伴有二次打击的弥漫大B细胞淋巴瘤研究进展

弥漫大B细胞淋巴瘤（DLBCL）是一种异质性很大的非霍奇金淋巴瘤,其中同时伴有myc和bcl-2重排（或bcl-6重排）者是一种较少见的类型,被称作二次打击淋巴瘤.其临床表现为明显的侵袭性、对化疗耐药、预后极差,成为近年来研究的热点.文章探讨了伴有二次打击的DLBCL重排基因的功能、临床特征、诊断及治疗.     

Hyper—CVAD／MA方案治疗28例中国人非霍奇金淋巴瘤的有效性及安全性

目的评估Hyper-CVAD／MA强化方案治疗28例中国人T细胞性和侵袭性／高度侵袭性B细胞性非霍奇金淋巴瘤患者的有效性和安全性。方法回顾性分析28例2005年1月至2008年9月用Hyper—CVAD／MA方案治疗的初治或复治的B细胞或T细胞非霍奇金淋巴瘤患者的有效性和安全性。结果在27例可评价疗效的包括T细胞和B细胞淋巴瘤的病例中,有效率是70．4％;在13例可评价疗效的B细胞淋巴瘤中,有效率是84．6％。27例患者均发生Ⅲ度或Ⅳ度的骨髓抑制,有2例治疗相关死亡。结论Hyper—CVAD／MA方案治疗中国人T细胞性和侵袭性／高度侵袭性B细胞性非霍奇金淋巴瘤,有效率高,但毒副作用也显著,剂量需要进一步摸索。     

侵袭性B细胞淋巴瘤中PIK3CA扩增和PTEN缺失及其临床病理学意义

  目的  探讨侵袭性B细胞淋巴瘤在PI3K/Akt/mTOR信号通路中PIK3CA与10号染色体上缺失的磷酸酶和张力蛋白同源物（phosphate and tension homology deleted on chromsome ten,PTEN）的表达情况及其与各临床病理指标的相关性。  方法  回顾性分析新疆医科大学第一附属医院2008年1月至2012年12月术前未经任何治疗的侵袭性B细胞淋巴瘤标本235例,其中包括弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）205例,伯基特淋巴瘤（Burkitt lymphoma,BL）27例,灰区淋巴瘤（介于DLBCL和BL之间,不能分类的B细胞淋巴瘤）3例。应用荧光原位杂交技术检测所有样本PIK3CA和PTEN基因的表达情况,统计分析其与各临床病理指标及预后的关系。  结果  PIK3CA在侵袭性B细胞淋巴瘤中扩增率为12.3%（29/235）,临床分期Ⅰ~Ⅱ期和Ⅲ~Ⅳ期的阳性率分别为8.6%（12/139）和17.7%（17/96）,差异具有统计学意义（P=0.038）。PTEN在侵袭性B细胞淋巴瘤中的缺失率为13.6%（32/235）,与其他临床病理特征无相关性。PIK3CA扩增和PTEN缺失呈负相关（P=0.046）。未发现PIK3CA扩增和PTEN缺失与生存期存在相关性。  结论  PIK3CA扩增与侵袭性B细胞淋巴瘤疾病晚期相关,PIK3CA扩增和PTEN缺失在侵袭性B细胞淋巴瘤的发生中起促进作用。      

纵隔灰区淋巴瘤的研究进展

 纵隔灰区淋巴瘤（mediastinal gray zone lymphoma）作为一个疾病实体,常不能依据现有的诊断标准进行分类。这类淋巴瘤同时具有纵隔弥漫大B细胞淋巴瘤（PMBL）和经典霍奇金淋巴瘤（cHL）的特征。在2008年WHO造血与淋巴组织肿瘤分类中将其命名为“B细胞淋巴瘤,不能分类,具有介于弥漫大B细胞淋巴瘤和经典霍奇金淋巴瘤之间的特征（BCLu）”。BCLu具有独特的临床特点、免疫表型和分子遗传学特征,临床过程更具侵袭性,预后较差。目前尚无达成共识的治疗方案,可参照侵袭性B细胞淋巴瘤的方案化疗。     

侵袭性非霍奇金淋巴瘤治疗进展

研究表明持续给药方式和新型靶向药物有望改善侵袭性B细胞淋巴瘤患者的预后,加大化疗药物剂量未显示疗效提高.侵袭性T细胞淋巴瘤患者的预后近些年有所改善,归因于自然杀伤细胞/T细胞淋巴瘤化疗方案的改进.多发遗传学异常是侵袭性T细胞淋巴瘤不良预后的内因,非清髓性异基因造血干细胞移植和新型靶向药物提示增加治疗疗效.现代放疗技术也是提高侵袭性非霍奇金淋巴瘤疗效的重要手段.     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

血管内大B细胞淋巴瘤研究进展

 血管内大B细胞淋巴瘤（IVLBCL）是弥漫性大B细胞淋巴瘤（DLBCL）的一种罕见亚型,病理改变以血管腔内淋巴瘤细胞的异常增殖为特征,临床上具有侵袭性强、预后不佳及生存期短等特点。现就近年来IVLBCL的分型、诊断、治疗以及预后等方面的研究进展进行综述。     

套细胞淋巴瘤诊治进展

套细胞淋巴瘤（MCL）是小 B 细胞淋巴瘤中一组高侵袭性的非霍奇金淋巴瘤（NHL）,约占NHL 的6%。MCL 起病隐匿、侵袭性强、恶性程度高、预后差,因此,MCL 的诊断及鉴别诊断至关重要。另外,MCL 分子病理模型、细胞周期蛋白 D1阴性 MCL、MCL 分期预后及分层治疗选择均值得关注。     

造血干细胞移植在鼻型结外NK/T细胞淋巴瘤治疗中的地位

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.     

血管免疫母细胞性T细胞淋巴瘤患者EB病毒感染情况及其临床意义

目的 探讨血管免疫母细胞性T细胞淋巴瘤患者的EB病毒感染情况及其临床病理学意义.方法 回顾性分析2008年1月至2011年12月经常规外检及会诊确诊的血管免疫母细胞性T细胞淋巴瘤62例,进行常规形态学和免疫学表型分析,采用原位杂交方法检测EB病毒编码小RNA（EBV-EBER）的表达情况,并随访患者.结果 62例血管免疫母细胞性T细胞淋巴瘤患者中,EBV-EBER阳性者26例（42％）.EBV-EBER表达与患者年龄大于60岁以及治疗反应密切相关（P=0.025、0.049）,而与患者的总体生存时间、临床B症状及Ann Arbor分期无关（均P＞0.05）.结论 血管免疫母细胞性T细胞淋巴瘤患者EB病毒感染不影响总体生存时间,但影响患者对治疗的反应.     

套细胞淋巴瘤治疗进展

套细胞淋巴瘤是具有独特生物学、病理和临床特征的B细胞恶性肿瘤，占非霍奇金淋巴瘤5%~10%，大多数患者诊断时即为晚期。套细胞淋巴瘤具有侵袭性淋巴瘤的侵袭性和惰性淋巴瘤的难治愈性特征，患者预后较差。近年来随着大剂量化疗、自体造血干细胞移植及新药研究的进展，患者生存期得到明显延长。     

CAR T-cell therapy for B-cell lymphoma

Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.     

复发难治性弥漫大B细胞淋巴瘤的生物靶向治疗

含有利妥昔单抗的化疗方案能改善弥漫大B细胞淋巴瘤(DLBCL)患者的预后,然而仍有部分患者在一线应用R-CHOP方案后转为复发难治性DLBCL(RR-DLBCL),且预后不良.对DLBCL及其相关肿瘤基因表达研究证实基因水平的生物靶向治疗能改善RR-DLBCL患者的预后.目前,一些新的靶向治疗成为研究热点.文章就RR-DLBCL的生物靶向治疗进展进行综述.     

Primary cutaneous B-cell lymphoma: classification and treatment

PURPOSE OF REVIEW: There has been confusion and debate regarding the definition, terminology, and optimal treatment of the different types of primary cutaneous B-cell lymphomas. This review presents the new World Health Organization-European Organization for the Research and Treatment of Cancer classification for cutaneous lymphomas; describes clinicopathologic, immunophenotypic, and genetic features of the different types of cutaneous B-cell lymphomas in this classification; and discusses current views on treatment of these lymphomas. RECENT FINDINGS: The three main types of cutaneous B-cell lymphomas in this new classification are primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous large B-cell lymphoma (leg type). Primary cutaneous marginal zone B-cell and primary cutaneous follicle center lymphoma are indolent types with an excellent prognosis that should be treated primarily with nonaggressive therapies. Primary cutaneous large B-cell lymphoma (leg type) is an aggressive lymphoma that should be treated primarily with aggressive chemotherapy. SUMMARY: The World Health Organization-European Organization for the Research and Treatment of Cancer classification will contribute to uniform diagnosis, management, and treatment of patients with cutaneous B-cell lymphoma and will prevent patients with indolent types of the disease from being treated inappropriately with systemic chemotherapy.     

An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab.

The chimeric anti-CD20 monoclonal antibody rituximab has become part of the standard therapy for patients with non-Hodgkin's lymphoma (NHL). To date, more than 300 000 patients have been treated with rituximab worldwide, including patients with indolent and aggressive NHL, Hodgkin's disease and other B-cell malignancies. Combination of rituximab with cytotoxic agents or cytokines has been explored in a number of different studies. Rituximab is now also approved for patients with diffuse large B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone). The monoclonal antibody is generally well tolerated. Most adverse events are infusion-associated, including chills, fever and rigor related to the release of cytokines.     

利妥昔单抗联合高剂量治疗和自体外周血干细胞移植治疗侵袭性B细胞淋巴瘤的多中心前瞻性研究

目的 探讨在高剂量治疗联合自体外周血干细胞移植的基础上,加用利妥昔单抗治疗侵袭性B细胞淋巴瘤的可行性和疗效.方法 12个癌症研究中心共入组28例侵袭性B细胞淋巴瘤患者,其中22例为新诊断患者,6例为复发患者.每例患者共接受4次利妥昔单抗静脉输注,即在外周血干细胞动员化疗的前1天、动员化疗的第7天、干细胞回输的前1天和回输后的第8天各给予1次,每次375 mg/m2,共1500 mg/m2结果 高剂量治疗后,所有患者均达到完全缓解.中位随访37个月时,全组患者的4年总生存率和无进展生存率分别为75.0%和70.3%,新诊断患者的4年总生存率和无进展生存率均为72.7%.全组患者对利妥昔单抗治疗的耐受性较好,不良反应多为1、2度.结论 在高剂量治疗联合自体造血干细胞移植的基础上加入利妥昔单抗治疗侵袭性B细胞淋巴瘤是可行的,并且可能使患者的生存获益.     

靶向药物治疗套细胞淋巴瘤的研究进展

套细胞淋巴瘤(MCL)是一种少见的非霍奇金淋巴瘤亚型.MCL临床表现有两种类型:一种为惰性表现,病情进展缓慢;另一种为侵袭性表现,病程进展迅速.近年,一些用于MCL治疗的新靶向药物已经问世.这些靶向药物较常规化疗提高了对复发/难治性MCL的疗效,其治疗MCL的靶点为B细胞淋巴瘤表面抗原、B细胞受体信号和肿瘤细胞微环境等.文章介绍了MCL靶向药物的研究进展.     

侵袭性B细胞淋巴瘤新的标准治疗方案

实施CHOP方案(环磷酰胺、阿霉素、长春新碱和泼尼松)治疗20多年来,侵袭性B细胞淋巴瘤已成为可治愈的疾病,CHOP方案也已成为治疗这一疾病的标准方案。但其治愈率只有35%~40%,半数以上复发。随着抗B细胞表面抗原CD20的人鼠嵌合型单克隆抗体利妥昔(rituximab)的应用,侵袭性B细胞淋巴瘤的治疗已发生了根本改变。多项大型Ⅲ期随机临床研究结果证实,利妥昔与CHOP方案或CHOP样方案联合应用,比单纯联合化疗能明显改善侵袭性B细胞淋巴瘤的有效率,无事件生存和长期生存结果,无论是老年或年轻患者,低危预后还是高危预后患者,均有显著的统计学差异。因此,利妥昔加CHOP或CHOP样方案的联合治疗已成为侵袭性B细胞淋巴瘤新的标准治疗方案。     

Advances in the treatment of aggressive non-Hodgkin's lymphoma

As recent researches suggested, the continuous infusion and novel targeted medicines have been expected to improve the outcome of patients with aggressive B-cell non-Hodgkin's lymphoma. Nevertheless, it does not shown to improve the curative effect by increasingly intensive dosage. Patients with aggressive T-cell non-Hodgkin's lymphoma have present better prognosis recently, which attributed to better efficacy of the modified regimens in patients with NK/T cell lymphoma. Multiple genetic abnormalities are implicated in poorer prognosis in patients with aggressive T-cell non-Hodgkin's lymphoma. Non-myeloablative allogeneic stem cell transplantation and new targeted drugs have showed to improve the curative effects. Radiotherapy with modern technology also is expected to become an important means to improve outcomes of aggressive non-Hodgkin's lymphoma.