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Objective:To investigate the clinical efficacy and safety of ZR2 (zevalin + lenalidomide + rituximab) regimen in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was conducted. The clinical data of 16 elderly (>65 years old) non-germinal center B-cell-like DLBCL patients treated with ZR2 regimen at the Taixing People's Hospital from January 2021 to March 2023 were retrospectively analyzed. The efficacy, adverse reactions and prognosis of patients were observed.Results:Of the 16 patients, 11 were male and 5 were female, with the age [ M ( Q1, Q3)] of 76 years old (70 years old, 78 years old), and 10 cases were Ann Arbor stage Ⅲ-Ⅳ. Among the 16 patients, 9 achieved complete remission, 4 patients achieved partial remission. All 16 patients experienced varying degrees of reversible bone marrow suppression, grade Ⅲ-Ⅳ hematologic adverse reactions included neutropenia (7 cases) and thrombocytopenia (2 cases), and the bone marrow hematopoiesis recovered after treatment with granulocyte colony-stimulating factor and thrombopoietin. The main ≥grade Ⅱ non-hematologic adverse reactions were gastrointestinal reactions (5 cases), liver function abnormalities (3 cases) and peripheral neuropathy (2 cases), which were improved after the appropriate treatment. Two patients discontinued the treatment of this regimen due to disease progression, and 1 patient died from complications after 2 cycles of treatment. No deep vein thrombosis, cardiac toxicity or renal toxicity occurred during the treatment process. Conclusions:The ZR2 regimen is effective in the treatment of elderly DLBCL patients with tolerable adverse reactions.
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Objective:To investigate the efficacy and safety of Rituximab (RTX) in the treatment of children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) and to analyze the factors influencing the efficacy.Methods:Case series study.The clinical data of children with FRNS/SDNS who received B-cell-guided RTX (single dose: 375 mg/m 2, maximum dose: 500 mg, one additional dose when peripheral blood CD19 + B lymphocytes ≥0.01) in the First Affiliated Hospital of Zhengzhou University from September 2019 to March 2022 were retrospectively collected.The frequency of relapse and cumulative dose of glucocorticoids before and after RTX treatment were compared.The Kaplan-Meier method was used to analyze relapse-free survival rate and FRNS/SDNS-free survival rate after RTX treatment.The influencing factors of relapse were analyzed using the Cox proportional hazards regression model. Results:Totally 47 children were enrolled, including 35 males and 12 females; the age of first application of RTX was 10.2 (6.9, 13.0) years; 33 children had used one type of immunosuppressant before, and 14 children had used two or more types of immunosuppressant before; the dose of RTX treatment was 3.0 (2.0, 3.0). The frequency of relapse[0(0, 0.55) times/year vs.1.62 (1.09, 2.40) times/year] and cumulative dose of glucocorticoids[0.12 (0.05, 0.21) mg/(kg·d) vs.0.40 (0.20, 0.56) mg/(kg·d)] after RTX treatment significantly decreased compared with previous immunosuppressive treatment ( Z=-5.56, -5.54, all P<0.001). The relapse-free survival rates at 6, 12, 18 and 24 months after treatment were 80.9%, 72.3%, 68.1% and 68.1%, respectively, and the FRNS/SDNS-free survival rates were 93.6%, 89.4%, 89.4% and 89.4%, respectively.Univariate Cox regression analysis showed that the high frequency of relapse during previous immunosuppressive therapy was a risk factor for relapse after RTX treatment ( P<0.05). Of the 14 children who relapsed, 6 occurred in children whose CD19 + B lymphocytes<0.01, and the frequency of relapse after RTX treatment was significantly higher than those whose CD19 + B lymphocytes≥0.01 ( Z=-2.84, P=0.005). No severe adverse reactions occurred during RTX treatment and follow-up. Conclusions:The B-cell-guided RTX is effective and safe in the treatment of FRNS/SDNS in children.The high frequency of relapse during previous immunosuppressive therapy is a risk factor for relapse after RTX treatment, and relapse in the state of B lymphocyte depletion predicts poor outcomes of RTX treatment.
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Objective:To evaluate the clinical efficacy of rituximab injection combined with CHOP regimen (cyclophosphamide+doxorubicin+vincristine+prednisolone) in the treatment of diffuse large B-cell lymphoma (DLBCL).Methods:One hundred and twenty patients with DLBCL who treatment in the First Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2022 were selected as the study object. They were randomly divided into the study group (60 cases) and the control group (60 cases). The control group was treated with CHOP regimen, and the study group was treated with rituximab injection on the basis of CHOP regimen. The clinical efficacy, inflammatory reaction, immune function and adverse reaction were evaluated after 6 courses of treatment.Results:After treatment, the total clinical effective rate in the study group was higher than that in the control group: 88.33%(53/60) vs. 70.00%(42/60), there was statistical difference ( χ2 = 6.11, P<0.05). Before treatment, the levels of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IL-6 and TNF-α were decreased, and the levels of serum IL-6 and TNF-α in the study group were lower than those in the control group: (223.56 ± 21.28) ng/L vs. (267.35 ± 25.36) ng/L, (9.34 ± 2.75) μg/L vs. (11.96 ± 3.83) μg/L, there were statistical differences ( P<0.05). Before treatment, the levels of serum immunoglobulin (Ig) A, IgM and IgG in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IgA, IgM and IgG were decreased, but the levels of serum IgA, IgM and IgG in the study group were higher than those in the control group: (1.83 ± 0.46) g/L vs. (1.34 ± 0.34) g/L, (1.15 ± 0.22) g/L vs. (0.83 ± 0.24) g/L, (10.67 ± 1.65) g/L vs. (8.02 ± 1.62) g/L, there were statistical differences ( P<0.05). After treatment, the incidence of thrombocytopenia, leucopenia, gastrointestinal reaction, bone marrow suppression and liver function injury in the study group were lower than those in the control group: 6.67%(4/60) vs. 20.00%(12/60), 15.00%(9/60) vs. 31.67%(19/60), 30.00%(18/60) vs. 58.33%(35/60), 5.00%(3/60) vs. 16.67%(10/60), 10.00%(6/60) vs. 25.00%(15/60), there were statistical differences ( χ2 = 4.62, 4.66, 9.77, 4.33, 4.88, P<0.05). Conclusions:The treatment effect of rituximab injection combined with CHOP regimen in DLBCL is significant, which can reduce the inflammatory reaction of the body, reduce the damage of immune function, and reduce the adverse reactions of chemotherapy.
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With rapid development of organ transplantation, the issue of global organ shortage has become increasingly prominent. At present, liver transplantation is the most effective treatment for end-stage liver disease. Nevertheless, the shortage of donors has been a key problem restricting the development of liver transplantation. China is a country with a larger number of hepatitis B, and the shortage of donor liver is particularly significant. Many critically ill patients often lose the best opportunity or even die because they cannot obtain a matched donor liver in time. As a strategy to expand the donor pool, ABO-incompatible (ABOi) liver transplantation offers new options for patients who are waiting for matched donors. However, ABOi liver transplantation is highly controversial due to higher risk of complications, such as severe infection, antibody-mediated rejection (AMR), biliary complications, thrombotic microangiopathy, and acute kidney injury, etc. In this article, research progress in preoperative, intraoperative and postoperative strategies of ABOi liver transplantation was reviewed, aiming to provide reference for clinical application and research of ABOi liver transplantation.
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Non-infectious uveitis, an autoimmune disease that can cause severe visual impairment, can be difficult to treat. According to the prevailing hypothesis, the immune-mediated imbalance that contributes to non-infectious uveitis is primarily driven by CD4+T cells. However, recent research has shown that B cells also play a significant role in this process, participating in various ways such as antibody production, antigen presentation, and cytokine secretion in both human uveitis and experimental autoimmune uveitis models. Therapies targeting B cells have been used extensively in various autoimmune diseases. Rituximab, a B-cell inhibitor, is effective in treating noninfectious uveitis that is unresponsive to conventional corticosteroid and immunosuppressive therapy. This paper provides an overview of the involvement of B cells in non-infectious uveitis and their potential use in cellular therapies, aiming to further investigate the mechanisms and develop more effective strategies for prevention and treatment.
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We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.
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ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.
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Desde el inicio de la pandemia por COVID-19 (coronavirus disease), en el 2019, se han descrito numerosas manifestaciones clínicas de la enfermedad causada por este virus, destacando el compromiso respiratorio, hematológico, cardiovascular y neurológico. Dentro de las manifestaciones y/o complicaciones neurológicas, se encuentra la mielitis aguda transversa por COVID-19(1), cuyo diagnóstico se ha realizado principalmente clínico-imagenológico y PCR (reacción de polimerasa en cadena), o serología (+) para COVID-19, con manejos y resultados no siempre afortunados. Presentamos el caso de un paciente con mielitis aguda transversa longitudinalmente extensa en relación a COVID-19, tratada con éxito clínico con rituximab.
Since the beginning of the COVID-19 pandemic in 2019, numerous clinical manifestations of the disease caused by this virus have been described, highlighting respiratory, hematological, cardiovascular, and neurological compromise. Among the neurological manifestations and/or complications, there is acute transverse myelitis due to COVID-19(1), whose diagnosis has been made mainly clinical-imaging and PCR or serology (+) for COVID-19, with management and results not always lucky. We present the case of a patient with longitudinally extensive acute transverse myelitis in relation to COVID-19, treated with clinical success with rituximab.
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ABSTRACT Introduction: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. Method: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Results: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Conclusion: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.
Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [0,29 (0,15-0,67) >vs [0,10 (0,07-0,13); p = 0,001], [0,12 (0,05-0,22); p = 0,005] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.
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Secondary immunodeficiency can result from neoplasms, infections, or immunosuppressive therapy. Rituximab (RTX) is an anti-CD20 antibody that depletes B lymphocytes and can induce symptomatic hypogammaglobulinemia. We report 3 cases of symptomatic hypogammaglobulinemia associated with the use of RTX. In patient 1 with rheumatoid arthritis, RTX induced low levels of immunoglobulins and recurrent airway infections. RTX discontinuation led to a normalization of the humoral immune response. Patients 2 and 3, treated with RTX for non-Hodgkin lymphoma and systemic lupus erythematosus, respectively, developed persistent secondary hypogammaglobulinemia requiring immunoglobulin replacement therapy for years. After RTX discontinuation, patients may experience rapid recovery of humoral function or remain with low serum immunoglobulin levels for extended periods. With the increasing use of therapies targeting components of the immune system, a high degree of clinical suspicion for the development of secondary immunodeficiency may minimize the morbidity and mortality associated with these therapies.
As imunodeficiências secundárias podem ser uma consequência de neoplasias, infecções ou tratamentos imunossupressores. O rituximabe (RTX) é um anticorpo anti-CD20 que depleta os linfócitos B e pode induzir uma hipogamaglobulinemia sintomática. Aqui, relatamos três casos de hipogamaglobulinemia sintomática associada ao uso de RTX. Na primeira paciente com artrite reumatoide, o RTX induziu a baixos níveis de imunoglobulinas associadas a infecções de vias aéreas de repetição. Após a suspensão do RTX, houve normalização da resposta imune humoral. Os outros dois casos, com o uso de RTX para tratamento de linfoma não-Hodgkin e lúpus eritematoso sistêmico, respectivamente, as pacientes evoluíram com hipogamaglobulinemia secundária persistente, com necessidade de reposição de imunoglobulina por vários anos. Pacientes tratados com RTX podem apresentar, após a sua suspensão, uma recuperação rápida da função humoral ou permanecerem com baixos níveis séricos de imunoglobulinas por longos períodos. Com o crescente uso dos tratamentos direcionados para componentes do sistema imunológico, um alto grau de suspeição clínica para o aparecimento de imunodeficiências secundárias pode minimizar a morbimortalidade associada a estes tratamentos.
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Humanos , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.
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Resumen Antecedentes: La esclerosis múltiple es una enfermedad crónica, autoinmune y degenerativa. Las terapias blanco contra los linfocitos B han probado ser efectivas en su tratamiento; sin embargo, existen pocos estudios que evalúen su eficacia en población mexicana. Objetivo: Evaluar el impacto clínico del rituximab en pacientes con esclerosis múltiple remitente recurrente (EMRR) de reciente diagnóstico. Material y métodos: Estudio de vida real, descriptivo, en el que se evalúa rituximab como tratamiento de EMRR durante un periodo de 24 meses. Se analizaron variables clínicas pre y postratamiento; se realizó la comparación entre pacientes naïve y no naïve. Resultados: Se incluyeron 28 pacientes con EMRR. La edad media al diagnóstico fue de 30.7 años y 22 pacientes fueron naïve (78.5 %). Después de 24 meses, se observó una reducción media de 1.8 puntos en EDSS y en el número de lesiones activas por resonancia magnética. Aunque se logró establecer una diferencia significativa en ambas variables con p < 0.05, el modelo de regresión logística no mostró una relación entre las variables para alcanzar un NEDA-3. No se observaron eventos adversos graves. Conclusiones: El tratamiento con rituximab resultó en mejoría significativa clínica y radiológica en pacientes mexicanos con EMRR naïve y no-naïve.
Abstract Background: Multiple sclerosis is a chronic, autoimmune, degenerative disease. Therapies targeting B-cells have been shown to be effective in its treatment; however, there are few studies evaluating their efficacy in the Mexican population. Objective: To evaluate the clinical impact of rituximab in patients with newly-diagnosed relapsing-remitting multiple sclerosis (RRMS). Material and methods: Real life, descriptive study, in which rituximab was evaluated as treatment for RRMS over a 24-month period. Pre- and post-treatment clinical variables were analyzed; a comparison was made between treatment-naïve and non-treatment-naïve patients. Results: Twenty-eight patients with RRMS were included. Mean age at diagnosis was 30.7 years, and 22 patients were treatment-naïve (78.5 %). After 24 months, there was a mean reduction of 1.8 points in the EDSS scale and a decrease in the number of active lesions on magnetic resonance imaging; a significant difference in both variables could be established (p < 0.05). However, the logistic regression model did not show a relationship between the variables for achieving NEDA-3 criteria. No serious adverse events were observed. Conclusions: Treatment with rituximab resulted in significant clinical and radiological improvement in treatment-naïve and non-treatment-naïve Mexican patients with RRMS.
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RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.
ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.
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Azatioprina , Rituximab , Recidiva , Neuromielite ÓpticaRESUMO
Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.
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Introducción . El LES pediátrico (LESp) representa el 15% de todos los pacientes con LES. La afectación renal y neuropsiquiátrica es más agresivo en el LESp, siendo la afectación de un solo órgano la forma clínica de aparición más común. Formas de presentación como infarto cerebral y serositis son manifestaciones poco frecuentes en el LESp. El tratamiento de un LESp no difiere al de las formas adultas y el arsenal terapéutico es el mismo. El rituximab (RTX) es un agente biológico utilizado a nivel mundial en LES con excelentes resultados, sin embargo, aún no existe consenso sobre su eficacia real en LESp. Objetivos . Presentación de 2 casos de LESp con infarto cerebral y serositis como forma de presentación, que no respondieron a la terapia convencional pero sí a RTX. Métodos . Reporte de caso, con descripción del cuadro clínico, método diagnóstico y forma de tratamiento. Resultados. Primer caso: mujer de 16 años que consulta por cefalea progresiva con crisis tónico-clónica. La tomografía cerebral mostró un infarto cerebral frontoparietal izquierdo. En el examen físico se encontró livedo reticularis en miembros inferiores, dolor articular, caída del cabello y úlceras orales. Las pruebas revelaron anemia normocítica, trombocitopenia, disminución del complemento, 1/320 ANA con patrón homogéneo, 3.200 mg de proteína en muestra de orina de 24 horas y anticuerpos antifosfolipídicos negativos. Se realizó diagnóstico de LESp con compromiso renal, neurológico y hematológico, decidiendo uso de metilprednisolona 1 g EV diario durante 3 días, para luego pasar a ciclofosfamida 1 g EV mensual por 6 meses. Después de 3 meses persisten proteinuria, fatiga y artralgias. Por este motivo, se decidió utilizar rituximab a una dosis de 375 mg / m2 en días 1 y 15 cada 6 meses. Tras 4 infusiones, la proteinuria desapareció, así como las artralgias y malestar general. Actualmente mantiene scores SLEDAI-2K en remisión, con dosis bajas de prednisona. Segundo caso: niño de 10 años, presentó dolor abdominal difuso con distensión asociada de inicio más o menos abrupto. Se agregó cansancio, dificultad para respirar y palpitaciones. Una radiografía simple de abdomen no mostró niveles hidroaéreos, pero la placa torácica demostró derrame pleural bilateral con agrandamiento de la silueta cardíaca. Un ecocardiograma y una ecografía abdominal reveló derrame pericárdico y ascitis respectivamente. Al examen físico se observó palidez general, edema translúcido de miembros inferiores, roce pericárdico y disminución del soplo vesicular en ambas bases pulmonares. Las pruebas de laboratorio mostraron leucopenia, linfopenia, anemia normocítica, reactantes de fase aguda elevados, ANA 1/560, anti-ADN 280 U / mL, complemento disminuido, transaminasas elevadas, urea y creatinina normales. Se diagnosticó LESp y se pulsó con metilprednisolona 30 mg / kg / dosis durante 4 días, para luego pasar a micofenolato 600 mg / m2 diarios. Inicialmente hubo mejoría, pero después de 2 meses reapareció la serositis inicial. Se decidió usar rituximab 375 mg / m2. Después de la segunda infusión la serositis desapareció, normalizándose valores de hemograma, complemento y transaminasas. Actualmente se encuentra en remisión, con dosis bajas de prednisona. Conclusión . Los casos presentados debutaron con infarto cerebral y serositis, mostraron ANA elevados títulos y disminución del complemento. Ambos casos mejoraron con rituximab tras el fracaso a ciclofosfamida y micofenolato. Se obtuvo el consentimiento informado de los padres y los pacientes.
Introduction . Pediatric systemic lupus erythematosus (pSLE) represents 15% of all SLE patients. Renal and neuropsychiatric involvement are more aggressive in pSLE, and single organ involvement is the most commonly found clinical form. Conditions such as cerebral infarction and serositis are unusual manifestation of pSLE. Therapy for pSLE is not different from that for the adult forms, and the therapy armamentarium is the same. Rituximab (RTX) is a worldwide used biological for SLE, with excellent results; however, there is still no consensus with respect to is real efficacy in pSLE. Objectives . Presentation of two pSLE cases with cerebral infarction and serositis as main characteristics, who did not respond to conventional therapy, but who did respond to RTX. Methods . Case report, describing the clinical presentation, diagnostic methods, and therapy approach used. Results . First case: This is a sixteen-year-old girl who was brought because of progressing headache and a tonic-clonic crisis. The brain CT scan showed a left frontoparietal cerebral infarction. Physical examination revealed livedo reticularis in both legs, joint pain, hair loss, and mouth ulcers. Laboratory tests revealed normocytic anemia, thrombocytopenia, reduced complement, 1/320 ANA with a homogeneous pattern, 3.200 mg 24-hour proteinuria, and negative anti-phospholipidic antibodies. A pSLE diagnosis was made, with renal, neurologic, and hematologic involvement, so it was decided to use methylprednisolone, 1 gram IV per day for three days, and then switch to cyclophosphamide 1 g IV per month for 6 months. After three months, proteinuria, fatigue, and arthralgia persisted. For this reason, it was decided to administer rituximab, 375 mg/m2 in days 1 and 15, every six months. After four infusions, proteinuria, joint pain and malaise all disappeared. Nowadays this patient maintains SLEDAI-K scores in remission, and she is also receiving low-dose prednisone. Second case: This is a ten-year-old boy, who presented with abrupt diffuse abdominal pain associated with (abdominal) distention. Other manifestations were tiredness, shortness of breath, and palpitations. A plain abdomen X-ray film did not show hydro-aerial levels, but the chest X-ray film showed bilateral pleural effusion, and enlarged cardiac silhouette. Cardiac ultrasonography and abdominal ultrasonography revealed pericardial effusion and ascites, respectively. Findings in physical examination showed pallor translucid edema of the legs, pericardial throbbing, and reduced respiratory sounds in both pulmonary bases. Laboratory tests revealed leukopenia, lymphopenia, normocytic anemia, elevated acute phase reactants, ANA 1/560, anti-DNA 280 U/mL, reduced complement, elevated transaminases, and normal urea and creatinine. pSLE was diagnosed, and therapy instituted was methylprednisolone 30 mg/Kg/dose for 4 days, then it was switched to mycophenolate 600 mg/m2 per day. There was improvement initially, but after two months, serositis reappeared. Then it was decided to start rituximab 375 mg/m2. After the second infusion, serositis disappeared, and CBC, complement, and transaminase values returned to normal. Nowadays the patient is in remission, and he is receiving low-dose prednisone. Conclusión . Both presented cases featured cerebral infarction and serositis. They also showed high ANA titers and reduced complement. Both patients improved their condition with rituximab after failure with cyclophosphamide and mycophenolate. Informed consent from both parents and patients was obtained.
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Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.
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Adulto , Feminino , Humanos , Gravidez , Cesárea/efeitos adversos , Estado Terminal , Hidroxicloroquina/uso terapêutico , Hipestesia/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação/complicações , Neuromielite Óptica/diagnóstico , Paralisia/complicações , Complicações na Gravidez/terapia , Rituximab/uso terapêutico , Síndrome de Sjogren/complicações , Esteroides/uso terapêutico , Transtornos da VisãoRESUMO
Objective To analyze the clinical characteristics,treatment regimens and influencing factors of prognosis of patients with mantle cell lymphoma(MCL).Methods The clinical data of 41 patients with MCL was collected.These patients were initially diagnosed and treated in the Fifth Medical Center of Chinese PLA General Hospital between August 2004 and December 2019.The clinical features,therapeutic efficacy and prognosis-related factors were clarified.Results The median duration of follow-up was 68(1-165)months.The 3-year progression free survival(PFS)and overall survival(OS)were 37.29%and 62.75%respectively.Based on univariate analysis,B symptoms,Eastern Cooperative Oncology Group(ECOG)scores,the mantle cell lymphoma international prognostic index(MIPI),relapse and refractory state and the therapeutic effect were statistically significant for progression free survival.B symptoms,R-chemotherapy and therapeutic effect were statistically significant for overall survival.In multivariate analysis,B symptoms and the MIPI were statistically significant for progression free survival.B symptoms,R-chemotherapy and therapeutic effect were statistically significant for overall survival.There were statistically significant differences in 3-year OS between patients with different MIPI and MIPI-C scores.Conclusion Mantle cell lymphoma mostly occurs in elder males,and is more likely to be detected in late the stage.B symptoms,R-chemotherapy and therapeutic effect are independent prognostic factors for patients with MCL.The MIPI and MIPI-C scores have clinical guidance significance for patient survival.
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Objective:To investigate the association of rituximab-containing immunochemotherapy for non-Hodgkin lymphoma and pneumocystis pneumonia.Methods:Retrospective analysis of case data of 3 patients admitted to the Subei People's Hospital with non-Hodgkin's lymphoma complicated with pneumocystis pneumonia during immunochemotherapy containing rituximab from 2020 to 2021 and reviewed the literature.Results:Three patients developed clinical manifestations of fever, dry cough and dyspnea 8 to 21 weeks after receiving R-CHOP regimen, chest CT showed ground-glass shadows or lung balloon,and pneumocystis jirovecii infection was confirmed after bronchoscopic alveolar lavage fluid, which improved after treatment with trimethoprim-sulfamethoxazole.Conclusion:Non-Hodgkin lymphoma patients receiving immunochemotherapy containing rituximab have low immunity during chemotherapy and are more likely to be complicated by pneumocystis pneumonia and short survival with poor prognosis. Therefore,it is necessary to be aware of this situation in the process of diagnosis and treatment. Early diagnosis and treatment and reasonable prevention are the key to improve prognosis and reduce mortality.
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Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.