结外NKT细胞淋巴瘤课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,结外,NK/T,细胞淋巴瘤,鼻型,(Extranodal NK/T-cell lymphoma,nasal type),结外NK/T细胞淋巴瘤,鼻型(Extranodal NK/T,1,未成熟,NK,细胞,母细胞性浆细胞样树状突细胞肿瘤,（以前称为母细胞性,NK,细胞,白血病,/,淋巴瘤）,NK,细胞肿瘤,WHO-2008,成熟,NK,细胞,：,慢性,NK,细胞淋巴增殖性疾患,侵袭性,NK,细胞白血病,结外,NK/T,细胞淋巴瘤，鼻型,未成熟NK细胞 NK细胞肿瘤成熟NK细胞 ：,2,结外,NK/T,细胞淋巴瘤，鼻型,发病具有独特的地域分布：亚洲、中南美洲,常见于成人，中位年龄,50,岁，男性多发,与,EBV,感染密切相关（可能的发病机制）,临床过程呈侵袭性,结外NK/T细胞淋巴瘤，鼻型发病具有独特的地域分布：亚洲,3,曾用名称,血管中心性,T,细胞淋巴瘤,恶性中线网状组织增生症,多形性网状组织增生症,致死性中线肉芽肿,血管中心性免疫增殖性疾病,曾用名称血管中心性T细胞淋巴瘤,4,典型的免疫表型,CD20-, CD2+, CD56+, CD7+, CD8+, CD43+, CD45RO+, cytoplasmic CD3+(surface CD3-),，,EBV+,，通常缺乏,TCR,和免疫球蛋白基因重排。,多数也表达细胞毒性颗粒相关蛋白（如粒酶,B,、,TIA-1,和穿孔素）,当,CD56(-),、,EBV(+),、细胞毒性分子（,+,）诊断,NK/T,而,CD56(+),、,EBV(-),、细胞毒性分子（,-,）诊断外周,T,典型的免疫表型CD20-, CD2+, CD56+, CD7,5,临床表现,临床表现较为独特，少有淋巴结受累,由于溃疡、坏死并发感染，常有恶臭,临床表现临床表现较为独特，少有淋巴结受累,6,结外NKT细胞淋巴瘤课件,7,结外NKT细胞淋巴瘤课件,8,结外NKT细胞淋巴瘤课件,9,结外NKT细胞淋巴瘤课件,10,结外NKT细胞淋巴瘤课件,11,结外NKT细胞淋巴瘤课件,12,鼻的，常局限于：上呼吸消化道包括鼻腔、鼻咽、鼻旁窦、喉咽和喉,鼻外部位：如皮肤、睾丸、胃肠道、软组织和脾脏等，即为鼻型,结外,NK/T,细胞淋巴瘤，鼻型,组织学相同，治疗及预后不一样,鼻的，常局限于：上呼吸消化道包括鼻腔、鼻咽、鼻旁窦、喉咽和喉,13,136,例结外,NK/T,细胞淋巴瘤回顾性分析,鼻的,鼻外,进展期,27%,68%,B,症状,39%,54%,中位,OS(,局限期,),2.96,年,0.36,年,中位,OS(,进展期,),0.8,年,0.28,年,Intragumtornchai T, et al. Blood 2009;113:3931-3937.,136例结外NK/T细胞淋巴瘤回顾性分析鼻的鼻外进展期27,14,血中,EBV-DNA,与疾病过程？,血中EBV-DNA与疾病过程？,15,Whole blood Epstein-Barr virus DNA load as a diagnostic andprognostic surrogate: extranodal natural killer/T-cell lymphoma,101,例淋巴瘤及,105,非淋巴瘤患者,检测全血,EBV,载量,探讨其与,EBV,相关性淋巴瘤的诊断、预后等的关系,Leukemia 50(5): 757763,Whole blood Epstein-Barr virus,16,全血,EBV-DNA,病毒载量,与临床分期、治疗的反应及,疾病状态的相关性,Leukemia 50(5): 757763,(A) EBV loads were signicantly associated with the stage.,(B) Using the newly proposed model, patients,in risk groups 13 (02 risk factors) had a lower,EBV DNA load than those in risk group 4 (34 risk,factors).,全血EBV-DNA病毒载量Leukemia & Lympho,17,(C) Patients who attained an objective response also,had a signicantly lower EBV PCR load.,(D) Patients with extra-upper aerodigestive tract NK/T-cell,lymphoma had signicantly higher EBV DNA load than,patients with upper aerodigestive tract NK/T-cell,lymphoma.,Leukemia 50(5): 757763,(C) Patients who attained an o,18,结外NKT细胞淋巴瘤课件,19,认为：,外周血,EBV-DNA,载量对于结外,NK/T,细胞淋巴瘤,也是需要检测的一个指标，与疾病分期、治疗反应、,疾病状态都有相关性，可进一步开展前瞻性研究。,认为：外周血EBV-DNA载量对于结外NK/T细胞淋巴瘤,20,预后指数,预后指数,21,Extranodal Natural Killer T-Cell Lymphoma, Nasal-Type: APrognostic Model From a Retrospective Multicenter Study,回顾性分析,10,中心,262,例结外,NK/T,细胞淋巴瘤,不利因素：,B,症状,LDH,升高,分期（,/,）,区域淋巴结受累（,N1-N3,，非,M1,）,分四个危险组：,group 1, no,group 2, one factor;,group 3, two factors;,group 4, three or four,J Clin Oncol 24:612-618. 2006 by American Society of Clinical Oncology,1,低危,2,低中危,3,中高危,4,高危,Extranodal Natural Killer T-Ce,22,结外NKT细胞淋巴瘤课件,23,结外NKT细胞淋巴瘤课件,24,group 1,：,80.9%,group 2,：,64.2%,group 3,：,34.4%,group 4,：,6.6%,5,年,OS,group 1：80.9%5年OS,25,IPI,不能区分,：低危与低中危,中高危与高危,IPI不能区分：低危与低中危,26,76%,0%,76%0%,27,结论：新的预后模型比国际预后指数,能更好区分和预测结外,NK/T,细,胞淋巴瘤预后。,K-PI,结论：新的预后模型比国际预后指数K-PI,28,治疗,治疗,29,Treatment outcome of radiotherapy alone versusradiochemotherapy in early stage nasal natural killer/T-celllymphoma,Early stage (,stage IE: 51, stage IIE: 13,) nasal NK/T-cell lymphoma (NNTCL),23 received radiotherapy (RT) alone, 41 cases were treated with radiochemotherapy (RCT),16 cycles of anthracycline-based chemotherapeutic regimens.,Med Oncol (2010) 27:798806,Treatment outcome of radiother,30,59.2%,52.3%,59.2%52.3%,31,Fig. 2 The survival status of all,patients according to treatment,modality. (a) OS. (b) PFS. RT,radiotherapy alone, RCT,radiochemotherapy,57.9%,61.5%,P=0.47,Fig. 2 The survival status of,32,结论：化疗联合放疗不能改善早期鼻的,NK/T,细胞淋巴瘤的生存,结论：化疗联合放疗不能改善早期鼻的NK/T,33,Phase I/II Study of Concurrent Chemoradiotherapy forLocalized Nasal Natural Killer/T-Cell Lymphoma: JapanClinical Oncology Group Study JCOG0211,入组：,33,例新诊断局限期鼻的,NK/T,细胞淋巴瘤,放疗剂量：,E,期,50GY,；,E,期,50.4GY,化疗方案：,DeVIC 3,疗程,登记入组后,7,天内同时开始,J Clin Oncol 27:5594-5600. 2009,Phase I/II Study of Concurrent,34,Level 1,Level 2,DXM,40mg,40mg,D1-3,VP16,67mg/m2,100mg/m2,D1-3,IFO,1.0/m2,1.5/m2,D1-3,CBP,200mg/m2,300mg/m2,D1,4,药联用，三周重复，连用,3,疗程,DeVIC,方案,Level 1Level 2DXM40mg40mgD,35,结外NKT细胞淋巴瘤课件,36,Fig 1. (A) Overall survival and (B) progression-free survival,of patients treated with radiotherapy and two thirds dose of,dexamethasone, etoposide, ifosfamide, and carboplatin.,78%,67%,历史对照：单用放疗,OS 45%,Fig 1. (A) Overall survival an,37,Fig 2. Effect of complete response (CR) on (A) overall,survival and (B) progression-free survival of patients treated,with radiotherapy and two thirds dose of dexamethasone,etoposide, ifosfamide, and carboplatin.,Fig 2. Effect of complete resp,38,结论：该研究结果表明，联合,DeVIC,方案的同步,化放疗，对于初治的,、,鼻的,NK/T,细胞,淋巴瘤是安全和有效的，值得推广，同时,也为此病的进一步研究提供了基础,结论：该研究结果表明，联合DeVIC方案的同步,39,Phase II Trial of Concurrent Radiation andWeeklyCisplatin Followed by VIPD Chemotherapy in NewlyDiagnosed, Stage IE to IIE, Nasal, Extranodal NK/T-CellLymphoma: Consortium for Improving Survival ofLymphoma Study,J Clin Oncol 27:6027-6032. 2009,30,例新诊断,E,、,E,结外,NK/T,细胞淋巴瘤入组,Phase II Trial of Concurrent R,40,Fig 2. Summary of treatment outcomes and treatment failures. CCRT, concurrent,chemoradiotherapy; CR, complete response; VIPD, etoposide, ifosfamide, cisplatin, and dexamethasone; PD, progressive disease; PR, partial response.,Fig 2. Summary of treatment ou,41,结外NKT细胞淋巴瘤课件,42,3,年：,PFS 85.19%,、,OS 86.28%,3年：PFS 85.19%、 OS 86.28%,43,结外NKT细胞淋巴瘤课件,44,In conclusion, CCRT followed by VIPD chemotherapy,can be a,feasible,and,effective,treatment strategy for,stages IE to IIE nasal ENKTL.,In conclusion, CCRT followed b,45,Efcacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDexregimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma,a phase 2 study,19,例难治或复发结外,NK/T,细胞淋巴瘤，法国,13,个中心,含,L-,门冬酰胺酶方案,BLOOD, 10 FEBRUARY 2011 VOLUME 117, NUMBER 6,L-asparaginase 6000u/m,2,d2,、,4,、,6,、,8 im,methotrexate 3.0/m,2,d1,（,70,岁,2.0/m,2,),Dexamethasone 40mg d1-4,（,70,岁,20mg),21,天，,3,疗程,Efcacy of L-asparaginase with,46,治疗前后监测血清抗凝血酶及纤维蛋白原水平,水化、碱化及四氢叶酸解救,预防性使用抗菌及抗病毒药,后续治疗,： ,3,周期后对先前未放疗的局限性病灶予以防疗, 对一般状况好的播散性病变予自体外周血干细胞,支持下的大剂量化疗,其余前期化疗有效的继续原方案至,6,疗程,治疗前后监测血清抗凝血酶及纤维蛋白原水平,47,结外NKT细胞淋巴瘤课件,48,结外NKT细胞淋巴瘤课件,49,结果,3,周期化疗后,18,个病人可评价疗效，,14,个获得疗效，,11,个达,CR(61%),中位总生存时间是,1,年，中位缓解期,12,月,最主要毒性：肝功损害、骨髓抑制、过敏,结果3周期化疗后18个病人可评价疗效，14个获得疗效，11个,50,结论,L-,门冬酰胺酶为基础的治疗应该成为结外,NK/T,细胞淋巴瘤的解救方案，尤其是播散性的疾病,是否成为一线治疗，还需要前瞻性研究验证,结论L-门冬酰胺酶为基础的治疗应该成为结外NK/T细胞淋巴瘤,51,指南推荐,指南推荐,52,Risk factors,Risk factors,53,结外NKT细胞淋巴瘤课件,54,小结,ENKTL,是少见并且特殊的一个类型,，发病呈地域性分布，东亚及中南美洲高发，男性多于女性，中位年龄,50,岁,EBV,与本病密切相关,侵袭性病程，原发于鼻及鼻周围的上呼吸消化道部位比鼻外部位的预后要好,对放射敏感，原发于鼻的局限期病例有可能被治愈,同期放化疗对于局限期存在危险因素的，有望提高疗效和改善预后,L-,门冬酰胺酶为基础的化疗对进展期患者有效，值得进一步应用和研究,小结ENKTL是少见并且特殊的一个类型，发病呈地域性分布，东,55,谢谢！,谢谢！,56,