B细胞淋巴瘤IgH基因重排的检测及临床应用

目的建立克隆性免疫球蛋白重链(IgH)基因重排检测技术,探讨B淋巴细胞IgH基因重排在恶性淋巴瘤诊断的临床价值。方法选取62例B细胞性非霍奇金淋巴瘤(B-NHL),其中,弥漫大B淋巴瘤(DL-BCL)42例、滤泡性B细胞淋巴瘤(FL)15例、套细胞淋巴瘤(MCL)5例;15例未定性的淋巴组织增生性病变;20例良性淋巴组织反应性增生病例。从组织蜡块切片提取基因组DNA,经PCR扩增,聚丙烯酰胺凝胶电泳后银染显示基因重排结果。结果62例B-NHL中53例IgH基因重排(85.5%),其中DLBCL37例、FL13例、MC14例,阳性率分别为88.1%、86.7%、80.0%,各组间阳性率差异无统计学意义(P>0.05);15例未确诊的疑难病例中10例IgH基因重排,其中7例经随访或会诊确认为B-NHL;20例良性淋巴组织反应性增生病例IgH基因重排均为阴性,IgH基因重排检出率在淋巴瘤组与良性组之间差异有统计学意义(P<0.001)。结论PCR法检测B淋巴细胞IgH基因重排可作为淋巴细胞来源的良、恶性病变的一种辅助诊断手段,适用于石蜡标本,进行回顾性研究。     

弥漫性大B细胞淋巴瘤克隆性基因重排检测研究

目的对弥漫性大B细胞淋巴瘤(DLBCL)进行IgH基因重排研究。方法用免疫组化法标记筛选DLBCL,用针对IgH单轮扩增引物对DLBCL石蜡包埋组织进行多聚酶链反应(PCR)扩增检测克隆性基因重排。结果60例DLBCL IgH基因重排阳性率为51.7%(31/60),其中中心母细胞型阳性率54.5%(30/55),免疫母细胞型阳性率0.0%(0/3),间变性大细胞型阳性率50.0%(1/2)。结论DLBCL IgH基因重排检出率低于B细胞淋巴瘤总检出率,可能与DLBCL中存在IgH可变区体细胞超突变及背景细胞的数量有关。     

石蜡切片荧光原位杂交检测弥漫性大B细胞淋巴瘤BCL6基因异常

目的 建立石蜡包埋的淋巴瘤组织切片荧光原位杂交(FISH)技术平台,探讨其在弥漫性大B细胞淋巴瘤(DLBCL)诊断中的价值.方法 应用家用高压锅和水浴变性法在淋巴瘤石蜡切片上行FISH分析,BCL6双色断裂点分离探针FISH检测58例石蜡包埋DLBCL病例中BCL6基因易位和扩增.结果 通过优化实验条件,成功地建立了淋...     

新型病毒TTV传播规律及相关性分析

目的：探讨输血后新型病毒（TTV）传播规律及相关的研究，为预防和阻断TTV的传播提供依据。方法：采用套式PCR检测孕产妇静脉血、脐血和婴儿足跟血以及乳汁的TTV DNA，并对其阳性妇女所生的婴儿随访1年，以进行相关性调查分析。结果：102例孕产妇静脉血TTV DNA阳性检出率为53．9％（55／102）；106例脐血TTV DNA阳性检出率为17．0％（18106）；52例婴儿（均为TTV DNA阳性妇女所生）1周内足跟血阳性检出率为15．4％（8／52）；55例TTV DNA阳性妇女的乳汁，有40例TTV DNA阳性检出率为72．7％（40／55）；对55例TTV DNA阳性妇女所生的57例婴儿，出生后随访1年，除2例外有55名婴儿呈阳性结果。结论：TTV母婴传播率很高，可达96．5，且宫内感染率达15．4％。故认为应尽早制订相应的预防和阻断措施，有效控制宫内感染和监测阳性妇女乳汁中TTV DNA的含量，以降低婴儿感染率。     

Aggressive large B-cell lymphoma in a systemic lupus erythematosus patient with chronic active Epstein-Barr virus infection: a case report

A link between Epstein-Barr Virus (EBV) infection, systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL) has been recently reported in literature. Here we report a case of diffuse large B-cell lymphoma (DLBCL) with a particularly aggressive clinical course in an SLE patient with EBV infection. A 49-year-old woman with a long history of SLE was admitted to the Department of Experimental and Clinical Medicine and dramatically died a few hours later. The autopsy described no evidence of active lymphoproliferative disorder. Instead, histological examination demonstrated an atypical lymphocitic proliferation in lymph node, kidneys, pericardium and uterus. Immunoistochemically, the lymphomatous cells were positive with CD19, CD20, CD22 and CD79a, which was consistent with a DLBCL. The cells were also reactive to EBV markers, indicating the possible role of previous EBV infection in DLBCL pathogenesis.     

Assessment of Correlation Between Early and Late Efficacy Endpoints to Identify Potential Surrogacy Relationships in Non-Hodgkin Lymphoma: a Literature-Based Meta-analysis of 108 Phase II and Phase III Studies

Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II–III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson’s coefficient of determination (R ²). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R ²?=?0.81, 95% confidence interval [CI] 0.51–0.96). Six-month PFS was strongly correlated with 3-year PFS (R ²?=?0.89, 95% CI 0.62–0.96) in FL and was moderately correlated with 2-year OS (R ²?=?0.69, 95% CI 0.40–0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13%?±?1.2% increase in 2-year OS in DLBCL, a 23%?±?1.1% increase in 3-year PFS in FL, or a 6.7%?±?1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R ²?=?0.66 (95% CI 0.52–0.98) and R ²?=?0.69 (95% CI 0.22–0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.     

API2-MALT1融合基因表达与结外弥漫大B细胞淋巴瘤临床病理特征与预后的关系

目的检测结外弥漫大B细胞淋巴瘤AP12-MALTl融合基因mRNA表达,了解其表达与结外弥漫大B细胞淋巴瘤临床病理特征与预后的关系。方法收集胃肠和甲状腺结外弥漫大B细胞淋巴瘤共32例,通过RT-PCR检测所有病例的AP12-MALTl mRNA,收集临床病理资料和随访。根据融合基因表达情况将病例分为两组,即AP12-MALT1mRNA表达与未表达组,比较两组的临床病理特征和预后。结果32例中11例检出融合基因表达(34．4％)。与AP12-MALT1mRNA未表达病例相比较,AP12-MALT1mRNA表达病例临床病理分期较早,细胞增殖指数、淋巴结累及远处转移率和复发率都较低,两组间差异有显著意义。生存分析：AP12-MALT1mRNA表达病例平均存活时间长、5年生存率高,两组的存活情况差异有显著意义。结论AP12-MALT1融合基因表达对结外DLBCL的临床病理特征和预后有明显影响,来源于MALT淋巴瘤恶性转化的DLBCL有具有更加惰性的临床过程和较好的存活情况。MALT淋巴瘤和由它高恶性转化而来的结外DLBCL应被视为同一个临床病理学实体,这样更能体现MALT淋巴瘤的演进过程。     

原发扁桃体非霍奇金淋巴瘤21例临床分析

目的 探讨原发扁桃体非霍奇金淋巴瘤（NHL）的临床病理特征、诊断治疗及预后。方法 回顾性分析天 津医科大学总医院2007年1月—2014年1月收治的经病理确诊的21例原发扁桃体NHL的临床资料,总结其临床病 理特点、分期及预后。结果 21例原发扁桃体NHL占同期行扁桃体手术病理患者的2.6%（21/807）。其中男13例, 女8例,平均发病年龄（50.8±12.9）岁。单侧发病19例（90.5%）。病理学诊断源于B细胞20例（95.2%）,其中弥漫大B 细胞型13例（61.9%）,滤泡性4例（19.0%）,套细胞型3例（14.3%）;源于T细胞1例（4.8%）。按照Ann-Arbor标准分期 Ⅰ~Ⅱ期18例,5年生存率为71.4%;Ⅲ~Ⅳ期3例,5年生存率为0。结论 原发扁桃体NHL较为罕见,早期患者预后 较好,重视本病的早期诊断、早期治疗是提高5年生存率的关键。     

基础研究弥漫性大B细胞淋巴瘤免疫球蛋白基因重排特点及规律研究

目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)生发中心B细胞型(GCB)及非生发中心B细胞型(non-GCB)中Ig基因重排的特点及规律.方法 采用免疫组化法检测46例DLBCL中CD10、BCL-6、MUM1表达,采用Hans免疫分型方法将DLBCL分为GCB和non-GCB;同时提取所有样本基因组DNA,利用BIOMED-2克隆分析系统进行PCR扩增Ig基因,核酸分子异源双链凝胶电泳分析基因重排情况,并以15例反应性增生病变作为阴性对照.结果 46例DLBCL样本中GCB 12例、non-GCB 34例,其中45例样本扩增出Ig基因的克隆性重排条带,检测敏感性为97.8%,15例反应性增生病变均未检测到重排条带,检测特异性为100.0%.GCB和non-GCB重链IGH重排差异无统计学意义(P>0.05),但轻链IGκ-A、IGκ-B和IGλ重排差异有统计学意义(P<0.05).结论 GCB和non-GCB的Ig基因轻链重排条带分布具有显著的特点和规律,可为病理诊断和临床应用提供更为准确的依据.     

Lenalidomide for the treatment of B-cell lymphoma

Introduction: Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Lenalidomide represents an attractive therapeutic option due to its original mechanism of action.

Areas covered: In this review, the authors describe the pharmacological properties of lenalidomide, and the rational for its use in B-cell lymphomas; focusing on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). They discuss the mechanism of action of the drug and its current and future clinical development. They also review the current data in relapsed/refractory situations as well as in first-line treatment.

Expert opinion: Lenalidomide is an oral non-chemotherapy immunomodulatory agent with an acceptable toxicity profile and manageable side-effects. Efficacy has widely been demonstrated, especially in MCL, FL and non-Germinal Center DLBCL patients. Further studies are now warranted to better define the strategy for the use of lenalidomide in B-NHL patients, and clarify which subgroup of patients will really benefit of lenalidomide as part of first-line treatment or in a relapsed/refractory setting.     

Enzastaurin hydrochloride for lymphoma: reassessing the results of clinical trials in light of recent advances in the biology of B-cell malignancies

Introduction: The B-cell receptor (BCR) is critical for the development and persistence of B-cell non-Hodgkin lymphoma (B-NHL). Protein kinase C-beta (PKC-?) has been identified as one of the key signaling hubs downstream of the BCR and constitutes a valuable target in B-NHL. As a potent PKC-? inhibitor, enzastaurin is currently being tested in Phase II/III trials. Areas covered: This review summarizes the latest results and ongoing clinical trials with enzastaurin in light of basic scientific advances in the understanding of various lymphoid cancers, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) and Waldenstr?m's macroglobulinemia (WM). Expert opinion: While its continued clinical development is uncertain, enzastaurin should be regarded as a stepping stone for the development of future therapies; indeed, the recent research has provided valuable insight into the possible molecular mechanisms that explain its limited clinical activity especially in the treatment of DLBCL and MCL. It should be noted that there is still some interest in enzastaurin, in combination, for the treatment of WM.     

PTEN和LIVIN在弥漫大B细胞淋巴瘤组织中的表达及临床意义

目的:探讨PTEN和LIVIN蛋白在弥漫大B细胞淋巴瘤组织中的表达及其临床意义。方法:选取本院2008年7月至2011年5月初治的弥漫大B细胞淋巴瘤组织标本41例,反应性淋巴结增生21例作为对照组,采用免疫组化S-P法检测PTEN和LIVIN的表达,并探讨PTEN和LIVIN的表达与弥漫大B细胞淋巴瘤的分期及预后的关系。结果:PTEN在弥漫大B细胞淋巴瘤组织中表达率为39.00%,对照组表达率为80.95%(P<0.05);LIVIN在弥漫大B细胞淋巴瘤组织中表达率为65.90%,对照组表达率为23.81%(P<0.05)。弥漫大B细胞淋巴瘤组织切片PTEN与LIVIN表达存在显著的负相关。PTEN与患者性别、年龄、行为评分、Ann Arbor-Colswolds分期、结外受累、乳酸脱氢酶(LDH)高低、临床B组症状、IPI及病理类型无关。LIVIN表达与患者性别、年龄、Ann Arbor-Colswolds分期及是否有结外受累无关;与行为评分分组、LDH高低、临床是否伴有B组症状、IPI及病理类型有关。结论:PTEN在弥漫大B细胞淋巴瘤中低表达,与弥漫大B细胞淋巴瘤预后无相关性。LIVIN在弥漫大B细胞淋巴瘤中高表达,与患者行为评分分组、LDH高低、临床是否伴有B组症状、IPI及病理类型有关。LIVIN可作为判断弥漫大B细胞淋巴瘤预后的生物学指标。     

弥漫大B细胞淋巴瘤骨髓侵犯形态学及免疫表型特点分析

目的 探讨弥漫大B细胞淋巴瘤（DLBCL）骨髓侵犯形态学及免疫表型特点,为临床DLBCL侵犯骨髓的准确诊断提供一定的科学依据。方法 收集2014年6月—2019年6月我院收治的59例DLBCL患者的骨髓组织和外周血,分析DLBCL患者的骨髓细胞形态学、骨髓病理学、流式细胞学、荧光原位免疫杂交及其他相关检测的结果与临床特征。结果 59例发生骨髓侵犯的DLBCL患者多数表现为白细胞增高、贫血、血小板减少,有43例（72.88%）外周血中可见数量不等的瘤细胞。59例患者骨髓涂片中瘤细胞占有核细胞比例≥10％的有31例（52.54%）。瘤细胞侵犯骨髓方式以弥漫性增生为主,造血组织明显减少或缺乏。免疫组化染色及流式细胞学检查示,淋巴瘤细胞 CD20、CD19、CD79b及 cCD79a均呈阳性表达,部分患者表达 HLA-DR、CD22、sIgM、CD43、CD10、FMC7及 CD123,均不表达CD38、TdT、CD103、CD25、CD3、CD2、MPO、CD33、CD13、CD7及CD56。12例患者进行FISH检测均未见C-myc基因重排。结论 骨髓形态学、病理学并结合免疫表型检测是DLBCL患者准确诊断的重要依据。     

病毒性肝炎TTV DNA阳性者的临床分型和肝组织学观察

目的：了解输血传播病毒（TTV）感染的临床特点和肝组织形态学特征,探讨TTV与肝损伤的关联性,方法：对93例血清TTV DNA阳性病毒性肝炎患者的临床资料及其中10例单一TTV笔DNA阳性慢性非甲－瘐型肝炎（HNA－G）的肝组织光镜和电镜检查结果进行分析,结果：各型病毒性肝炎中的均有一定比例的TTVDNA阳性,以慢性肝炎,慢性重型肝炎,肝硬化多见,可呈T TV＋HAV,TTV＋HBV,TTV＋HEV,TTV＋HAV,TTV＋HBV＋HCV,TTV＋HBV＋HEV,TTV＋HBV＋HGV重叠感染,与HBV重叠感染可有慢性重型肝炎,肝硬化之临床类型,半日一TTV DNA阳性慢性肝炎患者存在肝细胞变性,坏死和肝组织淋巴细胞浸润,纤维明显增生,结论：TTV DNA阳性慢性肝炎患者在肝细胞变性,坏死和肝组织淋巴细胞浸润,纤维明显增生,结论：TTV在肝脏慢性损伤中可能起一定作用,可引起慢性肝炎并与肝硬化和慢性重型肝炎的发生相关联。     

TD 方案治疗多发性骨髓瘤临床分析

目的：探讨沙利度胺联合地塞米松方案（TD方案）治疗多发性骨髓瘤（MM）的临床疗效及不良反应。方法35例MM患者随机分为TD方案组（A组）15例, VAD方案组（B组）10例,TVAD方案组（C组）10例。沙利度胺起始剂量100 mg/d ,d 1～d 28,地塞米松40 mg/d静脉滴注,d 1～d4;长春新碱0．5 mg/d静脉滴注,d 1～d 4,阿霉素10 mg/d静脉滴注d 1～d 4,28 d 1疗程,连续3个疗程后评价疗效及不良反应。结果部分缓解率A组、B组、C组分别为46．7％、50．0％、50．0％;总有效率分别为80．0％、80．0％、90．0％,差异无统计学意义（P值均大于0.05）。3组不良反应发生率：骨髓抑制分别为20．0％、40．0％、40．0％;心脏损害分别为0．0％、20．0％、20．0％;周围神经病变分别为20．0％、40．0％、50．0％;感染分别为6．67％、30．0％、30．0％,差异均有显著性（ P值均小于0．05）。结论 TD方案治疗MM有较高的缓解率且不良反应发生率最小。     

T细胞淋巴瘤与EB病毒关系的研究

收集贵州地区１００例Ｔ细胞淋巴瘤进行了ＥＢ病毒检测，用免疫组织化学方法确定肿瘤细胞的Ｔ细胞表型；用聚合酶链检测ＥＢ病毒特征的ＤＮＡ序列（ＥＢＶ－ＤＮＡ），用原位杂交法检测ＥＢ病毒编码的ＲＮＡ（ＥＢＥＲ１／２），研究结果表明，贵州地区Ｔ细胞淋巴瘤与ＥＢ病毒关系极为密切，ＥＢ病毒在鼻咽部Ｔ细胞淋巴瘤中起着一定的作用，淋巴母细胞性性Ｔ细胞淋巴瘤与ＥＢ病毒有一定的关系。     

弥漫性大B细胞淋巴瘤IL-6和VEGF表达水平与化疗耐药的相关性

目的探讨弥漫性大B细胞淋巴瘤(DLBCL)患者血清白细胞介素6(IL-6)、血管内皮生长因子(VEGF)的表达及与化疗耐药之间的相关性。方法采用酶联免疫吸附试验(ELISA)分别测定16例化疗耐药患者(化疗耐药组)、20例化疗敏感患者(化疗敏感组)治疗前后和15例健康者(对照组)血清IL-6、VEGF水平。结果化疗耐药组患者血清IL-6、VEGF初治前表达水平明显高于化疗敏感组患者初治前和对照组(P<0.05),治疗缓解后明显低于治疗前(P<0.05)。DLBCL复发耐药时,患者血清中的IL-6、VEGF又高于缓解时水平(P<0.05)。化疗耐药组Ⅲ～Ⅳ期患者治疗前、复发耐药时IL-6、VEGF水平明显高于Ⅰ～Ⅱ期患者(P<0.05)。结论 DLBCL患者血清IL-6、VEGF表达水平的变化,提示其可以作为观察DLBCL病情变化的检测指标,可能与DLBCL细胞耐药有关。     

输血传播病毒感染状况调查

目的　调查河南省不同人群输血传播病毒(TTV)的感染状况。方法　采用酶联免疫法 (ELISA)和套式聚合酶链反应(PCR)法对 321例正常人群、正常献血员、急性肝炎、慢性肝炎和肝癌患者血清进行了抗 -TTVIgG和TTVDNA检测。结果　以上人群TTV感染率分别为 5. 0%、0、11. 25%、17. 24%、26. 42%、34. 18%;混合感染中TTV合并HBV、HCV感染率最高,分别为 32. 20%和 30. 51%。结论　河南省不同人群均有TTV的感染;TTV与各型肝炎均有混合感染;ELISA法检测抗-TTVIgG与PCR法检测TTVDNA结果有较好的一致性。     

Enzastaurin hydrochloride for lymphoma: reassessing the results of clinical trials in light of recent advances in the biology of B-cell malignancies

Introduction: The B-cell receptor (BCR) is critical for the development and persistence of B-cell non-Hodgkin lymphoma (B-NHL). Protein kinase C-beta (PKC-β) has been identified as one of the key signaling hubs downstream of the BCR and constitutes a valuable target in B-NHL. As a potent PKC-β inhibitor, enzastaurin is currently being tested in Phase II/III trials.

Areas covered: This review summarizes the latest results and ongoing clinical trials with enzastaurin in light of basic scientific advances in the understanding of various lymphoid cancers, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) and Waldenström's macroglobulinemia (WM).

Expert opinion: While its continued clinical development is uncertain, enzastaurin should be regarded as a stepping stone for the development of future therapies; indeed, the recent research has provided valuable insight into the possible molecular mechanisms that explain its limited clinical activity especially in the treatment of DLBCL and MCL. It should be noted that there is still some interest in enzastaurin, in combination, for the treatment of WM.     

肝硬化合并以上消化道大出血为首发症状的胃弥漫大B细胞淋巴瘤一例

弥漫大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤（NHL）中发病率最高的一类弥漫生长的B细胞淋巴瘤。该病以进行性淋巴结肿大为最主要的临床表现,可结外发病,临床表现多样性,易被误诊。本文报告为以上消化道出血为首发症状,合并肝硬化,内镜表现为胃溃疡的胃DLBCL患者1例。期望通过对本病例分析以提高对DLBCL的认识和诊治水平。