未成熟NK細(xì)胞

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WHO-2008成熟NK細(xì)胞

：慢性NK細(xì)胞淋巴增殖性疾患侵襲性NK細(xì)胞白血病結(jié)外NK/T細(xì)胞淋巴瘤，鼻型當(dāng)前第1頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)

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(guò)程呈侵襲性當(dāng)前第2頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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當(dāng)前第3頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)典型的免疫表型CD20-,CD2+,CD56+,CD7+,CD8+,CD43+,CD45RO+,cytoplasmicCD3+(surfaceCD3-)，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當(dāng)前第4頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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，常有惡臭當(dāng)前第5頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第6頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第7頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第8頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第9頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第10頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第11頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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、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)后不一樣當(dāng)前第12頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)136例結(jié)外NK/T細(xì)胞淋巴瘤回顧性分析鼻的鼻外進(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IntragumtornchaiT,etal.Blood2009;113:3931-3937.當(dāng)前第13頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)血中EBV-DNA與疾病過(guò)程？當(dāng)前第14頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)WholebloodEpstein-BarrvirusDNAloadasadiagnosticand

prognosticsurrogate:extranodalnaturalkiller/T-celllymphoma101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,May2009;50(5):757–763當(dāng)前第15頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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,May2009;50(5):757–763(A)EBVloadsweresigni?cantlyassociatedwiththestage.(B)Usingthenewlyproposedmodel,patientsinriskgroups1–3(0–2riskfactors)hadalowerEBVDNAloadthanthoseinriskgroup4(3–4riskfactors).當(dāng)前第16頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)(C)Patientswhoattainedanobjectiveresponsealsohadasigni?cantlylowerEBVPCRload.(D)Patientswithextra-upperaerodigestivetractNK/T-celllymphomahadsigni?cantlyhigherEBVDNAloadthanpatientswithupperaerodigestivetractNK/T-celllymphoma.Leukemia&Lymphoma,May2009;50(5):757–763當(dāng)前第17頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第18頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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。當(dāng)前第19頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)預(yù)后指數(shù)當(dāng)前第20頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)ExtranodalNaturalKillerT-CellLymphoma,Nasal-Type:A

PrognosticModelFromaRetrospectiveMulticenterStudy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：group1,nogroup2,onefactor;group3,twofactors;group4,threeorfourJClinOncol24:612-618.?2006byAmericanSocietyofClinicalOncology1

低危2低中危3

中高危4

高危當(dāng)前第21頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第22頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第23頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)group1：80.9%group2：64.2%group3：34.4%group4：6.6%5年OS當(dāng)前第24頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)IPI不能區(qū)分：低危與低中危

中高危與高危當(dāng)前第25頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)76%0%當(dāng)前第26頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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當(dāng)前第27頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)治療當(dāng)前第28頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Treatmentoutcomeofradiotherapyaloneversus

radiochemotherapyinearlystagenasalnaturalkiller/T-cell

lymphomaEarlystage(stageIE:51,stageIIE:13)nasalNK/T-celllymphoma(NNTCL)23receivedradiotherapy(RT)alone,41casesweretreatedwithradiochemotherapy(RCT)1–6cyclesofanthracycline-basedchemotherapeuticregimens.MedOncol(2010)27:798–806當(dāng)前第29頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)59.2%52.3%當(dāng)前第30頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Fig.2Thesurvivalstatusofallpatientsaccordingtotreatmentmodality.(a)OS.(b)PFS.RTradiotherapyalone,RCTradiochemotherapy57.9%61.5%P=0.47當(dāng)前第31頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)結(jié)論：化療聯(lián)合放療不能改善早期鼻的NK/T細(xì)胞淋巴瘤的生存當(dāng)前第32頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)PhaseI/IIStudyofConcurrentChemoradiotherapyfor

LocalizedNasalNaturalKiller/T-CellLymphoma:Japan

ClinicalOncologyGroupStudyJCOG0211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：DeVIC3療程登記入組后7天內(nèi)同時(shí)開始JClinOncol27:5594-5600.?2009當(dāng)前第33頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Level1Level2DXM40mg40mgD1-3VP1667mg/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方案當(dāng)前第34頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第35頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Fig1.(A)Overallsurvivaland(B)progression-freesurvivalofpatientstreatedwithradiotherapyandtwothirdsdoseofdexamethasone,etoposide,ifosfamide,andcarboplatin.78%67%歷史對(duì)照：?jiǎn)斡梅暖烵S45%當(dāng)前第36頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Fig2.Effectofcompleteresponse(CR)on(A)overallsurvivaland(B)progression-freesurvivalofpatientstreatedwithradiotherapyandtwothirdsdoseofdexamethasone,etoposide,ifosfamide,andcarboplatin.當(dāng)前第37頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)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)一步研究提供了基礎(chǔ)當(dāng)前第38頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)PhaseIITrialofConcurrentRadiationandWeekly

CisplatinFollowedbyVIPDChemotherapyinNewly

Diagnosed,StageIEtoIIE,Nasal,ExtranodalNK/T-Cell

Lymphoma:ConsortiumforImprovingSurvivalof

LymphomaStudyJClinOncol27:6027-6032.?200930例新診斷ⅠE、ⅡE結(jié)外NK/T細(xì)胞淋巴瘤入組當(dāng)前第39頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Fig2.Summaryoftreatmentoutcomesandtreatmentfailures.CCRT,concurrentchemoradiotherapy;CR,completeresponse;VIPD,etoposide,ifosfamide,cisplatin,anddexamethasone;PD,progressivedisease;PR,partialresponse.當(dāng)前第40頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第41頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)3年：PFS85.19%、OS86.28%當(dāng)前第42頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)當(dāng)前第43頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Inconclusion,CCRTfollowedbyVIPDchemotherapycanbeafeasibleandeffectivetreatmentstrategyforstagesIEtoIIEnasalENKTL.當(dāng)前第44頁(yè)\共有52頁(yè)\編于星期五\11點(diǎn)Ef?cacyofL-asparaginasewithmethotrexateanddexamethasone(AspaMetDex

regimen)inpatientswithrefractoryorrelapsingextranodalNK/T-celllymphoma,

aphase2study19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-門冬酰胺酶方案BLOOD,10FEBRUARY2011
VOLUME117,NUMBER6L-asparaginase6000u/m2d2、4、6、8immethotrexate3.0/m2d1

（>70歲2.0/m2)Dexamethas