新疆维汉弥漫大B细胞淋巴瘤中Bcl-6 c-myc基因易位的差异性研究

  目的  探讨新疆维吾尔族、汉族弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）患者Bcl-6、c-myc基因易位的差异及其临床意义。   方法  采用荧光免疫原位杂交（FISH）方法,对233例DLBCL活体石蜡切片进行Bcl-6、c-myc基因检测。观察Bcl-6、c-myc基因易位与DLBCL患者临床资料的关系,并对不同民族在不同亚型DLBCL中Bcl-6、c-myc基因易位的情况进行比较。   结果  233例DLBCL中,Bcl-6基因重排51例,占21.89%;c-myc基因重排39例,占16.74%;Bcl-6基因易位的表达与患者年龄、性别、发病部位、临床分期和LDH水平无显著相关（P＞0.05）,而与民族、IPI评分、结外侵犯、B症状、DLBCL不同亚型和近期疗效有相关性（P < 0.05）;c-myc基因易位的表达与患者年龄、性别、发病部位、临床分期、LDH水平和DLBCL不同亚型无明显相关性（P＞0.05）,而与民族、IPI评分、结外侵犯、B症状和近期疗效有相关性（P < 0.05）;维、汉不同民族GCB中Bcl-6、c-myc基因易位比较差异均无统计学意义（P＞0.05）;维、汉不同民族非生发中心活化B细胞（non-GCB）中Bcl-6、c-myc基因易位比较差异有统计学意义（P < 0.05）。   结论  Bcl-6,C-myc基因易位的表达与维、汉不同民族、IPI评分、结外侵犯、B症状和近期疗效有相关性;维、汉民族non-GCB亚组中Bcl-6、c-myc基因易位存在差异。      

弥漫大B细胞淋巴瘤预后相关分子标记物

关于弥漫大B细胞淋巴瘤的预后评估，目前临床上应用较多的是国际预后指数IPI，但它仅是一些临床指标的结合，对相当大的一部分患者的预后不能做出准确评估。一些基因及其表达蛋白在淋巴瘤的发生发展中起着关键的作用。Bel-6、Bcl—2、survivin、p53等分子生物学预后指标对指导DLBCL的预后评估有较高的价值。     

早期韦氏环弥漫大B细胞淋巴瘤预后分析

目的 分析早期韦氏环弥漫大B细胞淋巴瘤(WR-DLBCL)接受CHOP为主治疗的疗效及预后因素。方法 2006-2018年间收治137例确诊为WR-DLBCL患者,其中Ⅰ期22例,Ⅱ期115例。全组接受了CHOP类为主方案化疗,其中62例使用了利妥昔单抗,87例接受了累及野放疗。Kaplan-meier法计算总生存(OS)、无进展生存(PFS)、无局部区域复发生存(LRRFS),并Logrank法检验和单因素分析,Cox模型多因素分析。结果 全组5年OS、PFS、LRRFS分别为78.6%、69.5%、83.2%,综合治疗组分别为87.5%、80.2%、90.9%,单纯化疗组分别为64.2%、53.6%、72.9%。单因素分析显示乳酸脱氢酶、国际预后指数评分、大肿块、利妥昔单抗、化疗周期及综合治疗是影响OS、PFS因素;乳酸脱氢酶、大肿块、综合治疗是影响LRRFS因素。多因素分析显示乳酸脱氢酶、综合治疗模式、利妥昔单抗是影响OS因素,LDH、综合治疗模式是影响PFS因素,LDH是影响LRRFS因素。结论 早期WR-BLBCL预后良好,在利妥昔单抗治疗的时代,化疗联合放疗的综合治疗方式仍然是早期WR-BLBCL的有效手段。     

早期韦氏环弥漫大B细胞淋巴瘤预后分析

目的 分析早期韦氏环弥漫大B细胞淋巴瘤(WR-DLBCL)接受CHOP为主治疗的疗效及预后因素。方法 2006-2018年间收治137例确诊为WR-DLBCL患者,其中Ⅰ期22例,Ⅱ期115例。全组接受了CHOP类为主方案化疗,其中62例使用了利妥昔单抗,87例接受了累及野放疗。Kaplan-meier法计算总生存(OS)、无进展生存(PFS)、无局部区域复发生存(LRRFS),并Logrank法检验和单因素分析,Cox模型多因素分析。结果 全组5年OS、PFS、LRRFS分别为78.6%、69.5%、83.2%,综合治疗组分别为87.5%、80.2%、90.9%,单纯化疗组分别为64.2%、53.6%、72.9%。单因素分析显示乳酸脱氢酶、国际预后指数评分、大肿块、利妥昔单抗、化疗周期及综合治疗是影响OS、PFS因素;乳酸脱氢酶、大肿块、综合治疗是影响LRRFS因素。多因素分析显示乳酸脱氢酶、综合治疗模式、利妥昔单抗是影响OS因素,LDH、综合治疗模式是影响PFS因素,LDH是影响LRRFS因素。结论 早期WR-BLBCL预后良好,在利妥昔单抗治疗的时代,化疗联合放疗的综合治疗方式仍然是早期WR-BLBCL的有效手段。     

原发腹膜弥漫大B细胞淋巴瘤一例

<正>患者男性,55岁,于2013年11月24日因进食后腹部绞痛就诊,无发热、恶心、呕吐、黑便、便血等症状。腹部彩超结果示肝内胆管结石并钙化;下腹肠间隙少量积液。经解痉治疗后疼痛缓解。20 d后再次出现腹部隐痛,剑突下明显,伴腹胀、盗汗,体温仍正常。肠镜、胃镜检查均未见明显异常。体检:ECOG评分为2分;浅表淋巴结无肿大;腹部膨隆,未触及明显肿块,移动性浊音阳性,心肺无明显异常,双下肢不     

弥漫大B细胞淋巴瘤的治疗进展

抗CD20单克隆抗体美罗华的导入,使弥漫大B细胞淋巴瘤的治疗发生了根本性的改变,免疫化疗使这种高度侵袭性的淋巴瘤50%可以达到治愈。然而,对于难治复发的弥漫大B细胞淋巴瘤仍然是棘手的问题。深入的研究发现弥漫大B细胞淋巴瘤是一种高度异质性的肿瘤,基因谱分析至少可以将其分为三种预后不同的类型,生发中心来源的弥漫大B淋巴瘤具有更好的预后,是弥漫大B淋巴瘤的一个独立预后预测因素。分子靶向治疗初见端倪,有免疫修饰调节剂,针对哺乳动物雷帕霉素靶蛋白(mTOR)及其激酶,蛋白酶体,组蛋白乙酰化酶等有关细胞信号传导分子药物问世。尽管有大量的新药出现,单独用于弥漫大B淋巴瘤的治疗效果有限,需要与化疗联合进行更多的临床试验,期待弥漫大B淋巴瘤的疗效有进一步提高。     

弥漫大B细胞淋巴瘤survivin和caspase-3表达的临床意义

目的探讨弥漫大B细胞淋巴瘤survivin、caspase-3表达与临床预后的关系。方法收集1997年至2000年间初治弥漫大B细胞淋巴瘤94例,用免疫组化SP法检测其survivin、caspase-3表达情况。应用SPSS10．0软件进行生存分析,并对各临床指标与预后的关系进行单因素和多因素分析。结果94例弥漫大B细胞淋巴瘤的survivin和caspase-3阳性表达率分别为68．1％和76．6％,其表达与国际预后指数（IPI）显著相关（P〈0．05）。survivin和caspase-3表达阳性患者的复发率高,survivin阳性患者的5年生存率（31．3％）明显低于survivin表达阴性患者（64．0％,P〈0．05）。多因素分析显示,survivin表达是弥漫大B细胞淋巴瘤的独立预后指标。结论survivin和caspase-3可作为弥漫大B细胞淋巴瘤的疗效和预后指标,与IPI结合可在早期筛选出常规治疗预后不良的病例,有助于指导临床治疗,改善预后。     

高危弥漫大B细胞淋巴瘤的诊断和治疗进展

非霍奇金淋巴瘤（Non—Hodgkin’s Lymphoma，NHL）是目前增长速度最快的恶性肿瘤，严重威胁着人类的生命和健康。NHL分为B细胞性、T细胞性和NK细胞性三大类。弥漫大B细胞淋巴瘤（DL-BCL）为其中最常见的淋巴瘤类型，在美国每年约有25000例新发病例，约占全部非霍奇金淋巴瘤的30％-40％；在中国也属最常见的病理亚型，     

Bcl-6与弥漫大B细胞淋巴瘤的相关性研究

弥漫大B细胞淋巴瘤（DLBCL）是最常见的一类非霍奇金淋巴瘤（NHL）,占NHL30％-40％,也是一组异质性疾病,其临床特征、组织学、免疫表型、细胞遗传学和分子遗传学在不同的病例之间会有所差异。尽管联合化疗能使40％-50％的患者达到持续缓解,但仍有许多DLBCL患者不能缓解或缓解后复发。随着对肿瘤发病机制的深入认识,我们逐渐认识到一些基因及其蛋白表达可能在肿瘤的发生发展中起着关键的作用。     

乙型肝炎病毒感染和弥漫大B细胞淋巴瘤相关性研究进展

弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）是临床上较常见的恶性肿瘤,近年来其发病率有明显上升的趋势。乙型肝炎病毒（hepatitis B virus,HBV）感染在世界范围内普遍存在。有研究发现 DLBCL 患者 HBV 感染率较一般人群高,二者存在一定的相关性。     

Prognostic value of MYC rearrangement in cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma

BACKGROUND:

B‐cell lymphoma, Unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience referred to here as unclassifiable B‐cell lymphoma, is a category in the 2008 World Health Organization system used for a group of histologically aggressive neoplasms that are difficult to classify definitively. Currently, there is no established standard therapy for these neoplasms.

METHODS:

The authors assessed MYC status and correlated it with treatment response and outcome in a group of 52 patients with unclassifiable B‐cell lymphoma treated with either a standard DLBCL regimen (R‐CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone‐related therapy]) or more intensive regimens, such as R‐hyper‐CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high‐dose methotrexate and cytarabine). The regimens were selected by the treating clinicians based on the overall clinical and pathological findings.

RESULTS:

Thirty (58%) unclassifiable B‐cell lymphomas had MYC abnormalities (MYC⁺) including 27 with rearrangement, 2 with amplification, and 1 with both. The MYC⁺ and MYC^? groups were similar in their age distribution and International Prognostic Index scores. Progression‐free survival of patients with MYC⁺ unclassifiable B‐cell lymphoma treated initially with R‐CHOP was significantly worse than patients treated with R‐hyper‐CVAD (P = .0358). In contrast, for the MYC^? unclassifiable B‐cell lymphoma group, some patients responded to R‐CHOP, and others were refractory to R‐hyper‐CVAD.

CONCLUSIONS:

MYC aberrations are common in unclassifiable B‐cell lymphoma. The presence of MYC aberrations identifies a patient subset that requires more aggressive therapy than R‐CHOP. In contrast, MYC^? unclassifiable B‐cell lymphoma patients responded variably to either R‐CHOP or aggressive therapy, and the latter showed no survival advantage. Cancer 2011;. © 2011 American Cancer Society.     

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an ‘aggressive B‐cell non‐Hodgkin's lymphoma’, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of ‘B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma’, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.     

17例原发胃肠道弥漫大B细胞淋巴瘤临床病例分析

目的:探讨原发胃肠道弥漫大B细胞淋巴瘤（PGI-DLBCL）的临床特点、治疗方案及疗效。方法:收集我院2006年12月至2013年4月诊治的17例PGI-DLBCL患者的临床资料,对其临床特征、治疗方法、疗效进行回顾性分析,临床分期采用Ann Arbor分期法,采用国际预后指数（IPI）和Ki-67评估,观察短期缓解率,分析临床因素对疗效的影响。结果:17例PGI-DLBCL患者中,男女比例为1.13∶1（男9例,女8例）,中位年龄47岁（15~69岁）;有B症状者6人,占35.3%;随访时间为4~70个月,中位随访时间为12个月;Ann Arbor分期Ⅰ/Ⅱ期10例（58.8%）,Ⅲ/Ⅳ期7例（41.2%）;IPI评分≤2分患者11例（64.7%）,IPI评分＞2分患者6例（35.3%）;6例可评估免疫分型的患者中生发中心型4例（66.7%）,非生发中心型2例（33.3%）;按部位,胃12例,结肠3例,直肠2例;所有患者均接受2疗程以上的化疗,采用CHOP、CHOP（E）方案化疗患者9例（52.9%）,采用利妥西单抗联合化疗者8例（47.1%）。近期疗效显示:16例可评估患者,5例CR（31.3%）,5例PR（31.3%）,3例SD（18.8%）,3例PD（18.8%）;IPI评分≤2分患者50%达CR,IPI评分>2分患者均未达CR;7例Ann Arbor分期Ⅲ-Ⅳ期患者,1例达CR（14.3%）,9例Ann Arbor分期Ⅰ-Ⅱ期患者,4例达CR（44.4%）;7例患者联合了利妥西单抗治疗,总有效率达71.4%（2例CR、3例PR）,9例未联合利妥西单抗治疗,总有效率为55.6%（3例CR、2例PR）。结论:17例PGI-DLBCL患者多为中年,确诊依靠手术或内镜病理活检,大部分患者Ki-67表达＞40%,需加强超声胃镜及PET-CT检查,以便更好的评估预后。预后相关因素分析显示IPI评分与其预后相关。治疗中利妥西单抗联合化疗的治疗反应较好,需扩大样本进一步研究。     

弥漫性大B细胞淋巴瘤诊治进展

弥漫性大B细胞淋巴瘤(DLBCL)是目前最常见的成人非霍奇金淋巴瘤,不同亚型在临床表现、遗传学以及分子生物学等特征方面存在明显差异,所观察到的遗传学改变主要集中在BCL6,BCL2,cMYC,FAS(CD95)的突变和体细胞超突变的异常上。虽然CHOP方案化疗能够治愈部分DLBCL,但完全缓解率仅为45%~55%。强化化疗方案或干细胞移植可改善某些患者的长期生存,最突出和一致改善弥漫性大B细胞淋巴瘤的长期生存效果则是随着抗CD20单克隆抗体药物与化疗的联合应用。     

ALK+弥漫大B细胞淋巴瘤的研究进展

ALK+弥漫大B细胞淋巴瘤(anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma, ALK+DLBCL)是弥漫大B细胞淋巴瘤的一种罕见的亚型, 具有特殊的免疫母细胞或浆母细胞样的形态学特点, 免疫表型独具特征, 细胞遗传学异常, 在儿童和成人都可发生。此病虽然罕见, 但是其临床过程具有侵袭性且预后不良, 因此明确认识该疾病的特点是诊断的关键。ALK+DLBCL对传统化疗方案反应性差, 最近推出的小分子ALK抑制剂可能对这种疾病的患者提供了一个潜在的新的治疗选择。      

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an “aggressive B‐cell non‐Hodgkin's lymphoma”, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of “B‐cell lymphoma, unclassificable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma”, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.     

Reversible posterior leukoencephalopathy syndrome following CHOP chemotherapy for diffuse large B-cell lymphoma

A 63-year-old female with stage IE diffuse large B-cell lymphomadeveloped reversible posterior leukoencephalopathy syndrome (RPLS)following CHOP chemotherapy, with typical clinical and radiologicalfindings. RPLS is a rare neurological syndrome characterised by visualdisturbances, seizures, headaches and altered conscious level which hasbeen associated with malignant hypertension, pre-eclampsia and somedrugs, including ciclosporin. It has not been previously reportedfollowing CHOP chemotherapy. Alternative treatment should be consideredfor patients who develop this rare complication.     

Clinical characteristics and outcome for hepatitis C virus-positive diffuse large B-cell lymphoma

Several previous studies have addressed the association between hepatitis C virus (HCV) infection and non-Hodgkin lymphoma (NHL), but there are few studies on HCV-related diffuse large B-cell lymphoma (DLBL). We conducted this retrospective study to investigate the distinctive clinical characteristics and outcome for HCV-positive DLBL. We compared the clinical characteristics and outcomes of 32 HCV-positive DLBL cases from nine Korean institutions with those of 371 HCV-negative DLBL cases. A higher percentage of HCV-positive DLBL cases were associated with old age (≥60) than HCV-negative DLBL cases at diagnosis (59.4% vs. 36.1%, respectively, P = 0.009) and HCV-positive cases were less likely than HCV-negative cases to have extranodal involvement (53.1% vs. 71.1%, respectively, P = 0.044). The nodal presentation was the only independent factor favorably influencing the event free survival (EFS) in HCV-positive DLBL (HR = 0.11, 95% CI; 0.01 - 0.95, P = 0.012). In comparison to patients with HCV-negative DLBL, HCV-positive DLBL patients had a superior complete response rate (P = 0.023) and EFS (P = 0.02). In Korean patients, HCV-positive DLBL is more common with old age and has less extranodal involvement than does HCV-negative DLBL. The superior survival outcome for HCV-positive DLBL should be verified by further investigation, especially with respect to its correlation with transformed low-grade NHL.     

Ibrutinib抑制弥漫大B细胞淋巴瘤细胞生存的作用研究

  目的  探讨Bruton酪氨酸激酶（Bruton's tyrosine kinase,BTK）抑制剂ibrutinib抑制弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）细胞生存的作用及其相关机制。  方法  用不同浓度的ibrutinib处理DLBCL细胞系SUDHL-10、HBL-1和患者原代细胞,以MTT法检测细胞的增殖抑制情况;以Annexin V/PI流式细胞术和DAPI染色法检测细胞的凋亡情况;应用Western blot法检测细胞表达磷酸化BTK、AKT、ERK的变化。DLBCL细胞与MSC共培养后,体外克隆形成实验和NOD/SCID肿瘤模型小鼠检测ibrutinib在肿瘤微环境里对DLBCL细胞的抑制作用。  结果  2.5μmol/L及更高浓度的ibrutinib对DLBCL细胞的增殖有明显的抑制作用,且呈剂量依赖性。1.0、2.5μmol/L ibrutinib作用于SUDHL-10细胞24 h,细胞凋亡率分别为（21.73±3.64）%和（34.71±2.36）%,高于对照组（3.55±1.89）%（P < 0.05）。5、10μmol/L ibrutinib处理24 h后,DLBCL细胞系均出现核皱缩（5μmol/L）、碎裂（10μmol/L）。ibrutinib处理细胞后磷酸化BTK、AKT、ERK的表达均明显降低。ibrutinib抑制共培养时DLBCL细胞的体外克隆形成（P < 0.01）及DLBCL细胞在体内的增殖生长,差异均具有统计学意义（P < 0.05）。  结论  ibrutinib可抑制细胞系SUDHL-10和HBL-1的增殖,诱导凋亡,其机制可能通过阻断AKT、ERK信号途径而实现;在肿瘤微环境中ibrutinib同样对DLBCL细胞具有较强的抑制生存的作用,该药物有望为DLBCL的治疗带来希望。      

原发性胃弥漫大B细胞淋巴瘤的临床分析

目的 分析原发性胃弥漫大B细胞淋巴瘤(PG-DLBCL)患者的临床特征和预后影响因素,探讨PC-DLBCL的分期系统和治疗模式.方法 回顾性分析69例PG-DLBCL患者的临床资料,以无事件生存期(EFS)和总生存期(OS)为主要研究终点.结果 全组患者的1、3和5年无事件生存率分别为83.8%、71.1%和69.0%,平均EFS为91.3个月;1、3和5年总生存率分别为91.3%、80.3%和72.4%,平均OS为98.8个月.单因素分析结果显示,改良Ann Arbor分期为ⅠE或ⅡE1期、血清乳酸脱氢酶(LDH)水平正常、血红蛋白水平正常、血清白蛋白水平正常、国际预后指数(IPI)评分为0～1分、肿瘤长径＜5 cm、浸润深度浅的患者EFS和OS显著延长(均P＜0.05),而患者的性别、年龄、有无B症状、ECOG体力评分结果以及治疗方法与患者的预后无关(均P＞0.05).Cox多因素回归分析结果显示,改良Ann Arbor分期、血清白蛋白水平是影响PG-DLBCL患者EFS和OS的独立因素.结论 PG-DLBCL的分期系统和各种治疗措施所处的地位仍存有争议,需进一步大样本的前瞻性研究以优化PG-DLBCL的治疗方案.