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双语推荐：外周T/NK细胞淋巴瘤

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目的 统计中山大学肿瘤防治中心4年间诊断的所有成熟T和自然杀伤(NK)细胞淋巴瘤病例,分析其不同类型的构成比,研究各类型成熟T和NK细胞淋巴瘤CD30表达情况,为抗CD30抗体药物在成熟T和NK细胞淋巴瘤的应用提供参考数据.方法 选取2009年9月1日至2013年8月31日4年间中山大学肿瘤防治中心诊断的所有成熟T和NK细胞淋巴瘤,统计分析各类型淋巴瘤的发病情况.抽调其中存档的164例成熟T和NK细胞淋巴瘤患者的病理蜡块进行免疫组织化学EnVision法检测其CD30的表达.结果 4年间共诊断成熟T和NK细胞淋巴瘤625例.最常见为结外鼻型NK/T细胞淋巴瘤(ENKTL),共319例(51.0％),其余常见病例分别为血管免疫母细胞性T细胞淋巴瘤(AITL) 119例(19.0％)、非特指型外周T细胞淋巴瘤(PTCL-NOS)81例(13.0％)、间变性大细胞淋巴瘤(ALCL)[包括系统性ALCL 48例(7.7％)及原发皮肤ALCL 11例(1.8％)].除ALCL外,在本院存档的164例病例中,CD30阳性率最高的是NK/T细胞淋巴瘤,阳性率为62.1％(41/66).16例PTCL-NOS仅1例阳性,其余28例AITL及其他少见类型的淋巴瘤无1例阳性.结论 中山大学肿瘤防治中心收集的成熟T和NK细胞淋巴瘤不同类型的发病情况各异.CD30在多种成熟T和NK细胞淋巴瘤中均有不同程度表达,除间变性大
Objective To investigate the frequency of different types of mature T-and NK-cell lymphomas diagnosed in a 4-year period at Sun Yat-sen University Cancer Center,and to study baseline CD30 for potential anti-CD30 targeted therapy in mature T-and NK-cell lymphoma.Methods All cases of mature T-and NK-cell lymphoma diagnosed at Sun Yat-sen University Cancer Center from September 1,2009 to August 31,2013,were reviewed.Paraffin-blocks of available 164 consecutive cases were stained for CD30 immunohistochemistry using EnVision protocol.Results A total of 625 cases of mature T-and NK-cell lymphomas were diagnosed and the most common type was extranodal NK/T cell lymphoma (ENKTL),nasal type 319 (51.0％) cases,followed by angioimmunoblastic T-cell lymphoma (AITL) (119 cases,19.0％),peripheral T-cell lymphoma,not otherwise specified (PTCL-NOS) (81 cases,13.0％),and anaplastic large-cell lymphoma (ALCL),including 48 cases (7.7％) of systematic ALCL and 11 cases(1.8％) of primary cutaneou

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2008年版WHO淋巴瘤分类出版以来的数年中，淋巴瘤病理相关的知识又有所更新。对于B细胞非霍奇金淋巴瘤，人们较关注那些高度侵袭而又异质的亚型（例如：弥漫性大B细胞淋巴瘤），并努力尝试在分子生物学基础之上建立起更好的分型方法。此外，人们对于如何正确理解并处理明显的恶性淋巴瘤以及那些并不具有明确恶性行为、克隆性淋巴组织增生性疾病之间的“边界性”病变的兴趣也日益增长。另一方面，有关T和NK（T/NK）细胞的亚群构成、细胞分化方面的研究进展以及新近认识到的外周T/NK细胞淋巴瘤中的遗传学异常和信号路径调节失常，也有助于我们更深入地了解这些肿瘤的生物学特性。临床惰性、克隆性T/NK细胞增生性病变、特别是发生于黏膜皮肤部位者，也愈发受到人们关注。这些新的知识进展会推动淋巴瘤分类不断向前演进。
Updated knowledge about lymphoma pathology has been accumulated ever since the publication of the current WHO classiifcation of lymphomas in 2008. For B-cell non-Hodgkin lymphomas, endeavors have been made for approaching a better classiifcation of those highly aggressive and heterogeneous subtypes (e.g., diffuse large B-cell lymphomas) on the molecular biological basis. In addition, there is a growing interest in understanding and deal-ing with the borders of overt malignant lymphomas and certain clonal lymphproliferative disorders that are not overtly malignant. On the other hand, recent advances in understanding the subsets of T and NK (T/NK)-cell lineage and their differentiation, as well as the genetic aberrations or dysregulated signaling pathways in their neoplastic counterparts, have provided us novel insights into the biology of peripheral T/NK-cell lymphomas. Indolent clonal T/NK-cell prolif-erations, especially those arising from the mucocutaneous sites, have also

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目的：探讨滤泡树突状细胞（follicular dendritic cell，FDC）网在各种类型淋巴瘤中的形态变化模式及其在鉴别诊断中的临床应用价值。方法采用免疫组化方法对56例各种类型的淋巴瘤进行 CD21免疫组化染色，观察 FDC网的形态变化模式。其中包括弥漫大B细胞淋巴瘤8例、伯基特淋巴瘤2例、小淋巴细胞性淋巴瘤6例、浆细胞瘤6例、MALT淋巴瘤3例、外周T细胞淋巴瘤6例、间变性大细胞淋巴瘤5例、NK／T细胞淋巴瘤8例、滤泡性淋巴瘤4例、套细胞淋巴瘤3例、AITL 3例、FDC肉瘤 2例。结果 FDC网在各种类型淋巴瘤中的形态变化可归为4种模式：①破坏消减型：绝大部分淋巴瘤 FDC网完全或部分破坏，包括弥漫大B细胞淋巴瘤、伯基特淋巴瘤、小淋巴细胞性淋巴瘤、浆细胞瘤、外周 T细胞淋巴瘤、间变性大细胞淋巴瘤、NK／T细胞淋巴瘤；②存在型：FDC网存在，甚至有数量增多，包括MALT淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤；③增生紊乱型：FDC网增多、变形、紊乱，如 AITL；④全表达型：FDC网在肿瘤组织中每个细胞表达，如 FDC肉瘤。结论 FDC在各种类型淋巴瘤中存在不同的形态变化模式，在淋巴瘤鉴别诊断中具有重要的临床应用价值。
Objective To explore the differentiated diagnostic value of the morphological changes of follicular dendritic cell (FDC)meshwork between different subtype of lymphoma.Methods CD21 was stained by immunohistochemistry (IHC) method,FDC meshwork pattern was studied in 5 6 cases of various lymphomas(including 8 cases of diffuse large B cell lym-phoma,2 cases of burkitts lymphoma,6 cases of small lymphocytic lymphoma,6 cases of plasmacytoma,3 cases of MALT lymphoma,6 cases of peripheral T cell lymphoma,3 cases of anaplastic large cell lymphoma,8 cases of NK/T cell lympho-ma,4 cases of follicular lymphoma,3 cases of mantle cell lymphoma,3 cases of AITL,2 cases of FDC sarcoma).Results FDC meshwork in the morphological changes of various subtypes of lymphoma could be classified into four patterns:①FDC form a disappeared and disintegrated meshwork,most of the lymphoma FDC meshwork fully or partially destroyed,including diffuse large B cell lymphoma,burkitt lymphoma,small lymphocytic l

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2012年的第54届美国血液学会(ASH)年会对于淋巴瘤而言或许具有“革命性”的意义,会议上首次明确提出“远离化疗”治愈淋巴瘤的梦想.而这一观点的提出并非凭空想象.随着对淋巴瘤本质的认识愈加深入,针对淋巴肿瘤细胞表面抗原、细胞内信号转导通路和细胞微环境的靶向药物的研发已取得明显进展.特别是针对惰性B细胞淋巴瘤的靶向药物组合在临床研究中已显示出超越传统化疗方案联合靶向药物的疗效,而且安全性更好.靶向治疗在侵袭性B细胞淋巴瘤和外周T/NK细胞淋巴瘤方面也显示了良好的前景,相信不久的将来定能有所突破.
The 54th ASH annual meeting should be considered as a revolution for treatment of lymphoma."Keep away from chemotherapy" will not be just a dream,it based on the deep understand of lymphoma genesis and quick development of different targeted agents.The typical examples are the dramatic novel agents targeting B cell receptor signaling pathway and microenvironment.There combination,such as R-square regimen,showed unbelievable efficacy in indolent B cell lymphomas and tiny side effects.It is sure that therapy breakthroughs in aggressive B cell lymphomas and T/NK cell lymphomas are in the very near future.

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目的探讨儿童非霍奇金淋巴瘤(NHL)临床特点及预后相关因素。方法选取本院收治的NHL患儿63例,按照WHO淋巴瘤分型标准进行诊断,根据不同免疫标记、病理分型、临床分期进行化疗。采用Kaplan-Meier法进行生存分析,不同临床因素的生存率比较采用卡方检验。结果 T淋巴细胞母细胞淋巴瘤(T-LBL)19例(30%),B淋巴细胞母细胞淋巴瘤(B-LBL)5例(7.9%),Burkitt''s淋巴瘤(BL)16例(25.4%),弥漫性大B细胞淋巴瘤(DLBCL)9例(14.3%),滤泡性淋巴瘤(FL)1例(1.6%),黏膜相关性淋巴组织淋巴瘤(MALT)1例(1.6%),间变大细胞性淋巴瘤(ALCL)5例(7.9%),外周T细胞淋巴瘤-非特异型(PTCL-NOS)2例(3.2%),皮下脂膜炎样T细胞淋巴瘤(SPTCL)2例(3.2%),NK/T细胞淋巴瘤2例(3.2%),系统性EBV+儿童T细胞淋巴组织增殖性疾病(CSEBV+T-LPD)1例(1.6%)。Ⅰ期3例(4.8%),Ⅱ期7例(11.1%),Ⅲ期18例(28.6%),Ⅳ期35例(55.6%)。1年总生存率(OS)为80.95%,3年OS为73.02%。3年无复发生存率(RFS)为68.85%,5年RFS为66.13%。单因素分析提示存在中枢神经系统浸润及血LDH升高影响预后。结论儿童NHL不同病理类型的预后存在差异。应根据病理诊断、临床分期及各种危险因素的评估,实施不同强度和疗程的化疗方案,以达到更好治疗效果。
Objective To evaluate the clinical characteristics of childhood non-Hodgkin’ s lymphoma and prognostic factors. Method From October 2005 to January 2014,63 children newly diagnosed with NHL were included in the study accordins to the World Health Organization classification of tumors. The chemotherapy regimens were based on immunephenotype、pathological type and clinical stages. The rate of overall survival( OS) and relapse-free survival ( RFS) were analyzed by Kapkn-Meier, The survival rate of different clinical factors were compared using the chi-square test. Result Among 63 cases, 19 cases ( 30%) were T-LBL, 5 cases ( 7. 9%) were B-LBL, 16 cases (25. 4%) were BL,9 cases(14. 3%) were DLBCL,1 case(1. 6%) was FL,1 case(1. 6%) was MALT,5 cases (7. 9%) were ALCL,2 cases(3. 2%) were PTCL-NOS,2 cases(3. 2%) were SPTCL,2 cases(3. 2%) were NK/T cell lymphom,1 case(1. 6%) was CSEBV+T-LPD. 3 cases were divided into stage Ⅰ,7 cases into stage Ⅱ,18 cases into stage Ⅲ and 35 cases i

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目的 通过检测鼻型结外NK/T细胞淋巴瘤(ENKL)患者外周血调节性T细胞(Treg细胞),探讨外周血Treg细胞与ENKL的关系.方法 选取北京同仁医院血液科2009年3月至2012年12月收治的41例初治ENKL患者,20名健康志愿者作为正常对照.采用流式细胞仪联合标记检测外周血Treg(CD4+CD25+)细胞,并与淋巴瘤危险因素及疗效、预后等进行相关性分析.结果 ENKL患者治疗前外周血Treg细胞比例为(9.64±4.96)％,高于正常对照组的(7.31±3.02)％,差异具有统计学意义(P＜0.05);治疗后患者外周血Treg细胞降至(5.18±2.19)％,与治疗前比较差异具有统计学意义(P＜0.01);Treg细胞比例在治疗有效组(35例)和治疗无效组(6例)分别为(8.79±4.15)％和(14.57±6.73)％,两者差异具有统计学意义(P＜ 0.05).ENKL患者Treg细胞比例与血清LDH水平呈正相关;Treg细胞比例正常组患者的总生存率和无进展生存率高于Treg细胞比例增高组,但差异无统计学意义.结论 ENKL患者外周血Treg细胞与疗效及血清LDH水平相关,可能对ENKL的疗效及预后有一定的预测作用.
Objective To investigate the clinical significance of peripheral blood regulatory T cell (Treg) population in patients with extranodal NK/T cell lymphoma,nasal type (ENKL).Methods The peripheral blood CD4+CD25+ Treg cell population was detected by flow cytometry in 41 newly diagnosed ENKL patients between March 2009 and December 2012.Results The proportion of CD4+CD25+ Treg cell population increased in ENKL patients compared to healthy donors [(9.64±4.96) ％ vs (7.31 ± 3.02) ％,P＜0.05],and decreased significantly after treatment [(5.18 ±2.19) ％,P＜0.01].Patients when got response had significantly lower proportion of Treg cells [(8.79±4.15)％] as compared with those without response [(14.57±6.73)％,P＜0.05].The proportion of Treg population was positively related to the serum lactate dehydrogenass level.Conclusions The proportion of peripheral blood Treg cells may be helpful for predicting prognosis and therapeutic efficacy in ENKL patients.

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细胞因子诱导的杀伤细胞(CIK细胞)是人类外周血单个核细胞(PBMC)在体外经干扰素-γ、抗CD3单克隆抗体、白细胞介素(IL)-2、IL-1等诱导培养而获得的一种新型免疫活性细胞.CIK细胞具有T细胞和NK细胞的双重表面标志,在体内外拥有强大的抗肿瘤活性,且兼有非主要组织相容性复合体(MHC)限制性的优点,是目前过继免疫治疗肿瘤的主要效应细胞,已被广泛应用于肝癌、肺癌等实体瘤及白血病、淋巴瘤、骨髓瘤等血液系统肿瘤的辅助治疗.文章就CIK细胞的优化培养及在血液系统恶性肿瘤治疗中的应用进展作一综述.
Cytokine induced killer (CIK) cells are a new kind of cytotoxic cells,which are generated by stimulation of peripheral blood mononuclear cells (PBMC) with IFN-γ,IL-2,IL-1 and anti-CD3 in vitro.These cells represent phenotype of both T cell and NK cell and have advantages of the non MHC restriction,so they have a strong ability of antitumor activity in vivo and vitro.Now,CIK cells as the main effector cells of adoptive immunotherapy have been extensively used in a variety of solid tumors such as liver cancer,lung cancer and hematological malignancies including leukemia,lymphoma,myeloma.In this article,the optimized cultivation of CIK cells as well as their most prominent clinical application in hematologic malignancies were summarized.

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外周T/NK细胞淋巴瘤(PT/NKCLs)是一组高度异质性的T/NK细胞恶性肿瘤,在全球平均发病率低,具有明显的地域和种族差异性,亚洲人群相对高发,病理亚型差异性更显著,也是影响预后的最关键因素。目前治疗以CHOP类方案为主,因此初治高危的侵袭性PTCLs、二线挽救化疗有效的复发难治患者,均应考虑大剂量化疗联合造血干细胞移植,自体干细胞移植仍然作为首选。新的化疗药物,如Pralatrexate、苯达莫司汀等,对复发难治的PTCLs有效率约30%。靶向药物包括单抗类药物、针对细胞内信号传导通路的小分子抗体药物以及免疫调节药物,也在不同亚型PTCLs中取得一定疗效。本综述对PT/NKCLs诊治现状做一总结。
The peripheral T/NK cell lymphomas (PT/NKCLs) encompass a heterogeneous group of malignant lymphoid diseas-es, which derived from mature T-cells and NK cells. PT/NKCLs are rare, and its epidemiology and pathological subtypes showed signif-icant geographic and ethnic differences. PT/NKCLs, especially NK/T cell lymphoma (nasal type), are relatively common in Asian coun-tries. The use of an anthracycline-containing regimen is not associated with an improved outcome in most subtypes of PT/NKCLs, but is associated with an improved outcome in anaplastic large-cell lymphoma, ALK positive. High-dosage chemotherapy combined with stem cell transplantation is a considerable choice for newly diagnosed high-risk or refractory/relapsed PT/NKCLs because of its general-ly poor clinical outcome. Advances in new drugs have lagged behind DLBCL because of the disease rarity of PT/NKCL and biological heterogeneity. Nevertheless, new chemotherapeutic drugs, such as pralatrexate and bendamustine, a

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目的：探讨非霍奇金淋巴瘤（ NHL ）免疫功能的变化及其临床意义。方法初治NHL患者50例为实验组，采集静脉血检测T细胞亚群、NK细胞及免疫球蛋白（ Ig）水平，与30名健康对照者进行比较；并对50例患者中不同临床分期、有无B症状及治疗有效无效组进行比较。结果实验组外周血CD4＋、 NK细胞计数及CD4＋／CD8＋比值均明显低于对照组（P＜0．05），实验组与对照组的CD3＋、CD8＋、CD19＋计数比较差异无统计学意义（ P＞0．05）；实验组中，治疗无效组、有B组症状组、Ⅲ＋Ⅳ期组的CD4＋、NK细胞计数及CD4＋／CD8＋比值明显降低（P＜0．05）；实验组与对照组及实验组各亚组间的IgA、IgG 、IgM水平比较，差异均无统计学意义（P＞0．05）。结论 NHL患者存在细胞免疫抑制，其临床分期、治疗疗效与细胞免疫功能有关，而与体液免疫的相关性有待进一步探讨。
Objective To investigate the changes of immune function in patients with non-Hodgkin′s lymphoma ( NHL) and its clinical significance .Methods Fifty newly diagnosed NHL patients ( experimental group ) were enrolled in this study and 30 healthy adults served as control .Their venous blood samples were collected to detect the levels of T lymphocyte subsets ,NK cells and immunoglobulin ( Ig ) .The comparative analysis was conducted among patients with different clinical stages ,with B symptoms or not ,and with different curative effects .Results The levels of CD4+,NK cells,CD4+/CD8+of experimental group were significantly lower than those of control group (P 0.05).In the experimental group ,the levels of CD4+,NK cells ,CD4+/CD8+decreased significantly in the uncured patients ,patients with B symptoms,and patients of stageⅢorⅣ(P 0 .05 ) . Conclusion The cellular immune response is suppressed in patients with NHL,and the suppression is correlated with clinical stage,B symptoms a

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鼻型结外NK/T细胞淋巴瘤(ENKTL)是来源于NK细胞或T细胞的一种侵袭性淋巴瘤,预后较差.文章主要论述造血干细胞移植在该病治疗中的地位.
Extranodal NK/T-cell lymphoma,nasal type (ENKTL) is a aggressive lymphoma which arises from NK cells or T cells and has a poor prognosis.This article mainly reviewed and focused on hematological stem cell transplantation in treating ENKTL.

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