结外NKT细胞淋巴瘤

结外NK/T细胞淋巴瘤,鼻型(ExtranodalNK/T-celllymphoma,nasaltype)福建省肿瘤医院

杨瑜1结外NKT细胞淋巴瘤5/9/2024未成熟NK细胞

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WHO-2008成熟NK细胞

：慢性NK细胞淋巴增殖性疾患侵袭性NK细胞白血病结外NK/T细胞淋巴瘤，鼻型2结外NKT细胞淋巴瘤5/9/2024

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3结外NKT细胞淋巴瘤5/9/2024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4结外NKT细胞淋巴瘤5/9/2024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T5结外NKT细胞淋巴瘤5/9/2024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6结外NKT细胞淋巴瘤5/9/20247结外NKT细胞淋巴瘤5/9/20248结外NKT细胞淋巴瘤5/9/20249结外NKT细胞淋巴瘤5/9/202410结外NKT细胞淋巴瘤5/9/202411结外NKT细胞淋巴瘤5/9/202412结外NKT细胞淋巴瘤5/9/2024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、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13结外NKT细胞淋巴瘤5/9/2024136例结外NK/T细胞淋巴瘤回顾性分析鼻的鼻外进展期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IntragumtornchaiT,etal.Blood2009;113:3931-3937.14结外NKT细胞淋巴瘤5/9/2024血中EBV-DNA与疾病过程？15结外NKT细胞淋巴瘤5/9/2024WholebloodEpstein-BarrvirusDNAloadasadiagnosticand

prognosticsurrogate:extranodalnaturalkiller/T-celllymphoma101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,May2009;50(5):757–76316结外NKT细胞淋巴瘤5/9/2024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,May2009;50(5):757–763(A)EBVloadsweresignificantlyassociatedwiththestage.(B)Usingthenewlyproposedmodel,patientsinriskgroups1–3(0–2riskfactors)hadalowerEBVDNAloadthanthoseinriskgroup4(3–4riskfactors).17结外NKT细胞淋巴瘤5/9/2024(C)PatientswhoattainedanobjectiveresponsealsohadasignificantlylowerEBVPCRload.(D)Patientswithextra-upperaerodigestivetractNK/T-celllymphomahadsignificantlyhigherEBVDNAloadthanpatientswithupperaerodigestivetractNK/T-celllymphoma.Leukemia&Lymphoma,May2009;50(5):757–76318结外NKT细胞淋巴瘤5/9/202419结外NKT细胞淋巴瘤5/9/2024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。20结外NKT细胞淋巴瘤5/9/2024预后指数21结外NKT细胞淋巴瘤5/9/2024ExtranodalNaturalKillerT-CellLymphoma,Nasal-Type:A

PrognosticModelFromaRetrospectiveMulticenterStudy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（Ⅲ/Ⅳ）区域淋巴结受累（N1-N3，非M1）分四个危险组：group1,nogroup2,onefactor;group3,twofactors;group4,threeorfourJClinOncol24:612-618.©2006byAmericanSocietyofClinicalOncology1

低危2低中危3

中高危4

高危22结外NKT细胞淋巴瘤5/9/202423结外NKT细胞淋巴瘤5/9/202424结外NKT细胞淋巴瘤5/9/2024group1：80.9%group2：64.2%group3：34.4%group4：6.6%5年OS25结外NKT细胞淋巴瘤5/9/2024IPI不能区分：低危与低中危

中高危与高危26结外NKT细胞淋巴瘤5/9/202476%0%27结外NKT细胞淋巴瘤5/9/2024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-PI28结外NKT细胞淋巴瘤5/9/2024治疗29结外NKT细胞淋巴瘤5/9/2024Treatmentoutcomeofradiotherapyaloneversus

radiochemotherapyinearlystagenasalnaturalkiller/T-cell

lymphomaEarlystage(stageIE:51,stageIIE:13)nasalNK/T-celllymphoma(NNTCL)23receivedradiotherapy(RT)alone,41casesweretreatedwithradiochemotherapy(RCT)1–6cyclesofanthracycline-basedchemotherapeuticregimens.MedOncol(2010)27:798–80630结外NKT细胞淋巴瘤5/9/202459.2%52.3%31结外NKT细胞淋巴瘤5/9/2024Fig.2Thesurvivalstatusofallpatientsaccordingtotreatmentmodality.(a)OS.(b)PFS.RTradiotherapyalone,RCTradiochemotherapy57.9%61.5%P=0.4732结外NKT细胞淋巴瘤5/9/2024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33结外NKT细胞淋巴瘤5/9/2024PhaseI/IIStudyofConcurrentChemoradiotherapyfor

LocalizedNasalNaturalKiller/T-CellLymphoma:Japan

ClinicalOncologyGroupStudyJCOG0211入组：33例新诊断局限期鼻的NK/T细胞淋巴瘤放疗剂量：ⅠE期50GY；ⅡE期50.4GY化疗方案：DeVIC3疗程登记入组后7天内同时开始JClinOncol27:5594-5600.©200934结外NKT细胞淋巴瘤5/9/2024Level1Level2DXM40mg40mgD1-3VP1667mg/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35结外NKT细胞淋巴瘤5/9/202436结外NKT细胞淋巴瘤5/9/2024Fig1.(A)Overallsurvivaland(B)progression-freesurvivalofpatientstreatedwithradiotherapyandtwothirdsdoseofdexamethasone,etoposide,ifosfamide,andcarboplatin.78%67%历史对照：单用放疗OS45%37结外NKT细胞淋巴瘤5/9/2024Fig2.Effectofcompleteresponse(CR)on(A)overallsurvivaland(B)progression-freesurvivalofpatientstreatedwithradiotherapyandtwothirdsdoseofdexamethasone,etoposide,ifosfamide,andcarboplatin.38结外NKT细胞淋巴瘤5/9/2024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Ⅰ、Ⅱ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39结外NKT细胞淋巴瘤5/9/2024PhaseIITrialofConcurrentRadiationandWeekly

CisplatinFollowedbyVIPDChemotherapyinNewly

Diagnosed,StageIEtoIIE,Nasal,ExtranodalNK/T-Cell

Lymphoma:ConsortiumforImprovingSurvivalof

LymphomaStudyJClinOncol27:6027-6032.©200930例新诊断ⅠE、ⅡE结外NK/T细胞淋巴瘤入组40结外NKT细胞淋巴瘤5/9/2024Fig2.Summaryoftreatmentoutcomesandtreatmentfailures.CCRT,concurrentchemoradiotherapy;CR,completeresponse;VIPD,etoposide,ifosfamide,cisplatin,anddexamethasone;PD,progressivedisease;PR,partialresponse.41结外NKT细胞淋巴瘤5/9/202442结外NKT细胞淋巴瘤5/9/20243年：PFS85.19%、OS86.28%43结外NKT细胞淋巴瘤5/9/202444结外NKT细胞淋巴瘤5/9/2024Inconclusion,CCRTfollowedbyVIPDchemotherapycanbeafeasibleandeffectivetreatmentstrategyforstagesIEtoIIEnasalENKTL.45结外NKT细胞淋巴瘤5/9/2024EfficacyofL-asparaginasewithmethotrexateanddexamethasone(AspaMetDex

regimen)inpatientswithrefractoryorrelapsingextranodalNK/T-celllymphoma,

aphase2study19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,10FEBRUARY2011
VOLUME117,NUMBER6L-asparaginase6000u/m2d2、4、6、8immethotrexate3.0/m2d1

（>70岁2.0/m2)Dexamethasone40mgd1-4

（>70岁20mg)21天，3疗程46结外NKT细胞淋巴瘤5/9/2024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：①3周期后对先前未放疗的局限性病灶予以防疗②对一般状况好的播散性病变予自体外周