Bronchial infiltration with diffuse large B-cell lymphoma

Non-Hodgkin's lymphoma (NHL) refers to a heterogeneous group of lymphoproliferative diseases with a diversity of clinical courses, including involvement in another organs. NHL frequently involves the thoracic structures, and particularly the mediastinum and lung parenchyma. Several clinical reports have described bronchial-associated lymphoid tissue (BALT) lymphoma as an endobronchial lesion, but endobronchial infiltration with diffuse large B-cell lymphoma is extremely rare. Here, we provide the first report of this condition confirmed by a histopathological study and the presence of an immunoglobulin heavy chain (IgH) gene rearrangement detected by a polymerase chain reaction (PCR).     

弥漫大B细胞淋巴瘤研究最新进展

弥漫大B细胞淋巴瘤(DLBCL)是成年人发生率最高的淋巴瘤亚型,是一组高度异质性的肿瘤,不同亚型有不同的生物学特征、临床表现及治疗反应,患者预后差别很大,尽管目前的标准治疗R-CHOP方案为基础的免疫化疗使DLBCL治愈率提高,但仍有约40％的患者治疗早期即出现耐药或达到缓解后复发,预后差.本文结合第59届美国血液学会(ASH)年会有关报道,对DLBCL的新分子分型、新靶点药物研发、复发难治患者治疗等的研究进展进行总结.     

微小RNA与弥漫大B细胞淋巴瘤

微小RNA（miRNA）是一类小分子非编码RNA,通过与目标mRNA互补序列结合,在转录水平调控基因的表达。研究发现,包括弥漫大B细胞淋巴瘤在内的不同恶性肿瘤中存在特定的miRNA表达谱。因此,体液、组织标本中miRNA的表达将有望成为评估弥漫大B细胞淋巴瘤的新指标。     

Emerging drugs for diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin lymphoma in western countries. Despite the addition of rituximab to chemotherapy, the prognosis is still poor and almost one-third of patients fail or relapse after first-line treatment. Gene expression profiling has identified three main signatures related to subgroups with different biological characteristics and responses to treatment. Novel agents targeting the oncogenic drivers of these subsets are currently under investigation with the aim of providing a tailored approach and avoiding unnecessary toxicity. Herein, we review the emerging therapies for DLBCL with a focus on preclinical and early clinical trials as well as future directions.     

弥漫大B细胞淋巴瘤治疗进展

弥漫大B细胞淋巴瘤(DLBCL)是最常见的恶性淋巴瘤.虽然R-CHOP标准治疗方案改善了DLBCL患者的整体生存,但高危患者5年总生存率仍<50%.因此DLBCL一直是研究和关注的热点,如新药的联合治疗、以嵌合抗原受体T细胞(CAR-T)和抗体治疗为代表的免疫靶向治疗、如何降低治疗的长期不良反应以及寻找新的预后生物学标志物和分型系统等.文章就第60届美国血液学会年会上DLBCL的最新进展进行概述.     

弥漫性大B细胞淋巴瘤临床病理分析

 目的　探讨弥漫性大 B细胞淋巴瘤（DLBCL）的临床病理特征、免疫表型,以提高对DLBCL的诊断水平。方法　对22例DLBCL患者进行回顾性分析,复习组织形态和临床表现,补充完善所有患者CD20、CD3、CD10、bcl-6、MUM-1、Ki-67免疫表型测定,为与其他肿瘤相鉴别,对精原细胞瘤、间变性大细胞性淋巴瘤、母细胞型套细胞淋巴瘤部分病例检测AE1／3、PLAP、CD30、ALK、CD5和CyclinD1。结果　22 例患者均为原发DLBCL,男性14例,女性8例,年龄21～71岁,平均48岁;13例结内,9例结外。生发中心细胞（CGB）型13 例（结内7例,结外6例）,非CGB（non-CGB）型9例（结内6例,结外3例）,结合临床和组织形态学17例可诊断,再结合免疫组织化学22例均可诊断。结论　DLBCL形态学、免疫表型及临床表现有一定的特征性,三者相结合能较准确诊断。     

Prognostic models for diffuse large B-cell lymphoma

Prognosis of DLCL patients is variable and associated with well-defined risk factors. In the past decade several pretreatment variables have been incorporated into prognostic models to predict the death risk of individual patients. The International Prognostic Index (IPI), developed in an international consensus study, has been one of the most widely accepted of these models. In our study we applied some of the major prognostic models proposed for DLCLs in a cohort of 111 patients uniformly treated with a CHOP-like regimen in order to compare their sensitivity and specificity. We also evaluated the possibility of improving the IPI with the inclusion, from among the variables analysed, of serum beta-2 microglobulin level (beta-2M). The sensitivity, reflecting the ability to predict all failures in the cohort of patients as a whole, has improved from 45 to 73 per cent when the beta-2M-IPI model is compared with IPI, without a significant loss of specificity. Based on these results, the beta-2M-IPI may be useful for identifying the subset of patients with very poor prognoses. Therefore, the use of the serum beta-2M value in addition to the IPI may help in selection of the patients with DLCL at higher risk for treatment failure, and identification of those who may require specifically tailored therapeutic approaches.     

Management of relapsed diffuse large B-cell lymphoma

Despite more effective front-line regimens, a substantial portion of patients with diffuse large B-cell lymphoma relapse and require further therapy. Several trials have established the efficacy of autologous stem cell transplantation for relapsed diffuse large B-cell lymphomas, but the benefit has been largely restricted to patients with chemosensitive disease and low-risk features at the time of relapse. In an effort to improve outcomes following an autologous transplant, researchers are exploring several avenues, including improvement of salvage regimens, addition of radioimmunotherapy to preparative regimens, and application of posttransplant treatments to eliminate minimal residual disease. Allogeneic stem cell transplantation also appears promising, but there is much to learn about optimal patient selection and timing. This review outlines the current approach to the management of relapsed diffuse large B-cell lymphoma, with an emphasis on newer peritransplant therapies.     

Conditional survival of patients with diffuse large B-cell lymphoma

BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method was used to estimate conditional survival at 0-5 years after diagnosis. RESULTS: The probability of surviving 5 years increases with each year survived for the first 3 years after diagnosis, after which the increase is minimal. The median survival increases from 38 months for all patients to between 108 and 120 months, conditioned on survival for at least 3-5 years. The prognostic capacity of the IPI and the age-adjusted IPI was high at diagnosis, but the significance gradually declined in the first years after diagnosis. Furthermore, the prognostic impact of the individual clinical variables of the IPI was also significant at diagnosis, but 2 years after diagnosis only age had prognostic impact. Multivariate analysis of patients who survived > or = 3 years identified only age as a prognostic factor. CONCLUSION: For patients with DLBCL who have survived more than 1 year after diagnosis, the conditional survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.     

Venous thromboembolism in patients with diffuse large B-cell lymphoma

We conducted a retrospective record review to determine the frequency of venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL). All records from 1990 to 2001 of patients with the diagnosis of DLBCL at a tertiary care hospital were reviewed. Those with transformation from low-grade lymphoma, central nervous system lymphoma, HIV-related lymphoma or with incomplete records were excluded. All episodes of symptomatic VTE confirmed by imaging studies that were either present at diagnosis or occurred during initial treatment were identified. VTE occurred in 27 of 211 patients (12.8%). Stage I disease was associated with a low risk, whereas a high international prognostic index score increased risk. Of patients with VTE, thrombosis was present at diagnosis in 37% and occurred during the first chemotherapy cycle in 22% and during the first three cycles in 82%. The median survival of patients with VTE was 1.04 years [95% confidence interval (CI) = 0.75 - 1.33] compared to 5.2 years (95% CI 1.8 - 8.6) for those without VTE (P = 0.038). We conclude that VTE is a frequent complication of DLBCL that occurs particularly at diagnosis and during initial therapy, and it is associated with a worse prognosis.     

Treatment of elderly patients with diffuse large B-cell lymphoma

With the implementation of rituximab, tremendous progress has been achieved in the treatment of diffuse large B-cell lymphoma (DLBCL). Nevertheless, the majority of patients with DLBCL are over the age of 65 years and the management of these patients is often suboptimal. Standard chemo-immunotherapy with curative approach should be appropriate for all elderly patients who can tolerate it. Therefore, a careful evaluation of each patient is mandatory prior to treatment allocation. R- CHOP regimen (rituximab, cyclophosphamide doxorubicin, vincristine, prednisolone) remains the standard of care, but special attention has to be paid to rigorous supportive care. Patients not fit enough for R-CHOP are candidates for dose-reduced therapy or other palliative strategies.     

Improving outcomes for patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma in the western world. Until the mid 1990s the incidence of DLBCL increased in both sexes, across racial categories, and across all age groups except the very young, the etiology of most cases remains unknown. DLBCL is associated with an aggressive natural history, but it can be cured with combination chemotherapy regimens like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), which has been the mainstay of therapy for several decades. Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy. Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses, and the addition of the monoclonal antibody, rituximab, to CHOP has markedly improved outcomes. Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease.     

弥漫性大B细胞淋巴瘤的治疗选择

弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphpma,DLBCL）是非霍奇金淋巴瘤中最常见的类型,在分子遗传学、免疫表型等方面具有高度异质性,患者临床预后也截然不同。R-CHOP方案为DLBCL标准治疗方案,如何进一步提高DLBCL疗效是近年来的研究热点。2015年美国临床肿瘤学会（ASCO）提出基于细胞起源分型进行R-CHOP+X方案治疗的策略,但这些方案相继失败。基于更加精准的分层方法,筛选出不同DLBCL亚组并进行针对性治疗,是未来DLBCL治疗的方向。此外,抗体-药物偶联物、双特异性抗体和嵌合抗原受体T细胞（chimeric antigen receptor T-cell,CAR-T）等免疫治疗近年来取得突破性进展,为DLBCL患者带来新的希望。本文针对基于精准分层的DLBCL靶向治疗、免疫治疗的最新进展及遗传学检测方法予以综述。      

BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma

To date, the biological significance of breast cancer resistance protein (BCRP) G34A and C421A polymorphisms is largely unknown. Analysis of these two polymorphisms in 156 diffuse large B-cell lymphoma (DLBCL) patients and 376 control subjects revealed an increased risk of DLBCL associated with variant BCRP 421 genotypes (CA and AA), when compared with the wild-type CC genotype [odds ratio = 1.49, 95% confidence interval (CI) 1.02-2.17, P = 0.042]. Moreover, the increased risk was more evident in younger patients (相似文献   

Rituximab and chemotherapy in diffuse large B-cell lymphoma

Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as ‘younger’ or ‘older’: 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.     

Gene expression profiling of diffuse large B-cell lymphoma

Initial gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) revealed that this single diagnosis actually encompasses two distinct diseases that differ in the expression of hundreds of genes. One subtype, germinal center B-cell-like (GCB) DLBCL, strongly resembles normal germinal center B-cells and has a good prognosis following chemotherapy, whereas activated B-cell-like (ABC) DLBCL resembles mitogenically activated blood B cells and has a poor outcome. An expanded analysis of 274 DLBCL cases confirmed the existence of the GCB and ABC subgroups, but demonstrated that additional subgroups exist. Furthermore, two recurrent oncogenic events in DLBCL, t(14;18) and amplification of the c-rel locus on chromosome 2p, were only observed in GCB DLBCL, whereas constitutive activation of NF-kappaB was seen in ABC DLBCL, showing that the gene expression subgroups represent pathogenetically distinct diseases. Gene expression profiling has also been used to identify individual genes that predict overall survival in DLBCL, the majority coming from gene expression signatures that reflect the cell of origin, proliferation rate, and host immune response to the tumor. A multivariate model including 17 genes representing these biological features divided patients with DLBCL into quartiles with strikingly distinct 5-year survival rates, ranging from 73% to 15%. The use of gene expression profiling should eventually lead to an integration of molecular diagnosis and consequent selection of the most appropriate treatment.