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1.
J Pediatr Hematol Oncol ; 45(1): e145-e149, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36598967

RESUMO

Rituximab (RTX) is widely employed to treat Epstein-Barr virus reactivation in children undergoing Hematopoietic Cell Transplantation (HCT). The resulting loss of B cells may cause persistent hypogammaglobulinemia. This retrospective cross-sectional study aims to identify flow cytometry biomarkers associated with persistent hypogammaglobulinemia in patients receiving RTX after HCT. We analyzed 5 patients (cases group) requiring immunoglobulin substitution due to low level of IgG (IgG <5 g/L) detected after RTX treatment and 5 patients (controls group) not requiring long-term immunoglobulin (Ig) substitution. We investigated the B cell reconstitution, and in patients group we observed a significantly lower count in B total, IgD+CD27+ marginal B cells and IgD-CD27+ switched-memory B cells, after a median of 5 years from HCT, compared with the control group. Despite the importance limits of our study and the heterogeneity of our data (age of included patients, time of evaluation, interval between RTX dose and assessment) we conclude that RTX given early after HCT might cause a deranged B cell maturation, contributing to the delation in B cell recovery following HCT, and switched memory and marginal zone B cell counts could be a promising biomarker to identify patients requiring long-term Ig substitution.


Assuntos
Agamaglobulinemia , Subpopulações de Linfócitos B , Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Rituximab/uso terapêutico , Agamaglobulinemia/terapia , Agamaglobulinemia/induzido quimicamente , Estudos Retrospectivos , Estudos Transversais , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/etiologia , Anticorpos Monoclonais Murinos/uso terapêutico , Herpesvirus Humano 4 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Biomarcadores , Imunoglobulina G
2.
Indian J Ophthalmol ; 71(1): 146-152, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588225

RESUMO

Purpose: To describe the clinical features and management of patients with scleritis associated with granulomatosis with polyangiitis (GPA) at a tertiary eye care center in South India. Methods: The clinical profile and management of patients presenting to a tertiary eye care center in South India with scleritis secondary to GPA from 2003 to 2021 were analyzed retrospectively. Scleritis was classified into anterior diffuse, nodular, and necrotizing scleritis with inflammation according to Watson and Hayreh's classification. Demographic characteristics, clinical features, anti-neutrophil cytoplasmic antibody (ANCA) positivity, treatment response, ocular complications, and status at the last follow-up were analyzed. Statistical analysis of data was performed using Microsoft Excel 2019. Results: Nineteen eyes of 17 patients (15 cytoplasmic staining ANCA [c-ANCA], two p-ANCA positive) were included. Fifteen eyes had necrotizing scleritis, two had diffuse anterior scleritis, and two had nodular scleritis. Remission was induced using a combination of steroids and cyclophosphamide or rituximab. Maintenance therapy was instituted using tapering steroids and immunosuppressants like cyclophosphamide, mycophenolate mofetil, methotrexate, or rituximab. Three eyes required a scleral patch graft. Fourteen patients had good anatomical and visual outcomes, and three were lost to follow-up. Conclusion: GPA is a rare disease, while it is the most common ANCA-associated vasculitis with scleritis. As scleritis may be the presenting sign of the disease, ophthalmologists must be aware of the various features suggestive of GPA. GPA-associated scleritis can have a good prognosis when diagnosed promptly and managed aggressively in the acute stage, and remission is maintained with adequate systemic immunosuppression.


Assuntos
Granulomatose com Poliangiite , Esclerite , Humanos , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Esclerite/etiologia , Rituximab/uso terapêutico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapia , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Centros de Atenção Terciária , Ciclofosfamida/uso terapêutico
3.
PLoS One ; 18(1): e0278873, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607896

RESUMO

Monoclonal Antibodies (mAbs) are being used in the treatment of both malignant and non-malignant diseases and whilst highly effective, certain products have very short expiry times. Clinical deterioration and supply chain disruption can often lead to wastage and there is a need to reduce this by improving efficiency in logistics practices between manufacturing sites and administration locations. This study aimed to investigate the influence of drone flight on the stability of cancer medicines. Clinically expired, premanufactured monoclonal antibodies (mAbs) were investigated, contained inside instrumented Versapaks, and flown in a Skylift (Mugin) V50 vertical take-off and landing drone through seven phases of flight, (take-off, hover, transition, cruise, transition, hover, and landing). Storage specifications (2-8°C) were met, and any vibrations emanating from the drone and transmitted through the packaging during flight were monitored using accelerometers. Vibration occurred largely above 44 Hz which was consistent with rotor speeds during operation and was significantly greater in amplitude during transition than in forward flight or in hover. Bench experiments validated assurance practices, exploring the edge-of-quality failure by applying extremes of rotational vibration to the mAbs. Aggregation and fragmentation represented a loss of quality in the mAbs and would pose a risk to patient safety. No significant difference was identified in the aggregation and fragmentation of all flown mAbs samples, indicating structural integrity. Flown mAbs in their infusion bags had similar particle sizes compared to controls, (Bevacizumab 11.8±0.17 nm vs. 11.6±0.05 nm, Trastuzumab 11.2±0.05 nm vs. 11.3±0.13 nm, Rituximab 11.4±0.27 nm vs. 11.5±0.05 nm) and aggregate content (Bevacizumab 1.25±0.03% vs 1.32±0.02% p = 0.11, Trastuzumab 0.15±0.06% vs. 0.16±0.06% p = 0.75, Rituximab 0.11±0.02% vs. 0.11±0.01% p = 0.73). The quality of the three mAbs was assured, suggesting that the V50 drone did not induce sufficient levels of vibration to adversely affect their quality.


Assuntos
Neoplasias , Dispositivos Aéreos não Tripulados , Humanos , Bevacizumab/uso terapêutico , Rituximab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Trastuzumab/uso terapêutico , Neoplasias/tratamento farmacológico
4.
Pediatr Rheumatol Online J ; 21(1): 3, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609397

RESUMO

BACKGROUND: Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking. METHODS: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher's exact test was used to compare the distribution of responses to each survey question. RESULTS: One hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1-2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience. CONCLUSION: Most respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices.


Assuntos
Antirreumáticos , Artrite Juvenil , Dermatomiosite , Reumatologia , Humanos , Criança , Metotrexato/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Dermatomiosite/diagnóstico , Rituximab/uso terapêutico , Estudos Prospectivos , Antirreumáticos/uso terapêutico , Glucocorticoides/uso terapêutico
5.
Am J Hematol ; 98(2): 348-358, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36588395

RESUMO

DISEASE OVERVIEW: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in most IgM MGUS patients. MYD88 is not required for the diagnosis. RISK STRATIFICATION: Age, hemoglobin level, platelet count, ß2 microglobulin, LDH, and monoclonal IgM concentrations are characteristics that are predictive of outcomes. RISK-ADAPTED THERAPY: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or a BTK inhibitor. The preferred Mayo Clinic induction is either rituximab and bendamustine (without rituximab maintenance) or zanubrutinib. MANAGEMENT OF REFRACTORY DISEASE: Bortezomib, cyclophosphamide, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, bendamustine, and venetoclax have all been shown to have activity in relapsed WM. Given WM's natural history, the reduction of therapy toxicity is an important part of treatment selection.


Assuntos
Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Rituximab/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Fator 88 de Diferenciação Mieloide/genética , Anticorpos Monoclonais/uso terapêutico , Paraproteínas , Medição de Risco , Imunoglobulina M
6.
Saudi Med J ; 44(1): 38-44, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36634942

RESUMO

OBJECTIVES: To investigate the clinicopathological features, insulin resistance (IR) status, and the outcomes of populations with diffuse large B-cell lymphoma (DLBCL) of the breast. METHODS: This study was carried out at Department of Haematology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, that included 32 patients treated form January 2009 to June 2020. The primary endpoints of the study were their survival time. RESULTS: There were 32 patients in the study. A total of 18 (56.2%) patients had IR. In terms of treatment, 31.2% were treated with surgery, most (93.8%) received chemotherapy, and 25% received radiotherapy and intrathecal therapy. Univariate analysis indicated the patients with stages III-IV, B symptoms, tumour recurrence, PAX5 positivity, and c-MYC positivity showed a shorter survival time (p<0.05). The overall survival and progression-free survival (PFS) rates in IR group were shorter than those without IR, but there was no statistical difference (p>0.05). Multivariate analysis indicated that tumour recurrence shortened the 5-year PFS of the patients (p=0.037). CONCLUSION: Primary DLBCL of the breast was very rare; more than half of the cases had IR, but IR did not affect their survival.


Assuntos
Resistência à Insulina , Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Prognóstico , Recidiva Local de Neoplasia/epidemiologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rituximab
7.
Cell Commun Signal ; 21(1): 16, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691066

RESUMO

BACKGROUND: Aggressive B-cell non-Hodgkin's lymphoma (B-NHL) patients often develop drug resistance and tumor recurrence after conventional immunochemotherapy, for which new treatments are needed. METHODS: We investigated the antitumor effects of CBL0137. In vitro, cell proliferation was assessed by CCK-8 and colony formation assay. Flow cytometry was performed to analyze cell cycle progression, apoptosis, mitochondrial depolarization, and reactive oxygen species (ROS) production. Autophagy was detected by transmission electron microscopy and mGFP-RFP-LC3 assay, while western blotting was employed to detect proteins involved in apoptosis and autophagy. RNA-sequencing was conducted to analyze the transcription perturbation after CBL0137 treatment in B-NHL cell lines. Finally, the efficacy and safety of CBL0137, rituximab, and their combination were tested in vivo. RESULTS: CBL0137, a small molecule anticancer agent that has significant antitumor effects in B-NHL. CBL0137 sequesters the FACT (facilitates chromatin transcription) complex from chromatin to produce cytotoxic effects in B-NHL cells. In addition, we discovered novel anticancer mechanisms of CBL0137. CBL0137 inhibited human B-NHL cell proliferation by inducing cell cycle arrest in S phase via the c-MYC/p53/p21 pathway. Furthermore, CBL0137 triggers ROS generation and induces apoptosis and autophagy in B-NHL cells through the ROS-mediated PI3K/Akt/mTOR and MAPK signaling pathways. Notably, a combination of CBL0137 and rituximab significantly suppressed B-NHL tumor growth in subcutaneous models, consistent with results at the cellular level in vitro. CONCLUSIONS: CBL0137 has potential as a novel approach for aggressive B-NHL, and its combination with rituximab can provide new therapeutic options for patients with aggressive B-NHL. Video Abstract.


Assuntos
Antineoplásicos , Linfoma de Células B , Humanos , Rituximab/farmacologia , Rituximab/uso terapêutico , Espécies Reativas de Oxigênio , Fosfatidilinositol 3-Quinases , Recidiva Local de Neoplasia , Linfoma de Células B/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose , Autofagia , Cromatina , Linhagem Celular Tumoral
8.
Pharmacogenomics ; 24(1): 59-68, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36661028

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin lymphoma. There is great heterogeneity in its molecular biological characteristics, clinical manifestations and prognosis. The use of rituximab has greatly improved the cure rate of DLBCL, but there are still 30% of patients with poor prognosis. In the era of precision medicine, the significance of molecular biology and genetic factors on the diagnosis, treatment and prognosis of patients has been found. Among these, next-generation sequencing technology plays an important role. This paper reviews the research progress of next-generation sequencing technology in the classification, diagnosis, prognosis and molecular targeted therapy of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Rituximab/genética , Rituximab/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Prognóstico , Sequenciamento de Nucleotídeos em Larga Escala , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
10.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649512

RESUMO

BACKGROUND: Presently, several classification methods are based on diffuse large B-cell lymphoma (DLBCL), but its clinical application has not yet been testified in Asian populations. METHODS: Twenty-five DLBCL patients were subjected to second-generation gene sequencing (NGS), and retrospective analysis of clinical features of the patients was to explore genotyping and survival prognosis biomarkers. RESULTS: The prevalent mutant genes in DLBCL patients cover myeloid differentiation factor 88 (MyD88) (40%), TP53 (32%), B-cell translocation gene 2 (BTG2) (28%), PIM1 (28%), and CREB-binding protein (CREBBP) (24%) in this study. The classical International Prognostic Index (IPI) scores were associated with progression-free survival (PFS) (HR: 7.52, 95% CI 1.51 - 37.6, p = 0.00393) via univariate analysis. Furthermore, patients with ETS-variant gene 6 (ETV6) (HR: 5.1, 95% CI 0.927 - 28.1, p = 0.0371), platelet-derived growth factor receptor A (PDGFRA) (HR: 4.29, 95% CI 0.824 - 22.3, p = 0.0594), platelet-derived growth factor receptor B (PDGFRB) (HR: 10.8, 95% CI 0.979 - 119, p = 0.0149) was distinctively correlated with poor PFS except for the IPI score. Nevertheless, the mutation of PDGFRA/B gene was not distinct in further multivariate analysis (PFS: HR: 2.72, 95% CI 0.52 - 14.23, p = 0.2369). Additionally, better survival prognosis was in DLBCL patients who did not progress within 12 months (POD12). Ultimately, caspase recruitment domain 11 (CARD11) gene mutations were enriched in patients with primary intranodal tumors, but the prognostic relevance was not discovered. CONCLUSIONS: ETV6 and platelet-derived growth factor receptor (PDGFR)A/B gene mutations are supposed to be potential biomarkers for the prognosis of DLBCL patients via the statistical analysis of this small sample, and POD12 is also expected to be an effective endpoint for efficacy assessment.


Assuntos
Proteínas Imediatamente Precoces , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Prognóstico , Biomarcadores , Receptores do Fator de Crescimento Derivado de Plaquetas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prednisona/uso terapêutico , Proteínas Imediatamente Precoces/uso terapêutico , Proteínas Supressoras de Tumor
11.
Medicine (Baltimore) ; 102(4): e32801, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705370

RESUMO

RATIONALE: The coexistence of the extranidal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) and multiple myeloma (MM) is an exceedingly rare situation. The rare situation precludes any evidence-based guidelines for MZL or MM. PATIENT CONCERNS AND DIAGNOSES: We presented a unique case of the coexistence of primary mediastinal MALT lymphoma and MM like polyneuropathy, organomegaly, endocrinopathy, M-protein, skin syndrome. INTERVENTIONS AND OUTCOMES: The patient was first diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin syndrome in the department of neurology, then MM in the department of hematology, and the mediastinal MALT simultaneously coexisting with MM was found by biopsy in the department of thoracic surgery. The patient received combination therapy with rituximab and bortezomib followed by lenalidomide maintenance. To understand MZL lymphoma with plasmacytic differentiation better, we analyzed cases of MZL lymphomas with plasma cell neoplasms. Most of these cases were MZL lymphomas with light chain-restricted plasmacytic differentiation. The lymphomas relapsed with plasma cell neoplasms or transformed into plasma cell neoplasms after anti-lymphoma therapy. LESSONS: The case demonstrated clinical complexity and the importance of the detailed assessment. The case and literature review demonstrated the value of detecting light chain-restricted plasmacytic differentiation for the treatment of MZL lymphoma with rituximab plus lenalidomide or bortezomib.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Mieloma Múltiplo , Síndrome POEMS , Neoplasias do Timo , Humanos , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Rituximab/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Lenalidomida/uso terapêutico , Síndrome POEMS/complicações , Síndrome POEMS/diagnóstico , Bortezomib/uso terapêutico
12.
Adv Clin Exp Med ; 32(1): 131-136, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36603138

RESUMO

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.


Assuntos
COVID-19 , Linfoma Folicular , Humanos , Pessoa de Meia-Idade , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/etiologia , Linfoma Folicular/patologia , Rituximab/efeitos adversos , Estudos Retrospectivos , Polônia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina
13.
BMJ Open ; 13(1): e064220, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36657752

RESUMO

INTRODUCTION: Primary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Rituximab has been recommended in the treatment of PMN by the updated Kidney Disease Improved Outcome guideline. However, the optimal dosing regimen of rituximab for the initial treatment of patients with PMN is unclear. METHODS AND ANALYSIS: A comprehensive screening will be performed by searching PubMed, Embase and the CENTRAL (Cochrane Central Register of Controlled Trials) without language restriction. Studies evaluating the efficacy of rituximab monotherapy using the following types of dosing regimens will be included: high-dose regimen; standard regimen and low-dose regimen. Studies with less than 10 participants will be excluded. The primary outcome is the remission rate at 12 months. The secondary outcomes are remission rate at 6 and 24 months, complete remission rate at 6, 12 and 24 months, relapse at 6, 12 and 24 months, and side effects. Risk of Bias In Non-randomised Studies of Interventions tool will be used to assess the risk of bias for non-randomised studies and the Cochrane risk of bias assessment tool will be used for randomised controlled trials. The pooled remission rate, complete remission rate, relapse rate and side effects will be estimated using the metaprop command. All analyses will be calculated using Stata software (V.15.0; StataCorp). ETHICS AND DISSEMINATION: Ethics approval is not required. The results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42022319401.


Assuntos
Glomerulonefrite Membranosa , Nefropatias , Síndrome Nefrótica , Adulto , Humanos , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Nefropatias/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Controlados não Aleatórios como Assunto
14.
BMC Neurol ; 23(1): 47, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709264

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) considers a rare cause of ischemic stroke (IS). We reported a case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP), in whom two IS events developed during 48 h. CASE PRESENTATION: A 59-year-old diabetic male was presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan was performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient was not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient's neurological condition deteriorated, and the second brain CT scan showed new ischemic lesions in the left MCA territory. Initial laboratory evaluation indicated thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progressed, and microangiopathic hemolytic anemia (MAHA) developed. The ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent plasma exchange activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent and pulse IV methylprednisolone. Rituximab was also added due to the refractory course of the disease. After a prolonged hospital course, he had considerable neurologic recovery and was discharged. CONCLUSIONS: Clinicians should consider two points. First, TTP should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Second, worsening the patient's condition during hospitalization may indicate a new stroke and should be investigated immediately.


Assuntos
Anemia , AVC Isquêmico , Púrpura Trombocitopênica Trombótica , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , AVC Isquêmico/terapia , Rituximab , Troca Plasmática , Anemia/terapia
15.
PLoS One ; 18(1): e0280044, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36630466

RESUMO

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.


Assuntos
Infecções por HIV , Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Monócitos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , África do Sul/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Vincristina/uso terapêutico , Contagem de Leucócitos , Prednisona/uso terapêutico , Infecções por HIV/tratamento farmacológico
16.
BMC Cancer ; 23(1): 74, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690960

RESUMO

BACKGROUND: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review. METHODS: Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an alkylating agent, in combination or separately. Overall response rate (ORR) and complete response (CR) were estimated using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) estimated by reconstructing digitized curves using the Guyot algorithm, and survival analyses were conducted, stratified by ≥2 prior LOT and ≥ 3 prior LOT groups (as defined in the source material). Restricting the analyses to the observational cohorts was investigated as a sensitivity analysis. RESULTS: The analysis-set included 20 studies published between 2014 and 2021. Studies were primarily US and/or European based, with the few exceptions using treatments approved in US/Europe. The estimated ORR was 58.47% (95% confidence interval [CI]: 51.13-65.62) and proportion of patients with CR was 19.63% (95% CI: 15.02-24.68). The median OS among those ≥2 prior LOT was 56.57 months (95% CI: 47.8-68.78) and median PFS was 9.78 months (95% CI: 9.01-10.63). The 24-month OS decreased from 66.50% in the ≥2 prior LOT group to 59.51% in the ≥3 prior LOT group, with a similar trend in PFS at 24-month (28.42% vs 24.13%). CONCLUSIONS: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of treated patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by treatments currently available in the US and Europe.


Assuntos
Antineoplásicos , Linfoma Folicular , Adulto , Humanos , Linfoma Folicular/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Intervalo Livre de Progressão , Rituximab/uso terapêutico
17.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674612

RESUMO

Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative inborn error of immunity (IEI) characterized by DNA repair defect, chromosomal instability, and hypersensitivity to ionizing radiation. Impaired DNA double-strand break repair determines a high risk of developing hematological malignancies, especially lymphoproliferative diseases. Poor response to treatment, excessive chemotherapy toxicities, and the need for avoiding exposure to ionizing radiation make the successful clinical management of patients with AT challenging for oncologists. We describe the favorable outcome of the LBCL with IRF4 rearrangement at stage III in a 7-year-old female patient diagnosed with AT. The patient was treated according to the B-HR arm of the INTER-B-NHL-COP 2010 protocol, including the administration of rituximab, cyclophosphamide, methotrexate, prednisone, etc. She presented excessive treatment toxicities despite individually reduced doses of methotrexate and cyclophosphamide. However, in the MRI there was no significant reduction in pathologic lymph nodes after three immunochemotherapy courses. Therefore, a lymph node biopsy was taken. Its subsequent histopathological examination revealed tuberculosis-like changes, though tuberculosis suspicion was excluded. After two following immunochemotherapy courses, PET-CT confirmed complete remission. From March 2022 onwards, the patient has remained in remission under the care of the outpatient children's oncology clinic.


Assuntos
Ataxia Telangiectasia , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Criança , Metotrexato/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rituximab/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/genética , Prednisona/uso terapêutico , Ciclofosfamida/uso terapêutico , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/genética
18.
In Vivo ; 37(1): 493-497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593046

RESUMO

BACKGROUND/AIM: To date, no reports of interleukin (IL)-5-producing Castleman disease with nephrotic syndrome and moreover no reports of relapse after remission with rituximab treatment, have been published. CASE REPORT: A 67-year-old male presented to the Osaka Medical and Pharmaceutical University Hospital with a history of low-grade fever, papules, and nephrotic syndrome. Lymph nodes were palpated in the inguinal region. The patient showed anemia, eosinophilia, polyclonal hypergammaglobulinemia, and elevated interleukin (IL)-6 levels. Patient's serum IL-5 and IL-6 levels were measured using ELISA and immunohistochemical staining of lymph nodes was performed with antibodies specific to CD134. Histological examination confirmed diagnosis of a plasma cell variant of Castleman disease. After a total of four weekly doses of rituximab, urinary protein disappeared, and skin symptoms improved. However, one month after rituximab treatment, the skin rash worsened again, and eosinophils and IL-5 were elevated significantly. CONCLUSION: This is the first report of recurrent Castleman disease with direct evidence of increased serum IL-5. It may be reasonable to use rituximab, an anti-CD20 antibody for treating the disease, however, for IL-5-producing cases the effect of rituximab may be partial.


Assuntos
Hiperplasia do Linfonodo Gigante , Síndrome Nefrótica , Masculino , Humanos , Idoso , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Rituximab/uso terapêutico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Interleucina-5/uso terapêutico , Anticorpos
19.
Sci Rep ; 13(1): 1438, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697456

RESUMO

Efforts have been made to improve the risk stratification model for patients with diffuse large B-cell lymphoma (DLBCL). This study aimed to evaluate the disease prognosis using machine learning models with iterated cross validation (CV) method. A total of 122 patients with pathologically confirmed DLBCL and receiving rituximab-containing chemotherapy were enrolled. Contributions of clinical, laboratory, and metabolic imaging parameters from fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans to the prognosis were evaluated using five regression models, namely logistic regression, random forest, support vector classifier (SVC), deep neural network (DNN), and fuzzy neural network models. Binary classification predictions for 3-year progression free survival (PFS) and 3-year overall survival (OS) were conducted. The 10-iterated fivefold CV with shuffling process was conducted to predict the capability of learning machines. The median PFS and OS were 41.0 and 43.6 months, respectively. Two indicators were found to be independent predictors for prognosis: international prognostic index and total metabolic tumor volume (MTVsum) from FDG PET/CT. For PFS, SVC and DNN (both with accuracy 71%) have the best predictive results, of which outperformed other algorithms. For OS, the DNN has the best predictive result (accuracy 76%). Using clinical and metabolic parameters as input variables, the machine learning methods with iterated CV method add the predictive values for PFS and OS evaluation in DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Prognóstico , Rituximab/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 51-59, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655664

RESUMO

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS: The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.


Assuntos
Linfoma de Células B , Criança , Adolescente , Humanos , Rituximab/efeitos adversos , Linfoma de Células B/tratamento farmacológico , Intervalo Livre de Progressão , Indução de Remissão , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
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