結(jié)外nkt細(xì)胞淋巴瘤楊瑜

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,,,,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(jiàn)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(guò)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)狀組織增生癥致死性中線肉芽腫血管中心性免疫增殖性疾病,

2、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，

3、少有淋巴結(jié)受累由于潰瘍、壞死并發(fā)感染，常有惡臭,,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,Intragumtornchai T, et al. Blood 2009;113:3931-3937.,血中EBV-DNA與疾病過(guò)程？,Whole blood Epstein-Barr virus DNA load as a diagnostic andprognostic sur

4、rogate: extranodal natural 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): 757–763,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 200

5、9; 50(5): 757–763,(A) EBV loads were signi?cantly associated with the stage.,(B) Using the newly proposed model, patients in risk groups 1–3 (0–2 risk factors) had a lower EBV DNA load than those in risk group 4 (3–4 r

6、iskfactors).,(C) Patients who attained an objective response also had a signi?cantly lower EBV PCR load.,(D) Patients with extra-upper aerodigestive tract NK/T-cell lymphoma had signi?cantly higher EBV DNA

7、load than patients with upper aerodigestive tract NK/T-cell lymphoma.,Leukemia & Lymphoma, May 2009; 50(5): 757–763,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),Extranoda

8、l Natural Killer T-Cell Lymphoma, Nasal-Type: APrognostic Model From a Retrospective Multicenter 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（Ⅲ/Ⅳ）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, o

9、ne 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

10、2：64.2% group 3：34.4%group 4：6.6%,5年OS,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(guó)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 versusradiochemoth

11、erapy 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

12、)1–6 cycles of anthracycline-based chemotherapeutic regimens.,Med Oncol (2010) 27:798–806,59.2%,52.3%,Fig. 2 The survival status of allpatients according to treatmentmodality. (a) OS. (b) PFS. RTradiotherapy alone, R

13、CTradiochemotherapy,57.9%,61.5%,P=0.47,結(jié)論：化療聯(lián)合放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 JCOG0

14、211,入組：33例新診斷局限期鼻的NK/T細(xì)胞淋巴瘤放療劑量：ⅠE期 50GY；ⅡE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. © 2009,4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 t

15、reated with radiotherapy and two thirds dose of dexamethasone, etoposide, ifosfamide, and carboplatin.,78%,67%,歷史對(duì)照：?jiǎn)斡梅暖烵S 45%,Fig 2. Effect of complete response (CR) on (A) overall survival and (B) progression-free su

16、rvival 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Ⅰ、Ⅱ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

17、基礎(chǔ),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

18、 Clin Oncol 27:6027-6032. © 2009,30例新診斷ⅠE、ⅡE結(jié)外NK/T細(xì)胞淋巴瘤入組,Fig 2. Summary of treatment outcomes and treatment failures. CCRT, concurrentchemoradiotherapy; CR, complete response; VIPD, etoposide, ifosfamide, cisplati

19、n, 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

20、nasal ENKTL.,Ef?cacy 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(guó)13個(gè)中心含L-門冬酰胺酶

21、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歲2.0/m2)Dexamethasone 40mg d1-4

22、 （>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： ① 3周期后對(duì)先前未放療的局限性病灶予以防療 ② 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

23、 ③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(guò)敏,結(jié)論,L-門冬酰胺酶為基礎(chǔ)的治療應(yīng)該成為結(jié)外NK/T細(xì)胞淋巴瘤的解救方案，尤其是播散性的疾病是否成為一線治療，還需要前瞻性研究驗(yàn)證,指南推薦,Risk factors,小結(jié),ENKTL是少見(jiàn)并且特殊的一個(gè)類型，發(fā)