B-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis of B-cell lymphoma involves a complex interaction between tumor cells and the tumor microenvironment (TME), which is composed of stromal cells and extracellular matrix. Although the roles of the TME have not been fully elucidated, accumulating evidence implies that TME is closely relevant to the origination, invasion and metastasis of B-cell lymphoma. Explorations of the TME provide distinctive insights for cancer therapy. Here, we epitomize the recent advances of TME in B-cell lymphoma and discuss its function in tumor progression and immune escape. In addition, the potential clinical value of targeting TME in B-cell lymphoma is highlighted, which is expected to pave the way for novel therapeutic strategies.
Background This study aimed to evaluate the predictive value of systemic inflammation response index (SIRI) in primary gastrointestinal diffuse large B‐cell lymphoma (PGI‐DLBCL) patients and establish a highly discriminating risk prediction model. Methods This retrospective analysis included 153 PGI‐DCBCL patients diagnosed between 2011 and 2021. These patients were divided into a training set ( n = 102) and a validation set ( n = 51). Univariate and multivariate Cox regression analyses were conducted to examine the significance of variables on overall survival (OS) and progression‐free survival (PFS). An inflammation‐covered score system was established according to the multivariate results. Results The presence of high pretreatment SIRI (≥1.34, p < 0.001) was significantly associated with poorer survival and identified as an independent prognostic factor. Compared with NCCN‐IPI, the prognostic and discriminatory capability of the novel model SIRI‐PI showed a more precise high‐risk assessment with a higher area under the curve (AUC) (0.916 vs 0.835) and C ‐index (0.912 vs 0.836) for OS in the training cohort, and similar results were obtained in the validation cohort. Moreover, SIRI‐PI also showed good discriminative power for efficacy assessment. This new model identified patients at risk of developing severe gastrointestinal complications following chemotherapy. Conclusions The results of this analysis suggested that the pretreatment SIRI may be a potential candidate for identifying patients with a poor prognosis. And we established and validated a better‐performing clinical model, which facilitated the prognostic stratification of PGI‐DLBCL patients and can serve as a reference for clinical decision‐making.
Background: Systemic inflammation response index (SIRI) is a novel inflammatory hallmark that is proposed as an adverse prognosticator in a variety of malignancies. Nevertheless, the correlation between SIRI and primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) remains unknown. Our study aimed to evaluate the prognostic value of SIRI in PGI-DLBCL patients treated with CHOP-based therapies and establishing a highly discriminating risk prediction model compared with the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score. Methods: This retrospective analysis incorporated 102 PGI-DCBCL patients (57 patients with gastric DLBCL and 45 patients with intestinal DLBCL) newly diagnosed between January 2011 and June 2020. The SIRI was calculated by utilizing the peripheral blood neutrophil (N), monocyte (M), and lymphocyte (L) counts collected in the last ≤3 days before the initiation of the immunochemotherapy: SIRI= N × M/L. Pretreatment SIRI cutoff that may distinguish the study population into two gatherings with distinctive overall survival (OS) results which was calculated by the receiver operating characteristic (ROC) curve analysis. The prognostic factors associated with OS, the primary endpoint, were screened by multivariate Cox regression analyses and log-rank test as well as progression-free survival (PFS), the secondary endpoint. Performances of the novel model were compared using the area under the curve (AUC) and C-index in the cohort. Results: Among the 102 patients analyzed, there were 64 (62.7%) males and 38 (37.3%) females. The median follow-up time was 39.5 months (95% CI: 30.7-48.2), ranging from 2 to 102 months. A total of 33 patients (32.4%) presented B symptoms at the initial assessment, 74 (72.5%) of patients revealed stage III or IV disease, and 24 (23.5%) of patients had more than one extranodal involvement. Twenty-seven patients (26.5%) showed ECOG PS>2. The optimal SIRI cutoff was identified as 1.34 value by OS outcome, which divided patients into two groups. There were not significant differences in clinical characteristics between two groups (Table 1). Based on the cut-off value of SIRI, the outcomes of patients were distinct within two groups, which was shown in Figure 1. At a median follow-up of 39.5 (95% CI: 30.7-48.2) months, 86 (84.3%) patients were still alive (98.4% for SIRI <1.34 vs 62.5% for SIRI ≥1.34; p < 0.001). Cox regression analysis found three negative prognostic factors on OS: SIRI≥ 1.34 (P=0.001), B symptom (P=0.001), LDH>ULN (P=0.005). Accordingly, SIRI≥ 1.34 (P=0.002), age>60 (P=0.011) and LDH>ULN (P=0.002) emerged to be the indicators in relation to considerably inferior PFS times. Consequences of the multivariate analyses revealed that the prognostic significance of the SIRI on OS and PFS outcomes was independent of other confounders. SIRI could be used to combine with NCCN-IPI and develop a risk score to improve the NCCN-IPI score and identify PGI-DLBCL patients with poor prognosis. Patients with SIRI≥1.34 were allocated 2 points as a risk factor which was calculated in terms of the β coefficients compared with the effect of LDH level (>ULN) in the multivariate analysis of OS. This established an integrated scoring model with a maximum of 10 points when we combined NCCN-IPI with SIRI. Patients were divided into four risk groups and identified as low-risk group (0−3 points), low-intermediate-risk group (4−5 points), high-intermediate-risk group (6−7 points), and high-risk group (≥8 points). As a result, the prognostic and discriminatory capability of the NCCN-IPI plus SIRI was superior to NCCN-IPI alone (AUC: 0.858 vs. 0.814 and C-index: 0.826 vs. 0.801) based on OS in this patient population (Figure 2). Regarding the PFS, SIRI-PI also surpassed the NCCN-IPI with superior AUC (0.766 vs 0.709) and C-index (0.736 vs. 0.709) in discrimination. Conclusion: The results of this retrospective analysis suggested that the pretreatment SIRI was a potent and independent prognostic indicator that may be a potential candidate for identifying patients with poor prognosis in the future clinical practice of PGI-DLBCL. Keywords: Aggressive lymphoma, Clinically relevant, Systemic inflammation response index Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Objective To study the incidence and risk factors of hyperuricemia in young males who rapid entered into the plateau of 4 500 m. Methods The study contained 390 males aged 18–35 years (21.6 ± 2.5 years), who rapidly entered the plateau with an altitude of 4 500 m. According to their basic level of uric acid (UA), they were divided into two groups, high uric acid (HUA) group and normal uric acid (NUA) group. The characteristics and physiological index, such as the body weight and the height, of them were recorded. For the test of the biochemical indicators, the venous blood samples were collected at the altitude of 4 500 m in the morning. The count of blood cells, blood urea nitrogen (BUN), serum creatinine (SCR), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IDBIL) were compared between the two groups. Results The incidence of hyperuricemia was 65.1% (254/390) at 4 500 m. At the altitude of 4 500 m, the mean hemoglobin concentration (MCHC) of red blood cells in the HUA group was significantly lower than that in the NUA group. Hemoglobin (HGB), mean red blood cell volume (MCV), TBIL, IDBIL, BUN, SCR and LDH in the HUA group were significantly higher than those in the NUA group, though without statistically significant differences in the other variables. Meanwhile, multivariate analysis showed at the altitude of 4 500 m, the risk of HUA increased by 0.982, 1.038 and 1.045 times when MCHC decreased by one unit and TBIL and SCR increased by one unit, respectively. Conclusion The incidence of hyperuricemia was high of 65.1% rush entry into the plateau of young male. Decreased MCHC and elevated TBIL and SCR were independent risk factors for hyperuricemia when rapid enter into 4 500 m.
Background: A growing number of epidemiological evidence supports that the coagulation cascade and tumor-associated inflammatory indicators are related to the recurrence and survival of diffuse large B-cell lymphoma (DLBCL). Plasma fibrinogen and neutrophil-lymphocyte ratio (F-NLR) is a novel hallmark that is proposed as an adverse prognosticator in a variety of malignancies. The purpose of this study was to investigate the prognostic impact of the F-NLR score in DLBCL. Methods: In this retrospective study, 231 patients with DLBCL treated between October 2013 to January 2020 at Shandong Provincial Hospital were included. The critical values of fibrinogen and NLR were determined according to receiver operating characteristic (ROC) curve analysis. The included population was stratified into three groups according to the F-NLR score. The prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were screened by multivariate Cox regression analyses and log-rank test. Results: Within the 231 patients analyzed, 55.4% male and 44.6% female were enrolled in this study. There were 138 (59.7%) patients under 60 years old, with mean age of 55.23±15.02 years old. A total of 184 (79.7%) patients had advanced stage (III or IV) disease, and the great majority of people were defined as non-GCB (64.1%) subtypes and had extranodal involvement (86.6%). The cutoff value was identified as 3.12 for NLR (AUC: 0.628), 4.05 g/L for fibrinogen concentrations (AUC: 0.616), and the AUC value was 0.676 for the F-NLR (Fig 1) by OS outcome. The median follow-up period for all patients was 22 months, ranging from 1 to 90 months. After median follow-up time, 101 (43.7%) patients relapsed or progressed and 77 (34.2%) patients died during or after first-line therapy in total. In the further univariate and multivariate analyses, we demonstrated that F-NLR (HR=1.953, 95%CI=1.404-2.717, P=0.000) was an independent prognostic factor of DLBCL survival. We calculated the β for OS value of NLR and fibrinogen according to Cox regression equation. Since the HR for OS of each marker is approximation, we assigned the same weight to each factor in the prognostic scoring model (F-NLR). The model was simplified to 3 groups with F-NLR score of 0: neither hyperfibrinogenemia nor high NLR (low risk; 39.8% of pts), F-NLR score of 1: one of these hematological abnormalities (intermediate risk; 38.5% of pts), or F-NLR score of 2: both hyperfibrinogenemia and high NLR (high risk; 21.7% of pts). As a result, the PFS and OS were significantly worse in DLBCL pts with an F-NLR score of 2 than those with an F-NLR score of 0-1 (P=0.002 Fig 2A, P=0.000 Fig 2B). Moreover, the F-NLR score is significantly associated with clinical outcomes in elderly pts with advanced stage (III or IV) or extranodal involvement through subgroup analysis. Conclusion: This study validates that the F-NLR score, a new inflammation-based grading system, is a promising clinical predictor for DLBCL especially elderly patients with advanced stage (III or IV) or extranodal involvement. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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