结外NKT细胞淋巴瘤(杨瑜)

1、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 杨瑜未成熟未成熟NK细胞细胞 l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细胞肿瘤细胞肿瘤WHO-2008成熟成熟NK细胞细胞 ：l慢性NK细胞淋巴增殖性疾患l侵袭性NK细胞白血病l结外NK/T细胞淋巴瘤，鼻型结外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

2、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

3、、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 136例结外NK/T细胞淋巴瘤回顾性分析鼻的鼻的鼻外鼻外进展期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.血中EBV-DNA与疾病过程？Whole blood Epstein-Barr virus DNA load as a diagnostic andprognostic surrogate: extranodal natural

4、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 significantly associated with the stage.(B) Using the newly proposed model, pa

5、tients 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 significantly lower EBV PCR load.(D) Patients with extra-upper aerodigestive tract NK/T-cell lymphoma had significantly higher EB

6、V 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 Multic

7、enter 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 Oncology1 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

8、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-celllymphomaEarly stage (stage IE: 51, stage IIE: 13) nasal NK/T-cell lymphoma (NNTCL)23 received radiotherapy (RT) alone, 41

9、cases were treated with radiochemotherapy (RCT)16 cycles of anthracycline-based chemotherapeutic regimens. Med Oncol (2010) 27:79880659.2%52.3%Fig. 2 The survival status of allpatients according to treatmentmodality. (a) OS. (b) PFS. RTradiotherapy alone, RCTradiochemotherapy57.9%61.5%P=0.47结论：化疗联合放

10、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 Level 1Level 2DXM40mg40mgD1-

11、3VP1667mg/m2100mg/m2D1-3IFO1.0/m21.5/m2D1-3CBP200mg/m2300mg/m2D14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

12、 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 Concurre

13、nt Radiation andWeeklyCisplatin Followed by VIPD Chemotherapy in NewlyDiagnosed, Stage IE to IIE, Nasal, Extranodal NK/T-CellLymphoma: Consortium for Improving Survival ofLymphoma StudyJ 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.

14、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

15、 to IIE nasal ENKTL.Efficacy 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、

16、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