto th

4、yroiditis - Salivary gland Myoepithelial sialoadenitis +/ - Sjgren S. - - Lung Lymphoid interstitial pneumopathy,MZL（边缘区淋巴瘤）: 与慢性抗原刺激相关,MALT Lymphomas,Site Infectious agents - Stomach Helicobacter pylori - Intestin Campylobacter jejuni - Ocular adnexa Chlamydia psittaci - skin Borrelia burgdorferi,H

5、epatitis C Virus,Microbial pathogens,1.,2.,+,Splenic MZL,Isaacson P, Wright DH. Cancer 1983,HELICOBACTER PYLORI in STOMACH,MZL: associated with a chronic antigenic stimulation,chronic Ag stimulation - chronic inflammation,MALT CONCEPT,MALT淋巴瘤常见的遗传损伤,NF-KB activation,Bertoni F. et al. Oncology 2019,N

6、ormal stomach,Chronic gastritis MALT Lymphoma,+ additional factors: host, environment, genetic,HP,NFKB,t(11;18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1,E. De Kerviler Saint-Louis Hospital, Paris,胃MALT 淋巴瘤内镜,Pseudogastritis 30%,Nodular infiltration 25%,Ulcers 45%,JC Delchier Henri Mondor Hospital,

7、 Crteil,Normal stomach,Chronic gastric MALT Lymphoma,+ additional factors: host, environment, genetic,HP,NFKB,t(11;18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1,ATB,Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wndisch, JCO 2019,依赖H. Pylori的胃MALT 淋巴瘤的治疗,Hp. eradication,Complete response: 60% - 10

8、0% Response: 3 to 28 months ! Resistance associated to t(11;18),Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wndisch, JCO 2019,Lymphoma,Reference n stagingCR ratetime to CR relapses procedure (%) (mos.) (n) Savio, 201912 CT 84 2-40 Pinotti, 201945CT 67 3-182 Neubauer, 2019 50CTEUS 80 1-95 Nobre L

9、eitao, 201917 CT+EUS 100 1-121 Steinbach, 201923CTEUS 56 3-450 Montalban, 201919CTEUS 95 2-19 0Ruskone-Formestraux, 201924CT+EUS 79 2-18 2 LY03 interim analysis, 2000 190CT 62 3-2415,抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤,After 5 years = 71%,Median follow-up = 7 years,Fischbach et al, Gut 56:1685-7, 2019 Pinot

10、ti et al, 10-ICML Abstract # 361 Stathis A et al, Ann Oncol 2009,n = 120 patients,抗生素治疗后的缓解期,Normal stomach,Chronic gastric MALT Lymphoma,HP,t(11;18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1,DLBCL,p53 deletion, p16 deletion,Gastric DLBCL Dependant to Hp. ?,10 pts with Gastric DLBCL - Stage IE or I

11、IE PPI-amoxicillin-clarithromycin for 7 days,JC Delchier et al. IELSG 2019,Biomarkers associated with antigen dependance,RT in localized gastric MALT lymphoma,Author n RT dose (Gy) FFP Schechter, 20191728-43100% at 2 yr Tsang, 2019 920-30100% at 5 yr Yahalom, 20195130 median89% at 4 yr Hitchcock, 20

12、19 934 median78% (100% local) Goda JS, 2019 25 25-30 79% at 5 yr,烷化剂单药治疗,24 例患者, 17 例stage I ，7 例stage IV Cyclophosphamide or Chlorambucil for 8-24 mos. 100% ORR (75% CR) 5-year EFS: 50% 5-year OS: 75% 5 relapses at initial sites (1 with transformation),Hammel et al, JCO 2019,(cyclophosphamide or ch

13、lorambucil),Lymphoma,Nodal,Extranodal,Gastro-intestinal,Non Gastro-intestinal,Gastric : B-cell MALT DLBCL H. Pylori,Intestinal : T-cell Celiac disease,TestisBrainT/NK nasal Type,胃肠道弥漫大B细胞淋巴瘤,60% of primary GI lymphoma,GI DLBCL,临床表现,侵袭性 B 症状 大肿块 坏死 穿孔风险: 10%!,P Koch J Clin Oncol 2019:19:3861,GI DLBCL

14、,治疗目的,One Goal,To cure the patient with the first line of treatment,GI DLBCL,TREATMENT,No surgery Biomarkers are needed to detect the Hp. - dependant gastric DLBCL Standard R-CHOP,GI DLBCL,Lymphoma,Nodal,Extranodal,Gastro-intestinal,Non Gastro-intestinal,Gastric : B-cellMALTDLBCLH. Pylori,Intestinal : T-cell Celiac disease,TestisBrainT/NK nasal Type,EATL,肠病型小肠T细胞淋巴瘤(EATL),通常有谷蛋白敏感性肠病既往史 腹腔疾病患者: Relative risk of EATL x 50-100 临床表现: 多发空肠溃疡 Extension: GI tract : estomac, colon Extra-intestinal : blood, skin, lung,EATL,EATL,粘膜内T淋巴细胞增殖 Phenotype T CD3+CD