原发纵隔大B细胞淋巴瘤的治疗进展

摘 要：原发纵隔大B细胞淋巴瘤（primary mediastinal large B-cell lymphoma，PMBCL）是来源于胸腺髓质B细胞的恶性肿瘤，属于弥漫大B细胞淋巴瘤的特殊亚型。由于发病率低，缺乏大样本前瞻性临床研究，目前PMBCL尚无统一的治疗方案，主要治疗方式包括化疗、放疗、自体干细胞移植及靶向治疗等。PMBCL具有特殊的分子生物学特征，这一特点为其特征性的治疗提供了重要参考。全文将主要就PMBCL的治疗进展作一综述。     

原发纵隔B细胞淋巴瘤研究进展

 【摘要】　新的WHO分类将原发纵隔B细胞淋巴瘤（PMBCL）归为弥漫大B细胞淋巴瘤（DLBCL）的一个独立亚型,其在发病机制、病理组织学、分子遗传学及临床特点等多个方面均与其他类型的DLBCL有所不同,与霍奇金淋巴瘤及纵隔灰区淋巴瘤又有着密切地联系,为加深临床医师对PMBCL的认识,就近年来的相关研究进行综述。     

原发纵隔淋巴瘤研究进展：第19届欧洲血液学会年会报道

原发纵隔大B细胞淋巴瘤（PMBCL）是一种特殊类型的B细胞淋巴瘤,推测来源于胸腺髓质B细胞,占所有弥漫大B细胞淋巴瘤（DLBCL）的6％～10％,具有特殊的病理特征、免疫表型和基因异常,需要与经典型霍奇金淋巴瘤和其他结性DLBCL亚型鉴别.文章就PMBCL的病理学特征、分子生物学改变、治疗、预后及正电子发射型计算机断层扫描显像（PET）在评估初始治疗反应中的作用进行介绍.     

原发性纵隔大B细胞淋巴瘤研究进展

 原发性纵隔大B细胞淋巴瘤（PMBCL）是弥漫大B细胞淋巴瘤（DLBCL）的一种特殊类型，具有独特的临床表现及病理学、分子生物学特征。目前尚无标准的治疗方案，回顾性分析表明第三代的化疗方案优于CHOP方案，利妥昔单抗的应用缓解了这种差异，是否需要接受联合放疗尚无定论。未来将脱氧葡萄糖-正电子发射计算机断层显像（FDG-PET）用于PMBCL的疗效评估，如果能提供可靠的预后信息，就可以减轻治疗强度。     

原发纵隔B细胞淋巴瘤研究进展

原发纵隔B细胞淋巴瘤(PMBCL)属于非霍奇金淋巴瘤中的独立病理类型.PMBCL是一种高度侵袭性B细胞淋巴瘤,患者有独特的临床表现:好发于年轻人及女性,多数患者就诊时处于Ⅰ～Ⅱ期,大纵隔、大肿块多见.PMBCL缺乏相应随机临床试验,多数PMBCL患者接受化疗后加巩固性累及野放疗(IF-RT)的治疗方式,认为巩固放疗能提高PMBCL患者的完全缓解率和无复发生存率,用化放疗综合治疗取得了较好疗效.不同肿瘤治疗与研究中心采用的临床化疗方案不同,主要化疗方案包括CHOP、CHOP类似方案、高强度化疗方案或三代化疗方案.最近一些临床研究结果显示,利妥昔单抗和蒽环类化疗方案提高了治疗效果,改善了患者预后,生存率有升高趋势.在利妥昔单抗治疗时代,巩固性IF-RT仍然起重要作用,尤其是对于治疗前有大肿块患者,近期文献报道放疗显著提高了局部控制率.PMBCL中调强放疗靶区剂量分布更均匀,预后更好,正常组织剂量限制更精确,治疗相关毒性更小.多数肿瘤治疗研究中心采用化疗后巩固放疗的综合治疗方案.利妥昔单抗与放疗对PMBCL患者预后是否有重要影响迄今为止没有明确的结论.PMBCL治疗方案目前鲜见前瞻性随机对照研究,值得进行进一步大样本随机临床研究.     

放化疗与单纯化疗对原发纵隔大B细胞淋巴瘤患者生存的影响比较

目的 探讨原发纵隔大B细胞淋巴瘤(PMBCL)的预后影响因素,分析利妥昔单抗时代前后接受放化疗与单纯化疗对患者预后的影响.方法 从SEER数据库中提取2001—2015年间确诊的PMBCL患者,SEER Stat软件计算PMBCL的发病率,Kaplan-Meier法和Cox回归模型分析各临床变量对预后的影响.结果 排除...     

利妥昔单抗应用于临床后原发纵隔B细胞淋巴瘤治疗进展

原发性纵隔B细胞淋巴瘤(PMBCL)形态学上与弥漫性大B细胞淋巴瘤(DLBCL)和结节性硬化霍奇金淋巴瘤相似。多数 PMBCL 患者接受化疗后加巩固性累及野放疗治疗方式,认为巩固放疗能提高PMBCL的有效率和PFS,化放疗结合取得了较好疗效。最近临床研究结果显示,利妥昔单抗和蒽环类化疗方案提高了PMBCL治疗效果,能降低早期治疗失败,提高PFS和OS,改善预后。利妥昔单抗结合部分高强度化疗后不放疗也取得了较好疗效,但多数文献仍在支持免疫化疗后巩固性纵隔放疗。基于病例数较少的研究结果,结合PET进展高强度免疫化疗后PET评价达到完全代谢缓解(CMR)的患者,或许可以不行巩固纵隔放疗。然而,这些结果需要一系列更大样本的多中心临床试验证实,患者伴预后不良因素或PET评价分值高于3分时建议纵隔巩固性放疗。     

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。     

24例原发纵隔大B细胞淋巴瘤的临床分析并文献复习

背景与目的:原发纵隔大B细胞淋巴瘤(primary mediastinal large B-cell lymphoma,PMBCL)是弥漫大B细胞淋巴瘤的一种亚型,发病率较低。本研究旨在分析其临床特征,探讨合理的治疗模式及预后因素。方法:收集1995年5月至2005年9月于福建省肿瘤医院确诊并接受治疗的24例PMBCL患者的临床资料并行回顾性分析,同时结合文献加以讨论。结果:24例患者中男性16例,女性8例,年龄12～81岁,30岁以下13例。临床Ⅰ Ⅱ期20例,Ⅲ期1例,Ⅳ期3例。有纵隔巨块13例,伴上腔静脉综合征10例,邻近器官受侵14例,乳酸脱氢酶升高15例。初治时11例采用联合化放疗,10例采用单纯化疗,3例采用单纯放疗,完全缓解率41.7%,总有效率91.7%,中位生存期89个月,3年总生存率68.8%,其中初治时达完全缓解者至随访结束时均生存,国际预后指数(international prognostic index,IPI)在本组中未显示预后,多因素分析提示纵隔巨块与预后相关。结论:PMBCL在本组中男性多见,临床表现凶险,须尽快明确诊断。蒽环类为主的化疗联合放疗可取得较好疗效,初治时获得完全缓解尤为关键,伴有巨块者预后差。     

原发纵隔的弥漫大B细胞非霍奇金淋巴瘤34例临床分析

目的:探讨原发纵隔的弥漫大B细胞非霍奇金淋巴瘤(PMLBL)的临床特征及治疗策略.方法:回顾性分析34例原发纵隔的弥漫大B细胞非霍奇金淋巴瘤的临床特点和不同治疗方案对患者生存期的影响.结果:临床分期79.4%为Ⅰ～Ⅱ期,50.0%患者起病时出现上腔静脉压迫综合征,47.1%有邻近器官侵犯.采用化、放疗联合治疗29例(85.3%)、单纯化疗5例(14.7%)、自体造血干细胞移植9例(26.4%).根据寿命表法分析,全组5和10年无瘤生存率(DFS)为47.8%和41.0%,5和10年总生存率(OS)为54.4%和54.4%.自体造血干细胞移植组较常规化、放疗组5年DFS和OS均有所提高,但无显著性差异(P＞0.05).不良预后因素分析显示,具有巨大肿块及治疗后未能获得完全缓解者预后差(P＜0.05).结论:原发纵隔的弥漫大B细胞非霍奇金淋巴瘤具有独特的临床和病理特点,治疗以化、放疗为主.具有不良预后因素的患者可考虑自体外周血造血干细胞移植(APBSCT),但最佳的治疗方案尚需进一步的前瞻性随机研究证实.     

Primary mediastinal B-cell lymphoma

Primary mediastinal B-cell lymphoma (PMBCL) is a sub-type of the heterogeneous diffuse large B-cell lymphoma category, and comprises approximately 5% of all non-Hodgkin's lymphomas (NHL). It was first recognized as a distinct clinico-pathologic entity 20 years ago, and recent work has further characterized specific molecular features. Gene expression profiling has suggested a partial overlap with nodular sclerosing Hodgkin lymphoma (HL), with which it shares some clinical features. The optimal management remains a matter of debate. There is uncertainty as to whether weekly alternating chemotherapy regimens may be more effective than CHOP, whether consolidation radiotherapy (RT) to the mediastinum is always required, whether PET scanning can be used to determine this, and whether the use of rituximab as part of initial therapy will change the answers to these questions. The International Extranodal Lymphoma Study Group (IELSG) 26 clinicopathologic study of PMBCL, which has recently opened, represents a first attempt to gather data prospectively on some of these issues.     

Primary mediastinal large B-cell lymphoma: clinical study of a distinct clinical entity and treatment outcome in 20 patients: review of the literature

Primary mediastinal B-cell lymphoma (PMBCL) is a discrete subset of large B-cell lymphoma with unique clinicopathologic features. The question of optimal treatment emerges because it is an uncommon but not rare occurrence. A retrospective study was therefore conducted in a group of patients in Greece to evaluate the clinical features and treatment outcome in this disease. Twenty patients with PMBCL, with a median age of 42 years, treated at centers participating in the Hellenic Cooperative Oncology Group over the last 20 years, were reviewed. Thirteen (65%) had bulky disease at the time of presentation, 7 (35%) had superior vena cavae obstruction, and 15 (75%) had extranodal involvement. All received doxorubicin-containing chemotherapy, followed in 11 cases by mediastinal radiotherapy. With a median follow-up of 91 months, the median survival is 67.7 months. These data are consistent with those reported from other centers concerning the patient's characteristics, natural history, response pattern to chemoradiation therapy, and prognosis. Response to therapy proved of prognostic significance. A key question that remains is the prompt identification of patients who would benefit from innovative or more intensive therapies.     

Primary Mediastinal Large B-cell Lymphoma

Primary mediastinal B-cell lymphoma (PMBCL) is a relatively rare lymphoma subtype affecting mainly young adults. Its molecular signature and clinical features resemble classical Hodgkin lymphoma. The optimal chemotherapy for this lymphoma subtype has not been established. The addition of rituximab to anthracycline based chemotherapy improved response rates and survival. Many centers use R-CHOP as standard treatment, but the role of the intensified regimens and consolidation radiotherapy has to be clarified. Recent data coming from retrospective analyses and an ongoing prospective study addressing the problem of consolidation radiotherapy will help to better identify risk groups and apply risk-adapted and effective treatment strategies. The latest research has helped to understand molecular mechanisms of PMBCL pathogenesis and indicated targets of directed therapy for the future.     

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Fidelity of Diagnosis Using WHO Criteria

PurposeDiagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity between a working diagnosis of PMBCL at our institution and the clinicopathologic criteria established within the 2017 World Health Organization (WHO) classification.Patients and MethodsMedical records and archived tissue of patients treated for stage I-II PMBCL from 1998 to 2018 were retrospectively reviewed for clinical and pathologic conformity with current WHO criteria. Disease was characterized as definitely PMBCL if all of the following were present: anterior mediastinal mass with or without lymph node involvement, no extranodal disease, B-cell antigen expression, Epstein-Barr virus negativity, and at least one supportive feature: female gender under age 40, bulky primary tumor, CD30 weakly positive, compartmentalizing alveolar fibrosis, lack of surface immunoglobulin expression, and MUM1 or CD23 positivity. Disease without supportive features or other pathologic findings more suggestive of other entities was characterized as equivocal for PMBCL. Lack of an anterior mediastinal mass, presence of distant lymph node involvement or extranodal disease, lack of B-cell antigen expression, or Epstein-Barr virus positivity were characterized as definitely not PMBCL. Clinical management and outcomes were also assessed.ResultsOf 63 patients treated for presumed stage I-II PMBCL, 58 (92%) met the criteria for PMBCL. The most common reason for a discordant diagnosis was lack of an anterior mediastinal mass (n = 3). Two additional patients were characterized as having disease equivocal for PMBCL. In retrospect, one patient most likely had a mediastinal gray zone lymphoma due to CD15 positivity and another diffuse large B cell, not otherwise specified, at pathologic review. Five-year progression-free and overall survival were 67% (95% confidence interval, 54-77) and 81% (95% confidence interval, 68-89), respectively, for all patients.ConclusionDespite the complexity of the clinicopathologic criteria of PMBCL, most patients (92%) who were treated for stage I-II PMBCL at our institution appear to have been accurately diagnosed.