课件：结外细胞淋巴瘤杨瑜.ppt

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 and prognostic 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,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).,(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,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: A Prognostic 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,2019/8/21,29,可编辑,治疗,Treatment outcome of radiotherapy alone versus radiochemotherapy in early stage nasal natural killer/T-cell lymphoma,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 all patients according to treatment modality. (a) OS. (b) PFS. RT radiotherapy alone, RCT radiochemotherapy,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 for Localized Nasal Natural Killer/T-Cell Lymphoma: Japan Clinical 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 andWeekly Cisplatin Followed by VIPD Chemotherapy in Newly Diagnosed, Stage IE to IIE, Nasal, Extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma 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, concurrent chemoradiotherapy; 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 for stages IE to IIE nasal ENKTL.,Efcacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) 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细胞淋巴瘤的解救方案，尤其是播散性的疾病 是否成为一线治