结外NKT细胞淋巴瘤杨瑜

结外NK/T细胞淋巴瘤,鼻型(Extranodal NK/T-cell lymphoma,nasal type),福建省肿瘤医院 杨瑜,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,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,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,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,结外NK/T细胞淋巴瘤，鼻型,组织学相同，治疗及预后不一样,136例结外NK/T细胞淋巴瘤回顾性分析,Intragumtornchai T, et al. Blood 2009;113:3931-3937.,血中EBV-DNA与疾病过程？,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 & Lymphoma, May 2009; 50(5): 757763,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 & Lymphoma, May 2009; 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 riskfactors).,(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 & Lymphoma, May 2009; 50(5): 757763,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。,预后指数,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,group 1：80.9%group 2：64.2% group 3：34.4%group 4：6.6%,5年OS,IPI不能区分：低危与低中危 中高危与高危,76%,0%,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,治疗,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) 27:798806,59.2%,52.3%,Fig. 2 The survival status of allpatients according to treatmentmodality. (a) OS. (b) PFS. RTradiotherapy alone, RCTradiochemotherapy,57.9%,61.5%,P=0.47,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,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. 2009,4药联用，三周重复，连用3疗程,DeVIC方案,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 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.,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,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,Fig 2. Summary of treatment outcomes and treatment failures. CCRT, concurrentchemoradiotherapy; CR, complete response; VIPD, etoposide, ifosfamide, cisplatin, and dexamethasone; PD, progressive disease; PR, partial response.,3年：PFS 85.19%、 OS 86.28%,In conclusion, CCRT followed by VIPD chemotherapy can be a feasible and effective treatment strategy forstages IE to IIE nasal ENKTL.,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/m2 d2、4、6、8 im methotrexate 3.0/m2 d1 （70岁2.0/m2)Dexamethasone 40mg d1-4 （70岁20mg),21天，3疗程,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,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