Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era

We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 ( P  = 0.022) or Bcl-6 ( P  = 0.021), or GCB subtype ( P  = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 ( P  = 0.001) or MUM1 ( P  = 0.011), or non-GCB subtype ( P  = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group ( P  = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group ( P  < 0.001) and also in the R-CHOP group ( P  < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated. ( Cancer Sci  2009; 100: 1842–1847)     

神经元特异性烯醇化酶在弥漫大B细胞淋巴瘤缓解患者血清中的表达及其意义

目的 探讨神经元特异性烯醇化酶（NSE）在弥漫大B细胞淋巴瘤（DLBCL）缓解患者中的表达情况及其与预后的关系.方法 采用电化学发光法检测40例初次诊断后经6～8个疗程化疗达到缓解的DLBCL患者及20例对照组血清NSE水平,分析NSE表达与预后的关系.结果 DLBCL缓解患者NSE表达阳性率为50％（20/40）,对照组NSE表达阳性率为10％（2/10）,两组间比较差异有统计学意义（P＜ 0.001）;NSE表达阴性及NSE表达阳性DLBCL缓解患者2年无进展生存（PFS）率分别为20.9％和6.6％,两组间差异有统计学意义（P＜0.01）;NSE为预后不良独立危险因素.结论 NSE是DLBCL缓解患者的独立不良预后指标,对判断缓解DLBCL的预后有重要意义.     

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-celllymphoma (DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen (R-CHOP regimen)significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001),Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and-negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.     

Matched-pair analysis comparing the outcomes of primary breast and nodal diffuse large B-cell lymphoma in patients treated with rituximab plus chemotherapy

Primary breast diffuse large B-cell lymphoma (DLBCL) is an extremely rare presentation of non-Hodgkin's lymphoma that has been associated with poorer clinical outcomes compared with nodal DLBCL in the pre-rituximab era. The aim of this study was to investigate the impact of rituximab on clinical outcomes in patients with primary breast DLBCL. Data from 25 female patients with primary breast DLBCL receiving rituximab plus chemotherapy were matched to 75 female patients (1:3) with nodal DLBCL by following five established prognostic factors (age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase level and B symptoms). Overall survival (OS) was similar between primary breast and nodal DLBCL groups (3-year OS rate, 82.2% vs. 90.7%, respectively; p = 0.345). In the analysis of immunohistochemically defined prognostic subgroups, 19 of 20 available cases in the primary breast DLBCL group displayed a non-germinal center (GC) phenotype. Compared with patterns of recurrence, extranodal progression in the breast or central nervous system (CNS) was significantly higher in the primary breast DLBCL group than in the nodal DLBCL group (p < 0.001). Additionally, the stage-modified International Prognostic Index was the only independent prognostic factor for OS in this population. This suggests that clinical outcomes of primary breast DLBCL might no longer be inferior to those of nodal DLBCL in the rituximab era, which might be associated with the intrinsic biologic characteristics of the non-GC phenotype. However, despite including rituximab, extranodal progression in the breast or CNS was problematic. This study was registered at www.clinicaltrials.gov as no. NCT01266668.     

The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian countries

Patients with the germinal center B-cell-like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL) have a significantly better survival rate than those with non-GCB DLBCL. Several studies have examined the proportions of GCB and non-GCB subtypes in large series of DLBCL patients, but it remains unclear if these proportions are the same in different countries. We performed an immunohistochemical analysis of the numbers of GCB and non-GCB subtypes in a large number of patients with DLBCL in Japan and compared the results with literature data for other countries. We found that 71 of 248 patients (29%) had the GCB phenotype and 177 patients (71%) had the non-GCB subtype of DLBCL among our patient population. Assessment of data collected from other studies showed that 31% of DLBCL patients (102/330) have the GCB subtype in Asian countries, but 50% (206/416) express GCB phenotypes in Western countries; based on these data, the occurrence of the GCB subtype of DLBCL was significantly less in Asian countries (p<0.001). Since patients with the GCB phenotype of DLBCL have better survival, future studies of DLBCL should recognize the difference in the proportions of GCB and non-GCB subtypes of DLBCL between Asian and Western populations.     

Impact of Double Expression of C-MYC/BCL2 Protein and Cell of Origin Subtypes on the Outcome among Patients with Diffuse Large B-Cell Lymphoma: a Single Asian Center Experience

Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein isassociated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome inDLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of originsubtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups underresource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high InternationalPrognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival(OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common innon-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictorof inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCBin Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, theprognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 proteinco-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes andprotein expression among the multiethnic groups.     

R-CHOP和CHOP方案治疗两种亚型弥漫大B细胞淋巴瘤患者的近期疗效

背景与目的：根据肿瘤细胞起源不同,可将弥漫大B细胞淋巴瘤（diffuselarge Bcelllymphoma,DLBCL）分为生发中心来源（germinalcenter Bcell like,GCB）及非生发中心来源（non-GCB）两种亚型。在以CHOP方案为标准的化疗基础上,前者预后优于后者。本研究通过比较R-CHOP（Rituximab联合CHOP）和CHOP方案治疗不同亚型DLBCL患者的近期疗效,寻找初诊DLBCL患者最佳一线治疗方案。方法：将2006年11月至2008年2月中山大学肿瘤防治中心内科收治的83例初治DLBCL患者分为GCB和non-GCB两组。按照修订版淋巴瘤疗效评价标准,比较接受R-CHOP或CHOP方案治疗患者的近期疗效;观察Bcl-2在两种亚型中的表达情况,并分析其与近期疗效的关系。结果：83例DLBCL患者中GCB组35例（42．2％）,non-GCB组48例（57．8％）。GCB组一线化疗近期总缓解率74．3％,non-GCB组60．4％,两组相比差异有显著性（P=0．006）。Bcl-2在GCB和non-GCB两亚组的表达差异没有显著性：Bcl-2阳性患者采用R．CHOP方案治疗的近期缓解率（75．6％）明显高于用CHOP方案治疗者（47．8％）,两组相比差异有显著性（P=0．031）：采用不同方案化疗的Bcl-2阴性患者的近期缓解率则差异无显著性（P〉0．05）。结论：GCB组患者接受标准R—CHOP或CHOP方案治疗近期缓解率高于non-GCB组,提示预后良好。加用Rituximab可提高Bcl-2阳性患者的近期缓解率。     

Prognostic Values of Various Clinical Factors and GeneticSubtypes for Diffuse Large B-cell lymphoma Patients: ARetrospective Analysis of 227 Cases

Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-celllymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectivelyreviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), β2-microglobulin (β2-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predictingthe prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-celllike(GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOPmanagement, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%,P=0.288). Conclusion: Elevated LDH and β2-M levels, positive B symptoms, Ann Arbor stage III/IV, and primarynodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have abetter prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment withthe addition of rituximab can improve the prognosis of patients with DLBCL.     

弥漫大B细胞淋巴瘤免疫亚型与临床特征及疗效的关系

目的探讨弥漫大B细胞淋巴瘤(DLBCL)免疫亚型与一线CHOP化疗方案的疗效关系。方法采用免疫组化链霉素抗生物素蛋白-过氧化物酶连接法(SP)检测60例DLBCL石蜡组织中MUM-1、bcl-6和CD10的表达,确定弥漫大B细胞淋巴瘤免疫亚型。60例患者均采用CHOP或CHOP样方案化疗,观察各组的疗效及不良反应。结果弥漫大B细胞淋巴瘤GCB型和非GCB型各30例,GCB型组患者完全缓解率、稳定率合有效率分别为56.7%、6.7%和93.3%,非GCB型租患者完全缓解率、稳定率及有效率分别为26.7%、13.3%和76.7%,两组患者疗效差异有统计学意义(P<0.05)。GCB型组患者3年生存率明显高于非GCB型组,差异有统计学意义(P<0.05)。两组患者不良反应差异无统计学意义(P>0.05)。结论 DLBCL免疫学亚型与CHOP方案疗效存在一定关系,可以作为预后判断的重要因素。     

乳腺弥漫大B细胞淋巴瘤临床特点及预后分析

目的:探讨乳腺弥漫大B细胞淋巴瘤（DLBCL）患者的临床特征及预后。方法:回顾性分析2014年5月起至2018年12月我院收治的18例乳腺DLBCL患者的临床特点及预后。结果:在18例患者中,17例为女性,中位年龄为57岁,病变主要累及右侧乳腺（11/18,61.1%）。将其分为原发性乳腺DLBCL（PB-DLBCL）和继发性乳腺DLBCL（SB-DLBCL）两大类。11例（57.6%）PB-DLBCL与7例（42.4%）SB-DLBCL相比,其具有Ann Arbor分期多为Ⅰ-Ⅱ期（P＜0.01）、B症状少（P=0.013）、相对更高的白细胞计数（P=0.041）、骨髓未累及（P=0.043）、完全缓解（CR）率高（P=0.049）等特点。生存分析发现PB-DLBCL患者5年总生存期（OS）显著长于SB-DLBCL患者（P=0.013）。本研究以非生发中心B细胞型（non-GCB）居多,生发中心型（GCB）与non-GCB型之间OS无显著差异（P=0.885）。所有获得CR患者的生存期均显著延长（P=0.008）。结论:乳腺DLBCL多见于中年女性,以右侧乳腺肿块为主要临床表现,分子分型多为non-GCB型。与SB-DLBCL患者相比,PB-DLBCL患者具有Ann Arbor分期早、B症状少、相对更高的白细胞计数、骨髓未累及、CR率高等特点,并且生存期显著延长。无论是PB-DLBCL和SB-DLBCL,还是GCB型和non-GCB型,获得CR提示预后良好。     

219例弥漫性大B细胞淋巴瘤免疫表型及遗传学特征分析

  目的  探讨国内弥漫性大B细胞淋巴瘤（DLBCL）免疫表型分型及BCL-2和BCL-6基因异常的分布情况。  方法  应用组织芯片和免疫组织化学法及FISH技术对219例DLBCL的免疫表型及BCL-2和BCL-6基因异常进行检测,根据Hans法进行分型;并收集国内7家相关研究报道,进行综合分析。  结果  本组研究结果:219例DLBCL中,非GCB型（165例,75.3%）显著高于GCB型（54例,24.7%）（P < 0.001）。BCL-2基因异常共49例（25.8%）,其中t （14;18）5例（2.6%）均为GCB型;BCL-2基因扩增44例（23.2%）,GCB型4例（8.5%）,非GCB型40例（28.0%）,有显著性差异（P=0.013）。BCL-6基因重排共42例（22.1%）,GCB型7例（14.9%）,非GCB型35例（24.5%）,差异无统计学意义（P=0.189）。BCL-2基因扩增和BCL-6基因重排呈显著负相关（r=-0.180,P=0.013）。8组综合分析:1 259例中非GCB型（879例,69.8%）明显高于GCB型（380例,30.2%）（P < 0.001）;免疫表型中CD10和MUM1阳性率组间差异较小（P=0.047和P=0.048）,而BCL-6及BCL-2阳性率组间存在明显差异（P < 0.001）。  结论  我国DLBCL患者在主要免疫表型和遗传学特征方面具有独特性,对此值得进行深入研究。      

Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.

PURPOSE: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities. EXPERIMENTAL DESIGN: This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1 expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated. RESULTS: Nuclear MUM-1 expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival. CONCLUSION: The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.     

Serum soluble CD27 level is associated with outcome in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone

Since the introduction of rituximab (R), the prognosis for diffuse large B-cell lymphoma (DLBCL) has markedly improved. We evaluated the prognostic significance of serum soluble CD27 (sCD27) in 143 patients with DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone plus rituximab (R-CHOP). Five-year overall survival rates for patients with sCD27≥213 U/mL or <213 U/mL were 38.7% and 76.8%, respectively (p =0.0005). Multivariate analysis revealed that serum sCD27 was significantly correlated with OS (p =0.047). Immunohistochemical staining for CD27 in lymphoma tissues revealed positive lymphoma cells in 22 cases (18.5%) and positive microenvironment T-cells in 62 cases (52.1%) and was negative in the remaining patients. In these three subgroups, median sCD27 levels were 336 U/mL, 242.6 U/mL and 109.9 U/mL, respectively (p =0.004). Thus, serum sCD27 level is associated with CD27 expression on lymphoma cells, and may be a powerful prognostic factor for DLBCL.     

弥漫大B细胞淋巴瘤中c-myc、Bmi-1、胰岛素样生长因子-Ⅰ及胰岛素样生长因子结合蛋白-3的表达及其意义

目的 检测弥漫大B细胞淋巴瘤(DLBCL)中c-myc、Bmi-1、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)及胰岛素样生长因子结合蛋白-3(IGFBP-3)的表达,分析其与患者临床分期、疗效及预后的关系.方法 选择102例初发DLBCL患者(DLBCL组)及60例同期住院或体检者(对照组),用免疫组织化学方法检测淋巴瘤石蜡样本中c-myc、Bmi-1的表达,应用化学发光免疫分析法检测DLBCL组和对照组血清IGF-Ⅰ、IGFBP-3水平,并分析两组间的表达差异,比较不同分型、临床分期、国际预后指数(IPI)分组及化疗前后DLBCL患者的表达差异.结果 c-myc和Bmi-1在DLBCL组织中阳性表达率分别为71.6％(73/102)及61.8 ％(64/102),非生发中心B细胞(non-GCB)组[c-myc:80.0％(48/60);Bmi-1:71.7％(43/60)]的表达高于生发中心B细胞(GCB)组[c-myc:59.5％(25/42);Bmi-1:50.0％(21/42)](均P＜ 0.01);IPI评分越高,二者的表达均越强;Ⅲ～Ⅳ期组与Ⅰ～Ⅱ期组二者表达差异均无统计学意义(均P＞ 0.01).c-myc或Bmi-1基因异常患者与基因正常患者3年无进展生存(PFS)率及总生存(OS)率差异均有统计学意义(均P＜0.05);两基因同时异常患者的3年PFS率及OS率更低,为独立预后指标.DLBCL组血清IGF-Ⅰ及IGFBP-3水平均低于对照组(均P＜ 0.01);患者化疗前血清IGF-Ⅰ及IGFBP-3水平低于化疗后(均P＜0.01);non-GCB组血清IGF-Ⅰ及IGFBP-3水平与GCB组差异均无统计学意义(均P＞0.01);Ⅳ期DLBCL患者及高危组DLBCL患者血清IGF-Ⅰ及IGFBP-3水平较其他组均降低(均P＜0.01).c-myc或Bmi-1基因异常患者与基因正常患者的血清IGF-Ⅰ及IGFBP-3水平差异均无统计学意义(均P＞ 0.01),两基因同时异常患者的血清IGF-Ⅰ及IGFBP-3水平低于基因正常患者.结论 DLBCL患者c-myc和Bmi-1的表达与其生物学特性有关,对预测预后具有一定的意义;血清IGF-Ⅰ及IGFBP-3水平与患者的临床分期有关,并在一定程度上反映疗效.DLBCL患者的c-myc、Bmi-1表达与血清IGF-Ⅰ及IGFBP-3水平有一定的相关性.     

老年人EB病毒阳性弥漫大B细胞淋巴瘤临床病理学特点及预后分析

目的 探讨老年人EB病毒阳性（EBV＋）弥漫大B细胞淋巴瘤（DLBCL）的临床病理学特点及预后.方法 采用回顾性研究的方法 ,收集24例老年EBV＋DLBCL患者,以同期EBV-非特指型DLBCL患者为对照,分析老年EBV＋ DLBCL患者的临床病理学特点及预后.结果 24例老年EBV＋DLBCL患者肿瘤细胞形态上主要表现为单一性或多形性肿瘤细胞增生;多形性病例中常可见有地图状坏死.细胞起源免疫分型主要为非生发中心亚型,分别占91.3％（Hans分型）和100.0％（Choi分型）.CD30阳性率为55.0％,高于非特指型EBV-DLBCL（P＜ 0.001）.在总体生存时间方面,R-CHOP方案治疗的老年EBV＋DLBCL患者和＞50岁EBV-DLBCL患者的中位生存时间分别为44.2个月和29.2个月,两者差异无统计学意义（P=0.587）.结论 老年人EBV＋DLBCL肿瘤细胞形态上主要表现为单一性或多形性肿瘤性增生;多形性病例中常可见不规则坏死.CD30阳性率较高,并且主要为非生发中心B细胞亚型.R-CHOP方案治疗的老年EBV＋ DLBCL患者的总体生存时间与同年龄段非特指型EBV-DLBCL患者相近.     

Correlation Between Immunophenotype Classification and Clinicopathological Features in Chinese Patients with Primary Gastric Diffuse Large B-Cell Lymphoma

Recent studies have shown that diffuse large B-cell lymphoma (DLBCL) can be classified into germinal center B-cell–like (GCB) and non-GCB phenotypes by immunohistochemical staining. The aim of this study was to investigate the correlation of immunophenotypic classification with clinicopathological features in Chinese patients with primary gastric DLBCL to further our knowledge of this disease. Seventy-three patients with a histopathological diagnosis of primary gastric DLBCL were studied. Immunohistochemistry was carried out using the EnVision method to detect the expression of CD10, Bcl-6, and MUM1. The clinicopathologic features and follow-up data were analyzed using the Kaplan–Meier method, log-rank test, and χ ² test. Expression of CD10 was observed in 21.9 % (16/73) of patients, Bcl-6 in 72.6 % (53/73), and MUM1 in 74.0 % (54/73). According to these data, 32.9 % (24/73) of the cases belonged to GCB subtype and 67.1 % (49/73) belonged to non-GCB subtype. There was a significant difference in tumor size and local lymph node metastasis between the GCB and non-GCB groups (P?<?0.05). Complications in the GCB group (4.2 %) occurred less frequently than those in the non-GCB group (18.4 %); however, this difference was not significant (P?>?0.05). Survival analysis revealed that patients in the GCB group had an increased 5-year survival rate compared to those in the non-GCB group (58.5 % vs 35.7 %, χ ²?=?3.939, P?<?0.05). The 5-year survival rate of patients undergoing R-CHOP chemotherapy was significantly longer than that of patients in the CHOP group (74.7 % vs 37.5 %, χ ²?=?4.185, P?<?0.05). The immunophenotype classification of primary gastric DLBCL, which is closely related to the tumor size and local lymph nodes metastasis, was found to have prognostic significance.     

NanoString荧光条形码技术在弥漫大B细胞淋巴瘤分子分型中的临床应用

目的:探讨NanoString荧光条形码技术在弥漫大B细胞淋巴瘤（DLBCL）分子分型中的临床应用,分析细胞起源亚型与患者预后的相关性。方法:收集2014年1月至2019年12月山西省大同市第三人民医院12例及北京大学医学部8例DLBCL患者的肿瘤组织样本,采用Hans模型分为生发中心B细胞（GCB）型1例和非GCB型19例。在mRNA水平利用NanoString技术平台分析样本中15个Lymph2Cx分子分型相关基因的表达水平差异。通过聚类分析对20例DLBCL患者分型,并分析按此分型组间预后的差别。结果:通过NanoString荧光条形码技术对20例DLBCL患者样本进行检测并进行聚类分析后分型显示,11例为类GCB样型,9例为类活化B细胞（ABC）样型;10例类GCB样型按Hans模型为非GCB型。生存分析显示,类GCB样组总生存优于类ABC样型组（ P=0.019）。 结论:NanoString荧光条形码技术可用于DLBCL的细胞起源分型,该分子分型策略可有效预测患者预后。     

CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

BackgroundSeveral biomarkers indicating poor prognosis have been reassessed in patients receiving rituximab combination chemotherapy for diffuse large B-cell lymphoma (DLBCL). However, few studies have investigated outcome in relation to a combination of these biomarkers. In addition, no large-scale studies have reassessed the outcome of patients with CD5-positive DLBCL treated with rituximab.Patients and methodsWe conducted a retrospective study and investigated the predictive value of three biomarkers—BCL2, germinal center (GC) phenotype and CD5—in 121 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.ResultsCD5-positive patients showed significantly poorer event-free survival (EFS) and overall survival (OS) than CD5-negative patients (2-year EFS, 18% versus 73%, P < 0.001; 2-year OS, 45% versus 91%, P = 0.001). However, no significant difference in outcome according to BCL2 or GC phenotype was observed. Multivariate analysis revealed that CD5 expression was a significant prognostic factor for EFS [hazard ratio 14.2, 95% confidence interval (CI) 4.7–43.2] and OS (hazard ratio 20.3, 95% CI 3.6–114.4).ConclusionsCD5 expression was the only significant prognostic factor among the biomarkers examined in this study. Further studies with larger numbers are warranted to confirm the prognostic significance of CD5 expression for patients with DLBCL receiving rituximab-containing chemotherapy.     

Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma:a report of 76 cases

Pediatric diffuse large B-cell lymphoma （DLBCL） is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell （GCB） classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat- sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47：1. The median age was 12 years （range, 2 to 18 years）, and 47 （61.8%） patients were at least 10 years old. Of the 76 patients, 48 （63.2%） had stage Ill/IV disease, 9 （11.8%） had bone marrow involvement, 1 （1.3%） had central nervous system （CNS） involvement, and 5 （6.6%） had bone involvement. The GCB classification was assessed in 45 patients： 26 （57.8%） were classified as GCB subtype, and 19 （42.2%） were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival （EFS） rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification： 17 （54.8%） were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 （45.2%） were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/ IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.     

Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy

Background: Soluble interleukin-2 receptor (SIL-2R) is knownto be a prognostic parameter in patients with diffuse largeB-cell lymphoma (DLBCL) receiving cyclophosphamide, doxorubicin,vincristine and prednisone (CHOP) therapy. However, its prognosticvalue has not been well known since the introduction of rituximab. Patients and methods: We retrospectively evaluated the prognosticimpact of SIL-2R in 228 DLBCL patients, comparing 141 rituximab-combinedCHOP (RCHOP)-treated patients with 87 CHOP-treated patientsas a historical control. Results: Patients with high serum SIL-2R showed significantlypoorer event-free survival (EFS) and overall survival (OS) thanpatients with low SIL-2R in both the RCHOP group (2-year EFS,66% versus 92%, P < 0.001; OS, 82% versus 95%, P = 0.005)and the CHOP group (2-year EFS, 40% versus 82%; OS, 61% versus90%, both P < 0.001). Multivariate analysis including thefive parameters of International Prognostic Index (IPI) andtwo-categorized IPI revealed that SIL-2R was an independentprognostic factor for EFS and OS in the RCHOP group as wellas in the CHOP group. Conclusions: Our results demonstrate that SIL-2R retains itsprognostic value in the rituximab era. The prognostic valueof SIL-2R in DLBCL patients receiving rituximab-combined chemotherapyshould be reassessed on a larger scale and by long-term follow-up. Key words: diffuse large B-cell lymphoma, rituximab, soluble interleukin-2 receptor Received for publication July 5, 2008. Revision received September 11, 2008. Accepted for publication September 16, 2008.