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1.
Exp Hematol ; 129: 104125, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38743005

ABSTRACT

The revised International Prognostic Index (R-IPI) is an important prognostic tool in diffuse large B cell lymphoma (DLBCL); however, outcomes can vary markedly within R-IPI groups, and additional prognostic markers are needed. We conducted a prospective observational study to evaluate the circulating immature myeloid (IM) cell subsets and cytokine profiles of 31 patients with newly diagnosed DLBCL before and after chemoimmunotherapy. Among circulating IM cells, myeloid-derived suppressor cells (MDSCs) were the predominant cell type (73.8% ± 26%). At baseline, circulating monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) were predominantly mutually exclusive. Patients with DLBCL clustered into three distinct immunotypes according to MDSC levels and subtype predominance: M-MDSChigh, PMN-MDSChigh, and MDSClow. The M-MDSChigh immunotype was associated with the germinal center B cell-like (GCB) subtype and elevated serum IL-8 and MIP-1α levels. PMN-MDSChigh was associated with the non-GCB subtype and elevated IL-8, MCP-1, IP-10, TNFα, and IL-1Ra levels. Standard chemoimmunotherapy partially reduced M-MDSC distribution across the MDSClow and M-MDSChigh groups. By contrast, among the MDSClow and PMN-MDSChigh groups, PMN-MDSCs persisted after treatment. Two high-risk patients with non-GCB DLBCL and MDSClow immunotype experienced early disease recurrence within 12 months of treatment completion. This study demonstrates that distinct types of MDSCs are associated with subtypes of DLBCL. MDSC levels are dynamic and may be associated with disease status. Persistence of PMN-MDSCs among high-risk patients with DLBCL may be associated with early relapse.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Myeloid-Derived Suppressor Cells , Humans , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/pathology , Myeloid-Derived Suppressor Cells/metabolism , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/blood , Female , Male , Middle Aged , Aged , Prognosis , Inflammation/pathology , Adult , Prospective Studies , Aged, 80 and over , Cytokines/blood , Immunotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
3.
Clin Exp Med ; 24(1): 105, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771501

ABSTRACT

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker. After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3+ cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance. Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R2 = 0.76, p = 0.02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3.46, P = 0.03). Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.


Subject(s)
Erythrocyte Indices , Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Humans , Male , Female , Middle Aged , Immunotherapy, Adoptive/methods , Adult , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/blood , Aged , Prognosis , Treatment Outcome , Biomarkers/blood , Receptors, Chimeric Antigen , Cohort Studies , Young Adult , Leukapheresis
4.
Open Vet J ; 14(4): 980-989, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38808287

ABSTRACT

Background: Canine lymphoma is the most common hematopoietic cancer in dogs. Numerous studies have evaluated the prognostic value of hematological abnormalities and ratios in both humans and dogs with lymphoma. Aim: To compare hematological parameters and complete blood count ratios between a population of dogs affected by lymphoma and healthy dogs to identify potential prognostic markers for lymphoma. Methods: This retrospective case-control study compares hematological parameters and complete blood count ratios between a population of 114 dogs affected by multicentric large B-cell lymphoma (LBCL) and 60 healthy dogs. Results: The study found several statistically significant differences between the hematological indices of LBCL dogs and healthy dogs, but no correlation between these parameters and the survival times of 78 dogs treated with chemotherapy Madison Wisconsin protocol. In addition, hematological alterations were evaluated such as anemia, leukocytosis, and thrombocytopenia. Conclusion: Hematological ratios have been suggested as potential prognostic markers for canine LBCL but their real prognostic value remains controversial and requires future investigation.


Subject(s)
Dog Diseases , Dogs , Animals , Dog Diseases/blood , Dog Diseases/diagnosis , Retrospective Studies , Case-Control Studies , Male , Female , Blood Cell Count/veterinary , Lymphoma, Large B-Cell, Diffuse/veterinary , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, B-Cell/veterinary , Lymphoma, B-Cell/blood , Lymphoma, B-Cell/diagnosis , Prognosis
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 458-465, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660852

ABSTRACT

OBJECTIVE: To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. RESULTS: Patients were divided into low B-cell count group (B cell<0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated ß2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). CONCLUSION: Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.


Subject(s)
B-Lymphocytes , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/diagnosis , Prognosis , Retrospective Studies , Lymphocyte Count , Male , Female , Middle Aged
6.
Curr Treat Options Oncol ; 25(5): 659-678, 2024 05.
Article in English | MEDLINE | ID: mdl-38656685

ABSTRACT

OPINION STATEMENT: Diffuse large B-cell lymphoma (DLBCL) is a curable disease with variable outcomes due to underlying heterogeneous clinical and molecular features-features that are insufficiently characterized with our current tools. Due to these limitations, treatment largely remains a "one-size-fits-all" approach. Circulating tumor DNA (ctDNA) is a novel biomarker in cancers that is increasingly utilized for risk stratification and response assessment. ctDNA is readily detectable from the plasma of patients with DLBCL but has not yet been incorporated into clinical care to guide treatment. Here, we describe how ctDNA sequencing represents a promising technology in development to personalize the care of patients with DLBCL. We will review the different types of ctDNA assays being studied and the rapidly growing body of evidence supporting the utility of ctDNA in different treatment settings in DLBCL. Risk stratification by estimation of tumor burden and liquid genotyping, molecular response assessment during treatment, and monitoring for measurable residual disease (MRD) to identify therapy resistance and predict clinical relapse are all potential applications of ctDNA. It is time for clinical trials in DLBCL to utilize ctDNA as an integral biomarker for patient selection, response-adapted designs, and surrogate endpoints. As more ctDNA assays become commercially available for routine use, clinicians should consider liquid biopsy when treatment response is equivocal on imaging. Incorporating MRD may also guide decision-making if patients experience severe treatment toxicities. Though important barriers remain, we believe that ctDNA will soon be ready to transition from bench to bedside to individualize treatment for our patients with DLBCL.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/genetics , Humans , Circulating Tumor DNA/blood , Biomarkers, Tumor/blood , Liquid Biopsy/methods , Disease Management , Translational Research, Biomedical , Precision Medicine/methods , Prognosis , Clinical Decision-Making , Disease Susceptibility
7.
Int J Hematol ; 119(6): 697-706, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38492199

ABSTRACT

We conducted a multi-institutional retrospective study in 100 transplant-ineligible (TI) patients with diffuse large B-cell lymphoma (DLBCL) that relapsed or progressed after first-line R-CHOP (or -like) therapy to develop a robust predictive model for TI relapsed/refractory (r/r) DLBCL, which has a heterogeneous but poor prognosis by currently available treatment modalities other than chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies. The median age at relapse or progression was 76 years. The median progression-free survival (PFS) and overall survival (OS) from the first progression were 11.5 months and 21.9 months, respectively. Multivariate analysis identified low lymphocyte-to-monocyte ratio (LMR), elevated high lactate dehydrogenase, and elevated C-reactive protein at progression as independent predictors of OS. A predictive model based on these three factors, here designated as the Kyoto Prognostic Index for r/r DLBCL (KPI-R), successfully stratified their OS and PFS with statistical significance. In addition, event-free survival less than 24 months for R-CHOP and low LMR were identified as significant predictive factors for non-response in any sequence of salvage therapy. We concluded that LMR is a bonafide predictor of treatment response and prognosis in patients with TI r/r DLBCL, and may be helpful in treatment decision-making.


Subject(s)
Lymphocytes , Lymphoma, Large B-Cell, Diffuse , Monocytes , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Aged , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Aged, 80 and over , Lymphocytes/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Rituximab/administration & dosage , Rituximab/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Recurrence , Prednisone/administration & dosage , Prednisone/therapeutic use , Adult , Vincristine/administration & dosage , Vincristine/therapeutic use
8.
Leuk Lymphoma ; 65(5): 618-628, 2024 May.
Article in English | MEDLINE | ID: mdl-38337191

ABSTRACT

Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median (p = .003) and non-germinal center B-cell-like (non-GCB) DLBCL (p = .049) had worse progression-free survival than patients with a tumor burden less than the median or GCB DLBCL. Multi-factor assessment combining orthogonal features from a single pretreatment plasma sample has promise as a prognostic indicator in this setting (p = .085). This minimally invasive plasma-based NGS assay could enable comprehensive prognostic assessment of patients in a clinical setting, with greater accessibility than current methods.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , High-Throughput Nucleotide Sequencing , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/diagnosis , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Biomarkers, Tumor/blood , Prognosis , Male , Female , Middle Aged , Aged , Tumor Burden , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mutation , Aged, 80 and over
9.
Oncologist ; 29(5): e672-e680, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38297976

ABSTRACT

BACKGROUND: Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression. METHODS: Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the "dominant circulating clonotype," whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the "dominant tissue-matched clonotype." The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of "dominant tissue-matched clonotype" proportion or "dominant circulating clonotype" proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and ß2-microglobulin. RESULTS: A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of "dominant circulating clonotype" and "dominant tissue-matched clonotype" was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and "dominant circulating clonotype" proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the "dominant tissue-matched clonotype" and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64). CONCLUSION: IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.


Subject(s)
Circulating Tumor DNA , Disease Progression , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Female , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Middle Aged , Aged , Adult , Prognosis , Aged, 80 and over , Immunoglobulin Heavy Chains/genetics , Gene Rearrangement
10.
Int J Lab Hematol ; 45(5): 735-742, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37350020

ABSTRACT

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in the western world. It is highly heterogeneous with a variable clinical course, but curable with chemo-immunotherapy in up to 70% of all cases. The lymphoma presents in lymph nodes and/or extranodal lymphoid tissue, and the diagnosis is based on invasive procedures for histopathologic evaluation. METHODS: In this technical study, we evaluated cell-free DNA (cfDNA) from blood plasma to detect clonal B cells in patients with DLBCL using rearranged immunoglobulin heavy chain gene as targets by next-generation sequencing. Clonal B cell sequences and frequencies were determined from blood plasma cfDNA and cellular DNA from matched excised lymphoma tissues and mononuclear cells isolated from diagnostic bone marrow and blood samples from 15 patients. RESULTS: We showed that identical clonal rearrangements could be detected in blood plasma and excised lymphoma tissue and that plasma cfDNA was superior in detecting clonal rearrangements compared to blood or bone marrow-derived cellular DNA. CONCLUSION: These findings consolidate the role of blood plasma as a reliable and easily accessible source for detecting neoplastic cells in DLBCL.


Subject(s)
B-Lymphocytes , Cell-Free Nucleic Acids , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Humans , Cell-Free Nucleic Acids/blood , B-Lymphocytes/pathology , High-Throughput Nucleotide Sequencing , Genes, Immunoglobulin Heavy Chain
12.
Br J Haematol ; 196(3): 617-628, 2022 02.
Article in English | MEDLINE | ID: mdl-34664256

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogenous malignancy, early identification of patients for relapse remains challenging. The potential to non-invasively monitor tumour evolutionary dynamics of DLBCL needs to be further established. In the present study, 17 tumour biopsy and 38 plasma samples from 38 patients with high-intermediate/high-risk DLBCL were evaluated at baseline. Longitudinal blood samples were also collected during therapy. Circulating tumour DNA (ctDNA) was analysed using targeted sequencing based on a gene panel via a recently developed methodology, circulating single-molecule amplification and re-sequencing technology (cSMART). We found that the most frequently mutated genes were tumour protein p53 (TP53; 42·1%), histone-lysine N-methyltransferase 2D (KMT2D; 28·9%), caspase recruitment domain family member 11 (CARD11; 21·1%), cAMP response element-binding protein binding protein (CREBBP; 15·8%), ß2 -microglobulin (B2M; 15·8%), and tumour necrosis factor alpha-induced protein 3 (TNFAIP3; 15·8%). The mutation profiles between ctDNA and matched tumour tissue showed good concordance; however, more mutation sites were detected in ctDNA samples. Either TP53 or B2M mutations before treatment predicted poor prognosis. Analysis of dynamic blood samples confirmed the utility of ctDNA for the real-time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Female , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Humans , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Mutation , Neoplasm Grading , Neoplasm Staging , Prognosis , Prospective Studies , Treatment Outcome , Tumor Suppressor Protein p53/genetics , beta 2-Microglobulin/genetics
14.
Cell Mol Biol (Noisy-le-grand) ; 67(3): 61-68, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34933732

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and rapid-growing form of non-Hodgkin lymphoma (NHL). The objective of this research was to assess the predictive role of lymphocyte to monocyte ratio (LMR), red cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) values in the survival of DLBCL patients. A retrospective analysis of 136 DLBCL patients admitted to Nanakali Hospital for blood diseases and oncology from 2010-2020 was done. We assessed the correlation of LMR, RDW and NLR with patients' characteristics and the impact on survival by the Kaplan-Meier method, the log-rank test, and Cox regression models for multivariate analysis. The complete remission rate was 61.7%, with a 5- year overall survival (OS) and progression-free survival (PFS) of 59.5% and 60%, respectively. The Log-rank test showed that LMR was significantly correlated with Ann Arbor staging (p= 0.040). There is a significant association between RDW and Eastern Cooperative Oncology Group performance status (ECOG-performance status) (p= 0.022), B symptoms (p= 0.026), Revised International prognostic index (R-IPI) (p= 0.004), lactate dehydrogenase (LDH) (p= 0.021), and beta 2 microglobulin (B2MG) (p= 0.007), whereas NLR had a significant correlation with LDH only (p=0.016). There were no significant differences in the 5-year OS or PFS in patients with different levels of RDW, LMR, and NLR. LMR, RDW and NLR were correlated with many of patients' characteristics. However, none of the LMR, RDW and NLR did possess value to predict OS and PFS, and they cannot be used as biomarkers for survival evaluation of DLBCL.


Subject(s)
Erythrocyte Indices , Lymphocytes/pathology , Lymphoma, Large B-Cell, Diffuse/blood , Monocytes/pathology , Neutrophils/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Kaplan-Meier Estimate , Leukocyte Count , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Young Adult
15.
Ann Palliat Med ; 10(10): 10938-10945, 2021 10.
Article in English | MEDLINE | ID: mdl-34763456

ABSTRACT

BACKGROUND: To analyze the relationship between the peripheral blood absolute lymphocyte count (ALC)/absolute monocyte count (AMC) ratio, soluble interleukin 2 receptor (sIL-2R) level, serum programmed cell death 1 (PD-1) level, and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 78 patients with DLBCL admitted to hospital and 30 healthy controls were enrolled as the case group and control group between August 2019 and June 2020, respectively. The ALC/AMC ratio and the levels of sIL-2R and serum PD-1 between the 2 groups and among patients with different prognoses were compared. The evaluation efficiency of these 3 factors for the prognosis of DLBCL patients was analyzed by receiver operating characteristic (ROC) curves. The risk factors affecting the 1-year survival rate were analyzed by the Cox hazard model. RESULTS: The levels of sIL-2R, AMC, and PD-1 in the case group were significantly higher than those in the control group, while the ALC/AMC ratio was lower than that in the control group (P<0.05). The levels of sIL-2R and PD-1 in the poor prognosis group were significantly higher than those in the good prognosis group, while the ALC/AMC ratio was lower than that in the good prognosis group (P<0.05). The areas under the ROC curve (AUCs) of sIL-2R level, serum PD-1 level, and the ALC/AMC ratio in evaluating the prognosis of DLBCL patients were 0.805 (95% CI: 0.700-0.886), 0.825 (95% CI: 0.722-0.902), 0.792 (95% CI: 0.685-0.876), respectively. The critical values were 474.80 µg/L, 206.85 pg/mL and 3.01, respectively. The differences in the 1-year survival rate among DLBCL patients with different tumor sizes, B symptoms, sIL-2R levels, and ALC/AMC ratios were statistically significant (P<0.05). B symptoms (RR =1.721) and ALC/AMC ratio lower than 3.01 (RR =1.484) were independent influencing factors of the 1-year survival rate in DLBCL patients (P<0.05). CONCLUSIONS: The ALC/AMC ratio, sIL-2R level, and serum PD-1 level can effectively assess the prognosis of DLBCL patients. B symptoms and ALC/AMC ratio lower than 3.01 are risk factors affecting the 1-year survival rate of patients.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/diagnosis , Monocytes , Programmed Cell Death 1 Receptor/blood , Receptors, Interleukin-2/blood , Humans , Lymphocyte Count , Lymphocytes , Lymphoma, Large B-Cell, Diffuse/blood , Prognosis , Retrospective Studies
16.
South Med J ; 114(11): 708-713, 2021 11.
Article in English | MEDLINE | ID: mdl-34729615

ABSTRACT

Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmass-forming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.


Subject(s)
Arthroplasty/statistics & numerical data , Fibrin/analysis , Lymphoma, Large B-Cell, Diffuse/complications , Aged , Arthroplasty/methods , Female , Humans , Knee Joint/pathology , Knee Joint/physiopathology , Lymphoma, Large B-Cell, Diffuse/blood , Male , Middle Aged
17.
BMC Cancer ; 21(1): 1255, 2021 Nov 21.
Article in English | MEDLINE | ID: mdl-34802440

ABSTRACT

BACKGROUND: Fatty acid metabolism is reportedly associated with various cancers. However, the role of pretreatment serum free fatty acid (FFA) levels in diffuse large B-cell lymphoma (DLBCL) prognosis is still unclear, and our study aimed to better elucidate its influence on clinical outcomes. METHODS: The medical records of 221 newly diagnosed DLBCL patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2016 were analysed retrospectively. Receiver operating characteristic curve analysis was used to determine a cut-off value for pretreatment serum FFA levels for prognostic prediction in DLBCL patients. The relationship between pretreatment serum FFA levels and clinical and laboratory parameters was analysed. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Newly diagnosed DLBCL patients with high pretreatment serum FFA levels (≥0.495 mmol/l) had more B symptoms, higher serum lactate dehydrogenase levels (> upper limit of normal), >1 extranodal site, and higher International Prognostic Index score (3-5) compared to those with low pretreatment serum FFA levels (<0.495 mmol/l). Higher serum FFA levels were independent prognostic factors for poor OS, but not PFS. CONCLUSIONS: High pretreatment serum FFA levels are associated with lower survival in untreated DLBCL patients.


Subject(s)
Fatty Acids, Nonesterified/blood , Lymphoma, Large B-Cell, Diffuse/blood , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Antineoplastic Agents, Immunological/therapeutic use , Female , Humans , L-Lactate Dehydrogenase/blood , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prognosis , Progression-Free Survival , ROC Curve , Retrospective Studies , Rituximab/therapeutic use , Young Adult
18.
Front Immunol ; 12: 745320, 2021.
Article in English | MEDLINE | ID: mdl-34712233

ABSTRACT

Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3ζ/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1-2 CRS at a median of 4 (range 3-7) days. There were no cases of grade ≥3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-γ, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Cytokine Release Syndrome/prevention & control , Immunotherapy, Adoptive/adverse effects , Lymphoma, Non-Hodgkin/therapy , Neurotoxicity Syndromes/prevention & control , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , C-Reactive Protein/analysis , Cytokine Release Syndrome/blood , Cytokines/blood , Drug Administration Schedule , Female , Ferritins/blood , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Non-Hodgkin/blood , Male , Middle Aged , Neurotoxicity Syndromes/etiology , Premedication , Progression-Free Survival , Receptors, Interleukin-6/antagonists & inhibitors , Salvage Therapy , Severity of Illness Index , Treatment Outcome
19.
J Cancer Res Ther ; 17(4): 951-955, 2021.
Article in English | MEDLINE | ID: mdl-34528547

ABSTRACT

BACKGROUNDS: Non-Hodgkin's lymphoma and Hodgkin's lymphomas (HL) are lymphoid neoplasms. Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are viruses that could proliferate in lymphoid tissues. These viruses may cause lymphoproliferative diseases. The aim of this study was to evaluate the seroprevalence of HBV, HCV, and HIV in patients with diffuse large B-cell lymphoma (DLBCL) and HL, to compare the relationship between these two disease groups and to determine the relationship between the three viruses and their characteristics. MATERIALS AND METHODS: The study was a retrospective study. Patients who were followed up in hematology and hepatitis outpatient units between January 01, 2012, and May 01, 2019, were included in the study. RESULTS: A statistically significant relationship was observed between the disease groups in terms of hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) IgG antibody, hepatitis B e antigen (HBeAg), and anti-HBe seropositivities (P = 0.004, P = 0.006, P = 0.041, and P = 0.014, respectively). There was also a statistically significant relationship between the disease groups in terms of anti-HCV seropositivity (P = 0.029). HBsAg, anti-HBc IgG, HBeAg, anti-Hbe, and HCV seropositivity rates were higher in patients with DLBCL than in patients with HL. CONCLUSION: These findings suggest that there may be a relationship between hepatitis viruses and DLBCL. Evaluation of HBV and HCV infections in these patients before starting treatment is thought to be beneficial in initiating antiviral prophylaxis to prevent reactivation in seropositive cases. In addition, care should be taken for the development of lymphoma in the follow-up of HCV and HBV infections.


Subject(s)
Antibodies, Viral/blood , HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Hodgkin Disease/epidemiology , Lymphoma, Large B-Cell, Diffuse/epidemiology , Adult , Antibodies, Viral/immunology , Antigens, Viral/immunology , Female , Follow-Up Studies , HIV/immunology , HIV Infections/blood , HIV Infections/virology , Hepacivirus/immunology , Hepatitis B/blood , Hepatitis B/virology , Hepatitis B virus/immunology , Hepatitis C/blood , Hepatitis C/virology , Hodgkin Disease/blood , Hodgkin Disease/immunology , Hodgkin Disease/virology , Humans , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/virology , Male , Middle Aged , Prognosis , Retrospective Studies , Seroepidemiologic Studies , Turkey/epidemiology
20.
Future Oncol ; 17(32): 4299-4306, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34350771

ABSTRACT

Aim: To identify risk factors and establish a concise prognostic scoring system in patients with diffuse large B-cell lymphoma (DLBCL). Methods: A total of 131 DLBCL patients were enrolled with long-term follow-up who were treated in Shengjing Hospital of the China Medical University. The relationship between clinical parameters and outcomes was analyzed. Results: Multivariate analysis showed that patient age, BMI, CA125 and rituximab application were independent risk factors. Thereafter, a concise scoring system was established, and the new system could identify high-risk patients (p < 0.0001). The patients were divided into three groups: low-risk, medium-risk and high-risk groups. There were significant differences among different groups on overall survival and progression-free survival by log-rank test (p < 0.05). Conclusion: Old age, low BMI, high CA125 and no rituximab application were independent risk factors for DLBCL. The new established prognostic score system, which includes all the risk factors, could identify high-risk patients.


Lay abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma. Different clinical performance and treatment options lead to different outcomes. Identifying factors that indicate poor prognosis is helpful for clinicians to plan a suitable treatment regimen. Therefore, it is important to establish a concise prognostic scoring system to identify high-risk DLBCL patients. This retrospective study analyzed 131 DLBCL patients with long-term follow-up with R-CHOP or E-CHOP therapy regimen. The result showed that patients' age, BMI, CA125 and chemotherapy regimens with or without rituximab were independent risk factors. Thereafter, we established a concise scoring system, which scored each risk factor including old age, low BMI, high CA125 and no rituximab application as 1 point each. Definition of low-risk (0­1 point), medium-risk (2 points) and high-risk (3­4 points) groups indicated significant differences in prognosis.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/mortality , Adult , Aged , CA-125 Antigen/blood , Female , Follow-Up Studies , Humans , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Membrane Proteins/blood , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Rituximab/therapeutic use
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