Association between tumor necrosis factor-α gene polymorphisms and diffuse large B-cell lymphoma in Chinese Han population: evidence from two center case-control study and a meta-analysis

Objectives: The tumor necrosis factor-α (TNF-α) gene, which plays crucial roles in tumorigenesis, is reported to be an independent marker for cancer. This study aims to examine the association between the TNF-α G308A polymorphism and DLBCL risk based on the two center case-control studies and meta-analysis. Methods: In the current study, we performed a two centers case-control study to investigate the effect of the TNF-α G308A polymorphism on DLBCL risk in Chinese Han population. A meta-analysis including 10 published datasets along with current dataset, including 111 comparisons containing 34,041 cases and 42,730 controls were enrolled, was next performed to further confirm the association after literature search was conducted and relevant studies were identified from PubMed, Embase, and Web of Science. Results: The TNF-α -308A allele was associated with a significantly increased DLBCL risk in the two independent patient case-control studies and additionally for pooled analysis from the two sets (P<0.05 for both). The result of meta-analysis further demonstrated that the A allele of -308A was significantly correlated with DLBCL risk under the allelic model (OR=1.35, 95% CI=1.27-1.44) without heterogeneity by fixed-effects model analysis (Q=17.30, P=0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis. Conclusion: This study suggested that -308A polymorphism may be associated with the susceptibility of DLBCL in a Chinese population. The further meta-analysis provides additional evidence supporting the above result that the risk allele of the -308A polymorphism may increase DLBCL risk.     

脂多糖上调人牙髓细胞B细胞淋巴瘤-2蛋白及其相关X蛋白的表达

目的：探讨脂多糖（LPS）作用于人牙髓细胞后,B细胞淋巴瘤-2（Bc1-2）蛋白、Bcl-2相关X蛋白（Bax）在正常人牙髓和炎症牙髓中的表达,探讨其在牙髓炎症过程中的作用机制。方法在体外用不同质量浓度LPS刺激人牙髓细胞后,采用免疫细胞化学染色方法在不同的时间点检测Bcl-2、Bax的表达,用图像分析系统Simple?PCI?version?5.1分析。结果正常人牙髓细胞中Bcl-2、Bax表达量不高,而在牙髓炎症过程中两者均增强,但是随着LPS质量浓度的增加,Bcl-2的表达量开始下降,而Bax的表达则持续增强。结论内毒素能使人牙髓细胞膜上的Bcl-2、Bax表达增强,但Bax的表达强于Bcl-2,内毒素可能通过两者介导的信号传导途径引起细胞凋亡。     

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai,China

Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8–29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.     

Wiskott–Aldrich Syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans

Wiskott–Aldrich Syndrome protein (WASp) regulates the cytoskeleton in hematopoietic cells and mutations in its gene cause the Wiskott–Aldrich Syndrome (WAS), a primary immunodeficiency with microthrombocytopenia, eczema and a higher susceptibility to develop tumors. Autoimmune manifestations, frequently observed in WAS patients, are associated with an increased risk of mortality and still represent an unsolved aspect of the disease. B cells play a crucial role both in immune competence and self-tolerance and defects in their development and function result in immunodeficiency and/or autoimmunity. We performed a phenotypical and molecular analysis of central and peripheral B-cell compartments in WAS pediatric patients. We found a decreased proportion of immature B cells in the bone marrow correlating with an increased presence of transitional B cells in the periphery. These results could be explained by the defective migratory response of WAS B cells to SDF-1α, essential for the retention of immature B cells in the BM. In the periphery, we observed an unusual expansion of CD21^low B-cell population and increased plasma BAFF levels that may contribute to the high susceptibility to develop autoimmune manifestations in WAS patients. WAS memory B cells were characterized by a reduced in vivo proliferation, decreased somatic hypermutation and preferential usage of IGHV4-34, an immunoglobulin gene commonly found in autoreactive B cells.In conclusion, our findings demonstrate that WASp-deficiency perturbs B-cell homeostasis thus adding a new layer of immune dysregulation concurring to the increased susceptibility to develop autoimmunity in WAS patients.     

De-escalating therapy in gastric aggressive lymphoma

The treatment of primary gastric diffuse large B-cell lymphoma (DLBCL) has changed radically over the last 10–15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori (H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy.     

联合利妥昔单抗治疗对高龄DLBCL的疗效及安全性影响

目的 探究联合利妥昔单抗的治疗方案对我国75 岁及以上老年弥漫大B 细胞淋巴瘤（DLBCL）患者的预后是否有改善。方法 回顾性分析2013 年1 月～2019 年5 月我院诊治的69 例75 岁及以上老年DLBCL 患者病例资料,根据治疗方式分为免疫化疗组和对症支持组,比较两组一般资料及总生存,多因素分析影响患者预后的相关因素。免疫化疗组根据2 疗程治疗后疾病是否进展分为未进展组和进展组,比较两组总生存情况。结果 全部患者中位随访时间为447 d,免疫化疗组2 个疗程后13 例患者完全缓解（27.1%）,17 例部分缓解（35.4%）,预计平均生存时间为1925.582 d,对症支持治疗组为122.985 d,差异有统计学意义（P=0.000）。多因素分析发现,仅治疗方式对OS 的影响有统计学意义（P=0.000）,仅对症支持治疗患者的死亡风险是免疫化疗患者的37.473 倍。免疫化疗组未出现治疗相关死亡,其未进展组和进展组3 年生存率比较（87.5% vs 50.0%）,差异有统计学意义（P=0.023）。结论 对于75 岁及以上老年弥漫大B 淋巴瘤患者,与仅对症支持治疗相比,联合利妥昔单抗的治疗可显著提高患者总生存率,且相对安全。对此类患者,治疗上不能一味追求疾病完全缓解,而是维持疾病不要进展对于患者预后有重要意义。     

以全血细胞减少为首发表现的脾边缘区淋巴瘤1例报告

脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)是指原发于脾脏的B淋巴细胞性非霍奇金淋巴瘤。SMZL的发病率低,国内以全血细胞减少为首发表现的SMZL报道较少。为提高临床医务人员对SMZL的认识,现将本院诊治的1例报道如下。1病例资料患者女性,76岁,以“腹胀、纳差1年,全血细胞减少3 d”为主诉于2016年6月23日于本院就诊。1年前曾于本院就诊,患者无明显诱因出现腹胀,伴有纳差,无腹痛、腹泻,无畏寒发热,无瘀斑瘀点,无咳嗽咳痰等不适,建议患者进一步检查明确原因,患者予以拒绝。