145例弥漫性大B细胞淋巴瘤患者静脉血栓栓塞发生率及危险因素分析

目的 探讨145例弥漫性大B细胞淋巴瘤(DLBCL)患者静脉血栓栓塞(VTE)发生率及危险因素。方法 选取2016年5月-2019年8月收治的DLBCL患者145例,依据深静脉血栓超声诊断结果分为VTE组(22例)和无VTE组(123例)。采用多因素logistic回归分析DLBCL患者发生VTE的危险因素,及两组复发率、无复发生存率、总体生存率差异。结果 静脉置管、34个疗程化疗未完全缓解(non-CR)、D-二聚体≥1.44 μg/ml是VTE的独立危险因素(OR=5.143、9.000、16.514,P<0.05),体能评分(PS评分) ≥2分为保护因素(OR=0.170,P<0.05);两组复发率、无复发生存率、总体生存率比较差异无统计学意义(P>0.05)。结论 静脉置管、34个疗程化疗non-CR、D-二聚体≥1.44 μg/ml均为DLBCL患者发生VTE的独立危险因素,PS评分≥2分为保护因素。     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

弥漫大B细胞淋巴瘤患者血清IL-24及IL-6浓度检测 的临床意义

目的：探讨弥漫大B细胞淋巴瘤（DLBCL）患者外周血清IL-24及IL-6的浓度及其临床意义。方法：收集43例DLBCL患者和33例正常对照人群外周血血清，ELISA法检测IL-24及IL-6的浓度，分析血清IL-24及IL-6浓度与患者临床病理指标之间的关系；并计算患者的国际预后指数（IPI）。结果：与正常对照组[IL-24浓度为（58.32±11.81）μg/mL，IL-6为（24.63±7.73）μg/mL]相比，DLBCL患者血清IL-24浓度[（42.18±8.48）μg/mL]明显降低（P<0.01），而IL-6浓度[（45.29±12.71）μg/mL]明显升高（P<0.01），且二者浓度呈明显负相关（r=-0.414，P<0.05）；同时血清IL-24及IL-6浓度与患者临床分期、肿瘤细胞侵犯骨髓状态及IPI均密切相关（P<0.01），而与患者年龄及性别均无明显相关关系（P>0.05）。发生骨髓转移组患者血清中IL-24较正常对照组和未转移组均明显降低（P<0.01），而IL-6浓度明显升高（P<0.01）；同时随着骨髓转移程度的增加，该趋势更为明显。IPI指数>2的患者，外周血IL-24浓度较IPI指数<2的患者明显降低，而IL-6浓度明显升高（P<0.01）。结论：DLBCL患者血清IL-24浓度较低及IL-6浓度较高可能是患者临床症状较重，预后较差的预测指标。血清IL-24及IL-6浓度测定可作为DLBCL的辅助诊断及监测指标，为临床治疗提供科学依据。     

Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II—Report from the German/Swiss SIOP-LGG 2004 cohort

Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment.     

HIV相关淋巴瘤诊治进展

[摘要]　HIV相关淋巴瘤是常见的HIV相关肿瘤之一，在联合抗反转录病毒治疗（combination antiretroviral therapy, cART）出现之前，其治疗效果极差。在cART时代，HIV相关淋巴瘤的基础及临床研究取得了重大进展，这些为挖掘治疗新靶点提供了依据，使优化HIV相关淋巴瘤的诊治成为可能。本文对近年来HIV相关淋巴瘤的诊断和治疗进展进行综述。