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Asian Pacific Journal of Cancer... Dec 2023Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be...
INTRODUCTION
Allogeneic hematopoietic cell transplantation (allo-HCT) serves as a potentially curative intervention for various hematologic disorders. However, its utility can be limited by the emergence of chronic graft-versus-host disease (cGVHD). The clinical manifestations of cGVHD result from a complex immune response characterized by the involvement of both B and T cells. Ibrutinib, a pharmacological agent, acts as an inhibitor of Bruton's tyrosine kinase (BTK) pathway, which becomes activated through the B-cell receptor and regulates B-cell survival. By exerting inhibitory effects on both BTK and inhibitor of interleukin-2 inducible T-cell kinase (ITK), ibrutinib exhibits promise as a therapeutic approach for managing cGVHD. Ibrutinib may be considered as a viable treatment option for active cGVHD in cases where patients exhibit an inadequate response to corticosteroid-based therapies. This systematic review seeks to assess the efficacy and safety of ibrutinib in the context of cGVHD patient management.
METHOD
We incorporated search engines from PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. The study was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and Assessing The Methodological Quality of Systematic Review (AMSTAR). We used Risk of Bias- 2 (RoB-2) tool for assess the risk of bias in randomized controlled studies (RCTs) and Newcastle Ottawa Scale (NOS) for observational and open-label studies.
RESULTS
A total of 7 studies were included in this study consisted of four open-label studies, two retrospective cohort studies, and one RCT study. These studies compared Ibrutinitib with standard therapies. Two studies investigated the pediatric population, and five studies investigated the adult population. Overall, these studies reported the overall response rate (ORR) of ibrutinib for cGVHD were 54%-78%. The results showed that in pediatric patients, the ORR were 54-78%. The results also showed that in adult patients, the ORR were 67%-76%. The most common adverse effects observed across the seven studies included pyrexia, diarrhea, abdominal pain, cough, nausea, stomatitis, vomiting, headache, bleeding and bruising, infection, muscle aches, fatigue, oral bleeding, elevated transaminases, lower gastrointestinal bleeding, persistent dizziness, sepsis, pneumonia, reduced platelet count, exhaustion, sleeplessness, peripheral edema, and fatigue.
CONCLUSION
The majority of studies have indicated that ibrutinib exhibits a high ORR and provides long-lasting responses, while also having manageable side effects.
Topics: Adult; Humans; Child; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; B-Lymphocytes; Fatigue
PubMed: 38156834
DOI: 10.31557/APJCP.2023.24.12.4025 -
Blood Advances Feb 2024Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing... (Meta-Analysis)
Meta-Analysis
Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing studies of ibrutinib, another small molecule inhibitor, suggested that these agents may predispose to opportunistic infections. We sought to systematically review the randomized controlled trial (RCT) evidence of venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia. We systematically reviewed RCTs comparing venetoclax therapy with active or placebo controls for patients with hematologic malignancies. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis, and we computed the probability of any increased risk (P[risk ratio (RR) > 1]) of IAEs or neutropenic complications. Seven RCTs were included, comprising 2067 patients. In CLL (n = 1032), there was a low probability of increased risk of high-grade (P[RR > 1] = 71.2%) and fatal IAEs (P[RR > 1] = 64.5%) and high-grade neutropenia (P[RR > 1] = 63.4%). There were insufficient data to perform a meta-analysis of IAEs in AML; however, 1 trial suggested an increased risk of IAEs with venetoclax. Furthermore, in AML (n = 642), venetoclax was associated with a high probability of increased risk of high-grade neutropenia (P[RR > 1] = 94.6%) and febrile neutropenia (P[RR > 1] = 90.6%). Our results suggest that venetoclax has a low probability of increased risk of IAEs or neutropenia in CLL. By contrast, there is likely increased risk of high-grade neutropenia and febrile neutropenia in AML. Importantly, our analyses did not identify any specific IAEs that would benefit from routine antimicrobial prophylaxis or pre-emptive testing.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Communicable Diseases; Febrile Neutropenia; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38154071
DOI: 10.1182/bloodadvances.2023011964 -
Tropical Medicine & International... Feb 2024The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI) among people living with HIV (PLHIV).
METHODS
In this article, we systematically reviewed the evidence on the influence of probiotic supplementation on CD4 lymphocyte count, viral load and anaemia among PLHIV on highly active antiretroviral therapy (HAART) and those who were HAART-naive. Medical literature databases identified randomised trials and pre-post studies of probiotic supplementation and HIV-related outcomes, and random effects meta-analysis was conducted.
RESULTS
The preponderance of the evidence suggests that probiotic supplementation only improved CD4 lymphocyte count modestly, with quantitatively greater impact among individuals who were HAART-naive compared to HAART-experienced individuals. Probiotic supplementation improved CD4 lymphocyte count by 53 cells/mm (95% CI: 22 to 85) from 18 studies. Probiotic supplementation however reduced haemoglobin concentration by -2.1 g/L (95% CI: -4.0 to -0.2). Although viral load remain unchanged in HAART-experienced participants following probiotic supplementation, HAART-naïve participants saw a decrease in viral load. There were too few studies on the impact of probiotic supplementation on viral load (N = 1).
CONCLUSION
Probiotic supplementation resulted in a modest increase in CD4 lymphocyte count among HAART-naive individuals with no significant change observed among HAART-experienced ones. Viral load and haemoglobin concentration also remained unchanged following probiotic supplementation. Further rigorous and well-powered studies may evaluate the effect of probiotic supplementation on important clinical outcomes among PLHIV on HAART.
Topics: Humans; HIV Infections; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Probiotics; Anemia; Hemoglobins; Viral Load
PubMed: 38112243
DOI: 10.1111/tmi.13955 -
Skin Health and Disease Dec 2023Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed... (Review)
Review
Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein (anti-CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule found on natural killer cells and activated T-cells which negatively regulates T-cell proliferation and function. LAG-3 inhibitors interact with LAG-3 ligands on the surface of T-cells to block T-regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T-cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG-3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG-3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG-3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.
PubMed: 38047262
DOI: 10.1002/ski2.296 -
Cancer Cell International Dec 2023Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in... (Review)
Review
BACKGROUND
Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors.
METHODS
Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells.
RESULTS
A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01-1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96-2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90-1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81-1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers.
CONCLUSIONS
Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.
PubMed: 38041068
DOI: 10.1186/s12935-023-03157-5 -
Medicinal Research Reviews Mar 2024Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3... (Review)
Review
Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.
Topics: Humans; Lysine; Histone Demethylases; Monoamine Oxidase Inhibitors; Histones; Neoplasms; Drug Discovery; Enzyme Inhibitors
PubMed: 38014919
DOI: 10.1002/med.22000 -
Rheumatology and Therapy Feb 2024Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment...
INTRODUCTION
Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment approaches. This meta-analysis aims to assess the efficacy and safety of low-dose interleukin-2 (LD-IL-2) and evaluate the alterations in lymphocyte subsets in various rheumatic diseases following administration of different dosages of LD-IL-2.
METHODS
A comprehensive search was conducted in PubMed, Web of Science, the Cochrane Library, Embase databases and CNKI to identify relevant studies. A total of 31 trials were included in this meta-analysis. The review protocols were registered on PROSPERO (CRD42022318916), and the study followed the PRISMA guidelines.
RESULTS
Following LD-IL-2 treatment, patients with ARDs exhibited a significant increase in the number of Th17 cells and Tregs compared to their pre-treatment levels [standardized mean difference (SMD) = 0.50, 95% confidence interval (CI) (0.33, 0.67), P < 0.001; SMD = 1.13, 95% CI (0.97, 1.29), P < 0.001]. Moreover, the Th17/Tregs ratio showed a significant decrease [SMD = - 0.54, 95% CI (- 0.64, - 0.45), P < 0.001]. In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), LD-IL-2 injection led to a significant increase in Treg numbers, and the Th17/Tregs ratio and disease activity scores, including Disease Activity Score-28 joints (DAS28), Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), were all significantly reduced. No serious adverse events were reported in any of the included studies. Additionally, 54.8% of patients with lupus nephritis achieved distinct clinical remission following LD-IL-2 treatment. Injection site reactions and fever were the most common side effects of LD-IL-2, occurring in 33.1% and 14.4% of patients, respectively.
CONCLUSION
LD-IL-2 treatment showed promise and was well tolerated in the management of ARDs, as it effectively promoted the proliferation and functional recovery of Tregs.
TRIAL REGISTRATION
Retrospectively registered (CRD42022318916, 21/04/2022).
PubMed: 37980696
DOI: 10.1007/s40744-023-00620-7 -
Medicine Nov 2023Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA) patients could be improved by DJD. However, the existing evidence was not robust enough and controversial.
METHODS
Randomized controlled trials of DJD for RA were retrieved from Chinese and English databases from their inception to April 16, 2023. Meta-analysis was performed by Stata 17 software. We used subgroup analysis, meta-regression, and sensitivity analysis to identify potential sources of heterogeneity. The subgroup analysis and meta-regression were conducted from 6 aspects, including age, course of disease, course of treatment, interventions used in the experimental or control group, and random sequence generation. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger's test and funnel plots when the number of relevant studies was greater than or equal to 10.
RESULTS
Forty-two studies were included, involving 3635 patients and 19 outcome indicators. Meta-analysis showed that, compared with the routine disease-modifying antirheumatic drugs (rDMARDs), DJD could better improve the level of laboratory indicators, main symptoms and signs, and questionnaire scores of RA patients. The laboratory indicators included rheumatoid factor, T lymphocyte subpopulation (including CD4+, CD8+, and CD4+/CD8+), and inflammatory biomarkers (including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor-α, interleukin 6, interleukin 1β, and interleukin 1). The main symptoms and signs included the duration of morning stiffness, the number of joint tenderness, the number of swollen joints, and the grip strength of both hands. The questionnaire included visual analogue scale, health assessment questionnaire, and disease activity score in 28 joints. In addition, the adverse events of DJD treatment were significantly lower than those of rDMARDs. However, the results of a few subgroup analyses differed from the overall results. Furthermore, the publication bias assessment showed that, out of 11 evaluated results, 4 had publication bias.
CONCLUSION
DJD could be a satisfactory complementary and alternative therapy for RA. However, due to a small number of subgroup analysis results being different from the overall results, it should be verified by further studies.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Hand Strength; Randomized Controlled Trials as Topic
PubMed: 37933004
DOI: 10.1097/MD.0000000000035513 -
Biomedicines Oct 2023Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are... (Review)
Review
BACKGROUND
Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy.
MATERIALS AND METHODS
The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases.
RESULTS
2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study.
CONCLUSIONS
Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.
PubMed: 37893096
DOI: 10.3390/biomedicines11102722 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364