Risk stratification model based on VEGF and International Prognostic Index accurately identifies low-risk diffuse large B-cell lymphoma patients in the rituximab era

Sang, Wei; Zhou, Hang; Qin, Yuanyuan; Shen, Ziyuan; Yan, Dongmei; Sun, Cai; Song, Xuguang; Ma, Ying; Tu, Dongyun; Bian, Zhenzhen; Nie, Shanlin; Jin, Yingliang; Xu, Linyan; Li, Zhenyu; Xu, Kailin

doi:10.1007/s12185-021-03145-3

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Patients in HIR/HR groups of IPI had poor survival, which was consistent with one of our previous studies. 31 DLBCL is highly heterogeneous in pathological features and elements of heterogeneity are associated with the prognosis of patients. Therefore, we evaluated the values of PNI on different groups of cell-of-origin, Ann Arbor Stage, ECOG, IPI and other pathological factors.…”

Section: Discussionmentioning

confidence: 99%

The Value of Prognostic Nutritional Index (PNI) on Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: A Multicenter Retrospective Study of HHLWG Based on Propensity Score Matched Analysis

Shen¹,

Wang²,

He³

et al. 2021

JIR

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Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM). Methods: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival. Results:The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cutoff point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan-Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (<2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis. Discussion: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.

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Section: Discussionmentioning

confidence: 99%

The Value of Prognostic Nutritional Index (PNI) on Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: A Multicenter Retrospective Study of HHLWG Based on Propensity Score Matched Analysis

Shen¹,

Wang²,

He³

et al. 2021

JIR

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“…Despite the well-established role of MYC in angiogenesis, 7 and in DLBCL pathogenesis, 3 examination of this relationship has been limited to reports of a positive correlation between MYC expression and serum levels of VEGF, 42,43 without direct vessel quantification in the lymphoma biopsy. We showed that MYC-positive DLBCL biopsies displayed significantly higher MVD and VEGF levels than MYC-negative lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Cyclic‐AMP signalling, MYC and hypoxia‐inducible factor 1α intersect to regulate angiogenesis in B‐cell lymphoma

et al. 2022

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Summary Angiogenesis and MYC expression associate with poor outcome in diffuse large B‐cell lymphoma (DLBCL). MYC promotes neo‐vasculature development but whether its deregulation in DLBCL contributes to angiogenesis is unclear. Examination of this relationship may uncover novel pathogenic regulatory circuitry as well as anti‐angiogenic strategies in DLBCL. Here, we show that MYC expression positively correlates with vascular endothelial growth factor (VEGF) expression and angiogenesis in primary DLBCL biopsies, independently of dual expressor status or cell‐of‐origin classification. We found that MYC promotes VEGFA expression, a correlation that was validated in large datasets of mature B‐cell tumours. Using DLBCL cell lines and patient‐derived xenograft models, we identified the second messenger cyclic‐AMP (cAMP) as a potent suppressor of MYC expression, VEGFA secretion and angiogenesis in DLBCL in normoxia. In hypoxia, cAMP switched targets and suppressed hypoxia‐inducible factor 1α, a master regulator of VEGFA/angiogenesis in low oxygen environments. Lastly, we used the phosphodiesterase 4b (Pde4b) knockout mouse to demonstrate that the cAMP/PDE4 axis exercises additional anti‐angiogenesis by directly targeting the lymphoma microenvironment. In conclusion, MYC could play a direct role in DLBCL angiogenesis, and modulation of cAMP levels, which can be achieved with clinical grade PDE4 inhibitors, has cell and non‐cell autonomous anti‐angiogenic activity in DLBCL.

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“… 15 Sang et al analyzed the specimens of 65 DLBCL patients and found that patients with elevated VEGF had a higher probability of extranodal involvement, high IPI, Myc/Bcl-2 double expression and high Ki-67. 16 In addition, they created a V–IPI model based on VEGF and IPI. Patients were divided into low-risk, low-intermediate-risk, high-intermediate-risk and high-risk groups according to this model, the cumulative progress-free survival (PFS) of four groups were 94.4%, 74.1%, 40.6% and 14.8% ( P < 0.05), the cumulative OS were 100%, 100%, 42.4% and 0% ( P < 0.05), respectively.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

“…Patients were divided into low-risk, low-intermediate-risk, high-intermediate-risk and high-risk groups according to this model, the cumulative progress-free survival (PFS) of four groups were 94.4%, 74.1%, 40.6% and 14.8% ( P < 0.05), the cumulative OS were 100%, 100%, 42.4% and 0% ( P < 0.05), respectively. 16 Drugs with anti-VEGF activity may be promising in the treatment of DLBCL after further exploration. Bevacizumab, an anti-VEGF monoclonal antibody, shows definite effect in several solid tumors, such as non-squamous non-small cell lung cancer 17 and metastatic colorectal cancer.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

Drug-Resistance Mechanism and New Targeted Drugs and Treatments of Relapse and Refractory DLBCL

Zhang¹,

Gu²,

Chen³

2023

CMAR

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Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin’s lymphoma (NHL). 30 ~ 40% of DLBCL patients were resistant to the standard R-CHOP regimen or recurrence after remission. It is currently believed that drug resistance is the main cause of the recurrence and refractory of DLBCL (R/R DLBCL). With the increased understanding of DLBCL biology, tumor microenvironment and epigenetics, some new therapies and drugs like molecular and signal pathway target therapy, chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, antibody drug-conjugate and tafasitamab have been used for R/R DLBCL. This article will review the drug resistance mechanism and novel targeted drugs and therapies of DLBCL.

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Risk stratification model based on VEGF and International Prognostic Index accurately identifies low-risk diffuse large B-cell lymphoma patients in the rituximab era

Cited by 7 publications

References 31 publications

The Value of Prognostic Nutritional Index (PNI) on Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: A Multicenter Retrospective Study of HHLWG Based on Propensity Score Matched Analysis

The Value of Prognostic Nutritional Index (PNI) on Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: A Multicenter Retrospective Study of HHLWG Based on Propensity Score Matched Analysis

Cyclic‐AMP signalling, MYC and hypoxia‐inducible factor 1α intersect to regulate angiogenesis in B‐cell lymphoma

Drug-Resistance Mechanism and New Targeted Drugs and Treatments of Relapse and Refractory DLBCL

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