Project description:Few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and particular, plasma cell neoplasia. This ongoing single-center study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma and related plasma cell dyscrasia, after the first dose of anti-SARS-CoV-2 vaccination. The 82 patients included in this study received SARS-CoV-2 vaccines (including mRNA- and vector-based vaccines) as a routine measure. After the first vaccination, a positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts. A cut-off value of ≥30 CD19+ B cells/µL was significantly positive correlating with higher SARS-CoV-2 SP-AbT. In contrast, current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease significantly correlated negatively with SARS-CoV-2 SP-AbT. Conversely, treatment with immunomodulatory drugs did not harm the development of antibody titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination.
Project description:Background Up to now, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma (MM) and related plasma cell dyscrasias, after the first dose of anti-SARS-CoV-2 vaccination. Methods In this single-center study, patients aged 18 years and older with a confirmed diagnosis of MM, monoclonal gammopathies of clinical significance (MGCS) or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations were included. Data were collected between January 1st and May 21th, 2021, at the department of oncology and hematology at the University Medical Center Hamburg-Eppendorf, Germany. The primary aim of this study was to evaluate a possible correlation between antibody titers and CD19+ B lymphocyte count and secondary to identify other possible factors influencing immune response. This study is part of the COVIDOUT trial (NCT04779346). Written informed consent was provided by each patient according to local requirements. Results A total of 82 patients were included in this study. The median age was 67.5 years (range 40-85 years). 78 patients had MM, 2 MGCS, and 2 AL. Overall, 63 patients were vaccinated with mRNA-based and 19 with vector-based vaccines, respectively. At the time of vaccination, 69 (84.1%) patients were under current anti-myeloma treatment. In total, 34 (41%) patients received anti-CD38-targeting therapies and 52 (63%) patients received IMiD-based therapies. 57 (69.5%) patients were in deep remissions (very good partial remission or better) at the time of vaccination. Assessment of anti-SARS-CoV-2 spike protein antibody titer (SP-AbT) took place on a median of 25 days after the first vaccination (SD ± 11.8). A positive SP-AbT was detected in 23% (17/74) of assessable patients. A cut-off value of ≥ 30 CD19+ B cells/µl was significantly positively correlating with higher SARS-CoV-2 SP-AbT. Individuals with current anti-CD38-antibody treatment showed lower SP-AbT and the likelihood for positive titer results was significantly lower in patients with current anti-CD38 treatment compared to those without. Treatment with immunomodulatory drugs did not harm the development of antibody titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease (≤ partial remission) were significantly negatively correlated with SARS-CoV-2 SP-AbT. Conclusion Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.
Project description:ObjectivesPatients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations.MethodsPatients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC). Anti-SARS-CoV-2 spike glycoprotein antibodies were measured at 4-8 weeks following the second COVID-19 vaccine dose (either BNT162b2 or ChAdOx1 nCoV-19) using a CE-marked combined ELISA detecting IgG, IgA and IgM (IgGAM). Antibody levels were considered as a continuous variable and in tertiles and compared between SLE patients and HC and associations with medication, disease activity and serological parameters were determined.ResultsAntibody levels were lower in 43 SLE patients compared to 40 HC (p < 0.001). There was no association between antibody levels and medication, lupus disease activity, vaccine type or prior COVID infection. Higher serum IgA, but not IgG or IgM, was associated with being in a higher anti-SARS-CoV-2 antibody level tertile (OR [95% CI] 1.820 [1.050, 3.156] p = 0.033). Similarly, higher lymphocyte count was also associated with being in a higher tertile of anti-SARS-CoV-2 (OR 3.330 [1.505, 7.366] p = 0.003).ConclusionPatients with SLE have lower antibody levels following 2 doses of COVID-19 vaccines compared to HC. In SLE lower lymphocyte counts and serum IgA levels are associated with lower antibody levels post vaccination, potentially identifying a subgroup of patients who may therefore be at increased risk of infection.
Project description:The folate receptor-positive circulating tumor cell (FR+-CTC) count can be used to improve the diagnosis rate of lung cancer. The lymphocyte count (LC) and derived neutrophil-to-lymphocyte ratio (dNLR) are involved in inflammatory processes. Whether the FR+-CTC count combined with the dNLR or LC is helpful for diagnosing lung cancer recurrence is not clear. Sixty-eight patients who were initially diagnosed with lung cancer and received first-line treatment were included. The clinicopathological characteristics, routine blood examination results and CTC examination results of the patients were collected. The role of the complete blood count and FR+-CTC count in lung cancer treatment response and prognosis was analyzed. The FR+-CTC count after treatment was significantly correlated with the T stage (p=0.005). Multivariate analysis showed that the pathological type and FR+-CTC count were independent predictors of disease-or progression-free survival (DFS/PFS) in patients with lung cancer (p=0.010 and p=0.030, respectively). The FR+-CTC count, LC and dNLR predicted the recurrence of lung cancer (sensitivity and specificity of the FR+-CTC count, 69.2% and 71.4%; the LC, 50.0% and 88.5%; and the dNLR, 50.0% and 88.1%, respectively). The FR+-CTC count combined with the LC or dNLR improved the diagnostic rate of lung cancer recurrence (sensitivity and specificity of the FR+-CTC count plus the LC, 53.8% and 90.5%, and the FR+-CTC count plus the dNLR, 73.1% and 73.8%, respectively). When these three indicators were combined to predict lung cancer recurrence, the AUC value was 0.817. The FR+-CTC count combined with the dNLR and/or LC after treatment can improve the diagnostic rate of lung cancer recurrence. A higher FR+-CTC count predicts worse DFS/PFS in patients with lung cancer.
Project description:The neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and absolute lymphocyte count/absolute monocyte count prognostic score (ALC/AMC PS) have been described as the most useful prognostic tools for patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed 148 Taiwanese patients with newly diagnosed diffuse large B-cell lymphoma under rituximab (R)-CHOP-like regimens from January 2001 to December 2010 at the Tri-Service General Hospital and investigated the utility of these inexpensive tools in our patients. In a univariate analysis, the NLR, LMR, and ALC/AMC PS had significant prognostic value in our DLBCL patients (NLR: 5-year progression-free survival [PFS], P = 0.001; 5-year overall survival [OS], P = 0.007. LMR: PFS, P = 0.003; OS, P = 0.05.PFS, P < 0.001; OS, P < 0.001). In a separate multivariate analysis, the ALC/AMC PS appeared to interact less with the other clinical factors but retained statistical significance in the survival analysis (PFS, P = 0.023; OS, P = 0.017). The akaike information criterion (AIC) analysis produced scores of 388.773 in the NLR, 387.625 in the LMR, and 372.574 in the ALC/AMC PS. The results suggested that the ALC/AMC PS appears to be more reliable than the NLR and LMR and may provide additional prognostic information when used in conjunction with the International Prognostic Index.
Project description:B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within 6 months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents antigen-loss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.
Project description:Chimeric antigen receptor T (CAR-T) cell targeting CD19 antigen has achieved exhilarative clinical efficacy in B-cell malignancies. However, challenges still remain for the currently approved anti-CD19 CAR-T therapies, including high recurrence rates, side effects and resistance. Herein, we aim to explore combinatorial therapy by use of anti-CD19 CAR-T immunotherapy and gallic acid (GA, an immunomodulatory natural product) for improving treatment efficacy. We assessed the combinatorial effect of anti-CD19 CAR-T immunotherapy with GA in cell models and a tumor-bearing mice model. Then, the underlying mechanism of GA on CAR-T cells were investigated by integrating network pharmacology, RNA-seq analysis and experimental validation. Furthermore, the potential direct targets of GA on CAR-T cells were explored by integrating molecular docking analysis with surface plasmon resonance (SPR) assay. The results showed that GA significantly enhanced the anti-tumor effects, cytokine production as well as the expansion of anti-CD19 CAR-T cells, which may be mainly through the activation of IL4/JAK3-STAT3 signaling pathway. Furthermore, GA may directly target and activate STAT3, which may, at least in part, contribute to STAT3 activation. Overall, the findings reported here suggested that the combination of anti-CD19 CAR-T immunotherapy with GA would be a promising approach to increase the anti-lymphoma efficacy.
Project description: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.
Project description:BackgroundAlthough most patients with classical Hodgkin's lymphoma (cHL) have a long survival duration, the current risk stratification is imperfect. A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is intriguing to investigate the significance of the ALC/AMC ratio in relation to tumor-associated macrophages (TAMs), yet another prognostic factor for cHL.MethodsWe examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in 312 cHL patients (median age, 37 years) using receiver operating characteristic curve analysis for optimal cutoff values, and compared these with TAM content.ResultsThe median follow-up was 65 months (range, 0.1-245 months). On univariate analysis, a low ALC/AMC ratio (<2.9) was correlated with a poorer overall survival (OS) outcome. A subgroup analysis of patients with limited-stage disease showed that the ALC/AMC ratio was significantly correlated with the OS time. Multivariate analysis showed the ALC/AMC ratio to be an independent prognostic factor for OS outcome. A Spearman correlation test of TAM content showed a negative correlation with the ALC/AMC ratio and a positive correlation with the peripheral blood macrophage percentage.ConclusionsThis study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor for OS outcome in patients with cHL and may have a role in the stratification of cHL patients in addition to the International Prognostic Score and TAM content.