1、結(jié)外NK/T細(xì)胞淋巴瘤,鼻型(Extranodal NK/T-cell lymphoma,nasal type)福建省腫瘤醫(yī)院 楊瑜未成熟未成熟NK細(xì)胞細(xì)胞 l母細(xì)胞性漿細(xì)胞樣樹狀突細(xì)胞腫瘤（以前稱為母細(xì)胞性NK細(xì)胞白血病/淋巴瘤）NK細(xì)胞腫瘤細(xì)胞腫瘤WHO-2008成熟成熟NK細(xì)胞細(xì)胞 ：l慢性NK細(xì)胞淋巴增殖性疾患l侵襲性NK細(xì)胞白血病l結(jié)外NK/T細(xì)胞淋巴瘤，鼻型結(jié)外NK/T細(xì)胞淋巴瘤，鼻型發(fā)病具有獨(dú)特的地域分布：亞洲、中南美洲常見于成人，中位年齡50歲，男性多發(fā)與EBV感染密切相關(guān)（可能的發(fā)病機(jī)制）臨床過程呈侵襲性曾用名稱血管中心性T細(xì)胞淋巴瘤惡性中線網(wǎng)狀組織增生癥多形性網(wǎng)狀組織增生癥

2、致死性中線肉芽腫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。多數(shù)也表達(dá)細(xì)胞毒性顆粒相關(guān)蛋白（如粒酶B、TIA-1和穿孔素） 當(dāng)CD56(-)、EBV(+)、細(xì)胞毒性分子（+）診斷NK/T 而CD56(+)、EBV(-)、細(xì)胞毒性分子（-）診斷外周T臨床表現(xiàn) 臨床表現(xiàn)較為獨(dú)特，少有淋巴結(jié)受累 由于潰瘍、壞死并發(fā)感染，常有惡臭鼻的，常局限于：上呼吸消化道包括鼻腔、鼻咽、鼻旁竇、喉咽和喉鼻外部位：如皮膚

3、、睪丸、胃腸道、軟組織和脾臟等，即為鼻型結(jié)外NK/T細(xì)胞淋巴瘤，鼻型組織學(xué)相同，治療及預(yù)后不一樣 136例結(jié)外NK/T細(xì)胞淋巴瘤回顧性分析鼻的鼻的鼻外鼻外進(jìn)展期27%68%B癥狀39%54%中位OS(局限期)2.96年0.36年中位OS(進(jìn)展期)0.8年0.28年 Intragumtornchai T, et al. Blood 2009;113:3931-3937.血中EBV-DNA與疾病過程？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 檢測(cè)全血EBV載量 探討其與EBV相關(guān)性淋巴瘤的診斷、預(yù)后等的關(guān)系Leukemia & Lymphoma, May 2009; 50(5): 757763全血EBV-DNA病毒載量與臨床分期、治療的反應(yīng)及疾病狀態(tài)的相關(guān)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認(rèn)為：外周血EBV-DNA載量對(duì)于結(jié)外NK/T細(xì)胞淋巴瘤也是需要檢測(cè)的一個(gè)指標(biāo)，與疾病分期、治療反應(yīng)、疾病狀態(tài)都有相關(guān)性，可進(jìn)一步開展前瞻性研究。預(yù)后指數(shù)Extranodal Natural Killer T-Cell Lymphoma, Nasal-Type: APrognostic Model From a Retrospective Multic

7、enter Study回顧性分析10中心262例結(jié)外NK/T細(xì)胞淋巴瘤不利因素：B癥狀LDH升高分期（/）區(qū)域淋巴結(jié)受累（N1-N3，非M1）分四個(gè)危險(xiǎn)組：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不能區(qū)分：低危與低中危 中高危與高危76%0%結(jié)論：新的預(yù)后模型比國際預(yù)后指數(shù) 能更好區(qū)分和預(yù)測(cè)結(jié)外NK/T細(xì) 胞淋巴瘤預(yù)后。K-PI治療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結(jié)論：化療聯(lián)合放

10、療不能改善早期鼻的NK/T 細(xì)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 入組：33例新診斷局限期鼻的NK/T細(xì)胞淋巴瘤 放療劑量：E期 50GY；E期 50.4GY 化療方案：DeVIC 3療程 登記入組后7天內(nèi)同時(shí)開始J Clin Oncol 27:5594-5600. 2009 Level 1Level 2DXM40mg40mgD1-

11、3VP1667mg/m2100mg/m2D1-3IFO1.0/m21.5/m2D1-3CBP200mg/m2300mg/m2D14藥聯(lián)用，三周重復(fù)，連用3療程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%歷史對(duì)照：單用放療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.結(jié)論：該研究結(jié)果表明，聯(lián)合DeVIC方案的同步 化放療，對(duì)于初治的、鼻的NK/T細(xì)胞 淋巴瘤是安全和有效的，值得推廣，同時(shí) 也為此病的進(jìn)一步研究提供了基礎(chǔ)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例新診斷E、E結(jié)外NK/T細(xì)胞淋巴瘤入組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例難治或復(fù)發(fā)結(jié)外NK/T細(xì)胞淋巴瘤，法國13個(gè)中心 含L-門冬酰胺酶方案BLOOD, 10 FEBRUARY 2011 VOLUME 117, NUMBER 6 L-asparaginase 6000u/m2 d2、

16、4、6、8 im methotrexate 3.0/m2 d1 （70歲2.0/m2)Dexamethasone 40mg d1-4 （70歲20mg) 21天，3療程 治療前后監(jiān)測(cè)血清抗凝血酶及纖維蛋白原水平 水化、堿化及四氫葉酸解救 預(yù)防性使用抗菌及抗病毒藥 后續(xù)治療： 3周期后對(duì)先前未放療的局限性病灶予以防療 對(duì)一般狀況好的播散性病變予自體外周血干細(xì)胞 支持下的大劑量化療 其余前期化療有效的繼續(xù)原方案至6療程結(jié)果 3周期化療后18個(gè)病人可評(píng)價(jià)療效，14個(gè)獲得療效，11個(gè)達(dá)CR(61%) 中位總生存時(shí)間是1年，中位緩解期12月 最主要毒性：肝功損害、骨髓抑制、過敏結(jié)論 L-門冬酰胺酶為基礎(chǔ)的治療應(yīng)該