NKT细胞淋巴瘤周剑峰.ppt

NK 细胞增殖性疾病细胞增殖性疾病 同济医院血液内科同济医院血液内科 周剑峰周剑峰 2015 年年06月月07日日 T 和和 NK 细胞肿瘤的分类：细胞肿瘤的分类：WHO 2008 WHO 2008:the mature T-cell and NK-cell neoplasms T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Chronic lymphoproliferative disorder of NK-cells*Aggressive NK cell leukemia Systemic EBV+T-cell lymphoproliferative disease of childhood(associated with CAEBV)Hydroa vacciniforme-like lymphoma Adult T-cell leukemia/lymphoma Extranodal NK/T cell lymphoma,nasal type Enteropathy-associated T-cell lymphoma Hepatosplenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides Szary syndrome Primary cutaneous CD30+T-cell lymphoproliferative disorder Lymphomatoid papulosis Primary cutaneous anaplastic large-cell lymphoma Primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma*Primary cutaneous gamma-delta T-cell lymphoma Primary cutaneous small/medium CD4+T-cell lymphoma*Peripheral T-cell lymphoma,not otherwise specified Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma(ALCL),ALK+Anaplastic large cell lymphoma(ALCL),ALK*2001 WHO 2008 WHO Comments Angioimmunoblastic Lymphoma Angioimmunoblastic Lymphoma Definition of origin cell Anaplastic Large Cell Lymphoma 2 variants based on ALK(+/-)expression Prognostic importance Unspecified Peripheral T-cell Lymphoma Peripheral T-cell Lymphomas not Otherwise Specified 3 variants:lymphoepitelioid lymphoma,T zone lymphoma(2001 WHO)and follicular lymphoma(2008 WHO)T/NK-cell lymphoma,nasal type T/NK-cell lymphoma,nasal type No changes Entheropathy-associated T-cell lymphoma Entheropathy-associated T-cell lymphomas Two variants:classical and monomorphic types with genetic changes common to both Hepatosplenic T-cell lymphoma Hepatosplenic T-cell lymphoma No changes Subcutaneous panniculitis-like T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Only ab and associated with autoimmune disorder Mycosis fungoides Mycosis fungoides New staging and new information about pathogenesis Szary syndrome Szary syndrome New markers Primary cutaneous anaplastic large cell lymphoma Primary cutaneous anaplastic large cell lymphoma Recognition of CD8+cases Lymphomatoid papulosis Lymphomatoid papulosis Three histological types Primary cutaneous gamma-delta T-cell lymphoma Three histopathologic patterns:epidermotropic,dermic,and subcutaneous subtypes Primary cutaneous CD8+aggressive epidermotropic cytotoxic T-cell lymphoma Provisional entity Primary cutaneous CD4+small/medium T-cell lymphoma Provisional entity Blastic NK-cell lymphoma Plasmocytoid dendritic cell neoplasm Now it is one of the myeloid neoplasms T-cell prolymphocytic leukemia T-cell prolymphocytic leukemia No changes T-cell large granular lymphocytic leukemia T-cell large granular lymphocytic leukemia New etiological features and new markers Chronic lymphoproliferative disorder of NK-cells Provisional entity Aggressive NK-cell leukemia Aggressive NK-cell leukemia No changes Adult T-cell leukemia/lymphoma Adult T-cell leukemia/lymphoma Definition of the regulatory T-cell normal counterpart T 和和 NK 细胞肿瘤分类的主要变化细胞肿瘤分类的主要变化 EBV 相关淋巴增殖性疾病相关淋巴增殖性疾病 J Korean Med Sci.2008 Apr;23(2):185-92.EBV 相关相关 T/NK 细胞增殖性疾病细胞增殖性疾病 J Dermatol.2014;41(1):29-39.潜伏性感染，不是裂解式感染，抗病毒治疗无效潜伏性感染，不是裂解式感染，抗病毒治疗无效 NK/T 细胞淋巴瘤细胞淋巴瘤 NK/T 细胞淋巴瘤亚型分布细胞淋巴瘤亚型分布 NK/T 细胞细胞淋巴瘤占到淋巴瘤占到所有所有 PTCL 的的10.4%J Clin Oncol,2008,26(25):4124-30 NK/T 细胞淋巴瘤特征细胞淋巴瘤特征 分为鼻型(68%)和非鼻型(26%),其他为侵袭型（6%）病理表现：形态多样，表现为血管中心性、大量坏死和血管浸润 表型：大部分为NK 细胞（EBV+，CD56+）鼻型与非鼻型鼻型与非鼻型 NK/T 细胞淋巴瘤细胞淋巴瘤 鼻型 非鼻型 侵犯部位 上呼吸 皮肤、睾丸、胃肠道 疾病晚期 27%68%肿块5cm 12%68%超过2个鼻外病灶 16%55%LDH升高 45%60%B症状 39%54%5年OS率 42%9%中位OS 19月 4月 鼻型与非鼻型鼻型与非鼻型 NK/T 细胞淋巴瘤细胞淋巴瘤 Nasal type:41%Non-nasal:22%Nasal type:34%Non-nasal:13%Ann Oncol 2008;19:1477-1484 放疗在放疗在 NK/T 细胞淋巴瘤中的地位细胞淋巴瘤中的地位 仅早期仅早期患者可作为根治手段患者可作为根治手段，其余多数与化疗联用，其余多数与化疗联用 什么样的什么样的 NK/T 细胞淋巴瘤可以单纯放疗细胞淋巴瘤可以单纯放疗？Nasal versus extra-nasal the stage of the disease Stage I disease are further stratified based on risk factors Age 60 years,B symptoms,ECOG performance status 2 Regional lymph node involvement Local tumor invasion Elevated LDH High Ki-67 staining EBV DNA 6.1 x 107 copies/mL 更新了治疗方案后，化疗是更新了治疗方案后，化疗是必不可少的治疗手段必不可少的治疗手段 局限期鼻型NK/T细胞淋巴瘤单纯放疗RR和CR分别达78-94%和 66-94%，但 5y-OS 和中位 OS仅分别为35%-83%和 50%患者出现皮肤、骨髓、睾丸、内脏和淋巴结侵犯较常见 化疗仍然是必不可少的治疗手段 NK/T 细胞肿瘤具有不同寻常的表型特征细胞肿瘤具有不同寻常的表型特征 含门冬酰胺酶的方案含门冬酰胺酶的方案 SMILE 方案方案 Smile方案 Steroid(DXM)40 mg,iv,d2-4 MTX 2 g/m2,iv,d1 IFO 1.5g/m2,iv,d2-4 L-ASP 6000U/m2,iv,d8,10,12,14,16,18,20 Etopside 100mg/m2,iv,d2-4 G-CSF 从第 6 天开始解救，wbc 5000/ml Yamaguchi M,et al.JCO,2011;29(33):4410-6 SMILE 方案疗效及毒性方案疗效及毒性 CR率45%,CR+PR 79%1y-OS 55%毒性反应：92%患者出现IV度骨髓抑制，61%出现感染 8%出现早期死亡 Yamaguchi M,et al.JCO,2011;29(33):4410-6 AspaMetDex 方案方案 Steroid（DXM）,40mg,d1-4,po MTX 3.0g/m2,d1,iv drip IFO 1.5g/m2,iv,d2-4 L-Asp 6000U/m2,d2,4,6,8,im Etopside 100mg/m2,iv,d2-4 Jaccard A,et al.Blood,2011,117:1834-1839.Smile方案 Steroid(DXM)40 mg,iv,d2-4 MTX 2 g/m2,iv,d1 IFO 1.5g/m2,iv,d2-4 L-ASP 6000U/m2,iv,d8,10,12,14,16,18,20 Etopside 100mg/m2,iv,d2-