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3.
Lancet Haematol ; 8(1): e34-e44, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357480

RESUMO

BACKGROUND: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. METHODS: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1·4 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1-3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 109 cells per L or 10 mg per day for platelets 60-100 × 109 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313). FINDINGS: Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30-0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0·0001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0·0001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events. INTERPRETATION: Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma. FUNDING: Fondazione Italiana Linfomi and Celgene.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Lenalidomida/administração & dosagem , Linfoma de Célula do Manto , Quimioterapia de Manutenção , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Lenalidomida/efeitos adversos , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Vincristina/efeitos adversos
5.
Medicine (Baltimore) ; 99(50): e23501, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327289

RESUMO

INTRODUCTION: Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma. Only 5% to 20% of patients suffering from PPL have diffuse large ß-cell lymphoma (DLBCL), and their chest computed tomography (CT) findings show single- or double-lung patchy or flocculated shadows, isolated or multifocal nodules, or masses. In this research paper, we report an older woman having multiple ground-glass nodules, who was eventually diagnosed with primary pulmonary diffuse large ß-cell lymphoma (PPDLBCL). PATIENT CONCERNS: A 69-year-old woman suffering from cough was admitted to the Second Hospital of Jilin University. DIAGNOSES: A chest CT scan showed multiple ground-glass nodules. She had received 2 weeks of antibiotic treatment, but the multiple ground-glass nodules were still present. Lung biopsy was performed by tracheoscopy, which showed non-Hodgkin diffuse large ß-cell lymphoma. INTERVENTIONS: The patient received R-CHOP-21 chemotherapy. OUTCOMES: The multiple ground-glass nodules were absorbed. CONCLUSION: The current study shows that spotting multiple ground-glass nodules in the lungs is a clear indication of the presence of PPDLBCL. It is important to spread awareness of PPDLBCL, which needs timely diagnosis and management.


Assuntos
Neoplasias Pulmonares/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tosse/etiologia , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X , Vincristina/uso terapêutico
6.
Medicine (Baltimore) ; 99(49): e23496, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285756

RESUMO

RATIONALE: Rituximab is a monoclonal antibody directed against B cells and is a first-line agent for the treatment of B cell lymphoma and a second-line agent for the treatment of idiopathic thrombocytopenic purpura (ITP). It has also been used for the treatment of several other autoimmune diseases. Epidermolysis bullosa acquisita (EBA) has never been reported as an adverse effect resulted from rituximab therapy. PATIENT CONCERNS: A 54-year-old female presented with relapse of the ITP for around eight months. She was treated with rituximab. Intramuscular chlorpheniramine and intravenous methylprednisolone and cimetidine were used as premedication before rituximab infusion. The infusion was initially started at 50 mg/h for 1 h followed by 100 mg/h till the end of infusion. The day after rituximab infusion, the patient noticed pruritic blisters on both arms and chest skin. The next day, the lesions increased in severity and extent. DIAGNOSIS: The skin biopsy established the diagnosis of EBA. H&E staining revealed subepidermal blisters infiltrated by inflammatory cells, including eosinophils and lymphocytes. Direct immunofluorescence (DIF) showed linear deposition of IgG and C3 at the dermoepidermal junction. Indirect immunofluorescence with the patient's serum on salt-split skin revealed exclusive dermal binding of circulating IgG antibasement membrane antibodies at a titer of 1:160. INTERVENTIONS: She was treated with intravenous methylprednisolone and was continued on oral prednisolone. OUTCOMES: The lesions regressed. Six weeks later, she had a recurrence of similar lesions but in milder form. This episode subsided in 4 to 5 days with topical steroid application. LESSONS: Physicians should consider this diagnosis when a patient develops bullous skin eruptions while undergoing Rituximab therapy.


Assuntos
Epidermólise Bolhosa Adquirida/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
7.
Lancet Oncol ; 21(12): e575-e588, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33271114

RESUMO

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Aprovação de Drogas , Hematínicos/uso terapêutico , Neoplasias/tratamento farmacológico , United States Food and Drug Administration , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Aprovação de Drogas/legislação & jurisprudência , Substituição de Medicamentos , Eritropoetina/análogos & derivados , Eritropoetina/uso terapêutico , Europa (Continente) , Filgrastim/uso terapêutico , Hematínicos/efeitos adversos , Humanos , Japão , Neoplasias/imunologia , Neoplasias/mortalidade , Segurança do Paciente , Formulação de Políticas , Polietilenoglicóis/uso terapêutico , Medição de Risco , Rituximab/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
8.
Hinyokika Kiyo ; 66(11): 397-401, 2020 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-33271657

RESUMO

An 84-year-old man consulted a local physician for asymptomatic macrohematuria. Abdominal ultrasonography revealed thickening ofthe bladder wall from the triangular part ofthe bladder to the posterior wall, and he was referred to our department. Cystoscopy showed extensive bladder wall thickening with edema ofthe mucosa. Abdominal contrast-enhanced computed tomography (CT) showed extensive bladder wall thickening and right external iliac lymphadenopathy accompanied by a contrast effect suspected ofbeing extravesical invasion. We performed transurethral resection ofthe bladder tumor and made the diagnosis ofmucosa associated lymphoid tissue (MALT) lymphoma. Our diagnosis made from positron emission tomography-CT performed after surgery was primary MALT lymphoma of the bladder and metastasis to the right external iliac lymph node. We administered rituximab 375 mg/m2 once a week for four times in total. CT after rituximab administration showed that the tumor and right external iliac lymph nodes had shrunk significantly, and no recurrence was present at 18 months after treatment.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias da Bexiga Urinária , Idoso de 80 Anos ou mais , Humanos , Tecido Linfoide , Masculino , Recidiva Local de Neoplasia , Rituximab
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1912-1918, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283719

RESUMO

OBJECTIVE: To analyze the efficacy of rituximab combined with CHOP/EPOCH regimen for treatment of diffuse large B-cell lymphoma(DLBCL) patients, and to explore the high risk factors of refractory and relapsed patients. METHODS: The clinical data of 72 patients with de novo DLBCL from December 2012 to December 2018 in the Department of Hematology, Zhongda Hospital Affiliated to Southeast University were retrospectively analyzed. The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH was analyzed, and survival analysis was conducted to explore the risk factors influencing refractory recurrence. RESULTS: 45 cases among 72 patients achieved complete remission (CR), 11 cases achieved partial remission (PR), the total remission rate was 77.78%. 25 cases (34.2%) refractory and relapsed. Single factor analysis showed that the B symptoms, low Hb, high NLR, low MLR, high ß2-MG, high ESR, high hs-CRP, high LDH, low ALB, low HDL were high risk factors of refractory and relapsed DLBCL. Multivariate Logistic analysis showed B symptoms, low Hb, high ß2-MG, high ESR, and high hs-CRP were significantly related with refractory relapse. Survival analysis showed that OS of refractory and relapsed group was significantly worse than that in remission group. In addition, OS of patients with B symptoms, anemia, low LMR, high ß2-MG, high hs-CRP, high LDH, low ALB and low HDL was significantly worse than that of control group. CONCLUSION: The remission rate of DLBCL patients treated by rituximab combined with CHOP/EPOCH regimen is high, but about one third of the patients still show refractory and relapsed. B Symptoms, anemia, high ß2-MG, ESR and hs-CRP are the independent prognostic factors.


Assuntos
Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1919-1922, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283720

RESUMO

OBJECTIVE: To summarize and analyze the clinical characteristics, treatment and prognosis of acute lung injury in patients with diffuse large B-cell lymphoma (DLBCL) after chemotherapy with rituximab chemotherapy, so as to improve the understanding of the disease and guide the clinical treatment. METHODS: Twenty-Six patients with DLBCL were treated with rituximab chemotherapy and developed to acute lung injury in Third Hospital of Peking University from January 2013 to September 2018 were selected. The clinical features, imaging findings, chemotherapy course, therapeutic effect and prognosis were analyzed. RESULTS: The main clinical symptoms of patients were fever, cough and chest tightness, among which 12 patients showed hypoxia and 3 patients showed respiratory failure type I. The mainly manifested chest CT was diffusive glass grinding in both lungs, and some patients were complicated with a small amount of pleural effusion. The onset chemotherapy time was mainly distributed in 2 to 4 courses, the time between the onset of symptoms and the infusion of rituximab was 8 to 49 days. 25 patients shows no obvious limitation in daily life after effective treatment, and 1 patient died of ineffective treatment. CONCLUSION: There are no typical clinical symptoms in the early stage of acute lung injury after rituximab chemotherapy in DLBCL. Early detection and early hormone therapy are very important to achieve good therapeutic effect.


Assuntos
Lesão Pulmonar Aguda , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
15.
Zhonghua Yi Xue Za Zhi ; 100(42): 3296-3302, 2020 Nov 17.
Artigo em Chinês | MEDLINE | ID: mdl-33202490

RESUMO

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
16.
Harefuah ; 159(11): 783-788, 2020 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-33210846

RESUMO

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare diseases of systemic necrotizing vasculitis affecting small and medium-sized vessels and may be associated with the presence of anti- neutrophil cytoplasmic antibody. Vessels in different organs and systems are involved, leading to various clinical manifestations of the disease. We present 3 cases of microscopic polyangiitis which have been diagnosed and treated in one medical department for over 4 years. The first patient presented with a clinical picture resembling idiopathic pulmonary fibrosis (IPF) and the diagnosis of microscopic polyangiitis (MPA) was established only when acute renal failure appeared. With appropriate therapy, the renal function normalized but her respiratory status deteriorated and she died due to pulmonary infection. The second case presented with constitutional symptoms such as general weakness, weight loss, leg edema and elevated CRP. During the investigation, mononeuritis multiplex and then MPA were diagnosed. She was successfully treated. The third patient diagnosed with MPA presented as end stage renal failure and was treated by cyclophosphamide and rituximab. He did not receive cotrimoxazole that was recommended and was hospitalized for pneumocystis jirovecii pneumonia. Despite intensive therapy in the ICU by various antibiotics and mechanical ventilation, his condition deteriorated and the patient died.


Assuntos
Falência Renal Crônica , Poliangiite Microscópica , Anticorpos Anticitoplasma de Neutrófilos , Ciclofosfamida , Feminino , Humanos , Masculino , Poliangiite Microscópica/complicações , Poliangiite Microscópica/diagnóstico , Rituximab
17.
Zhonghua Yan Ke Za Zhi ; 56(11): 839-845, 2020 Nov 11.
Artigo em Chinês | MEDLINE | ID: mdl-33152842

RESUMO

Objective: To observe the efficacy of intralesional rituximab administration in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). Methods: Retrospective case series study. The clinical and follow-up data of eight patients with POAML in the treatment group from September 2017 to December 2018 at the First Affiliated Hospital of Zhengzhou University were collected and analyzed retrospectively. The patients (3 males and 5 females) were 35 to 83 years old, with a median of 58 years. All patients received surgical treatment (most of the tumor were removed). The diagnosis of mucosa-associated lymphoid tissue lymphoma was confirmed by histopathology and immunohistochemical staining showed CD20+. Examinations such as chest CT, abdominal CT, bone marrow biopsy or positron emission tomography-CT to exclude lymphoma with systemic lesions. Patients with conjunctival POAML were injected through the subconjunctival infiltration. For the lacrimal gland POAML and the orbital POAML, the injection was performed through the periocular space by using a post-bulb syringe needle at multi-points with an interval of 1 cm, before the pressure dressing. All patients were injected 1.5 to 5.0 ml (15 to 50 mg) once every three weeks, 4 to 6 times as a treatment cycle. The injection range included or exceeded the lesion area. Then consider whether to supplement the number of treatments based on the remaining tumor. The patients' treatment doses, drug onset time, tumor regression, local reactions (local pain and swelling), systemic reaction indicators (fever, gastrointestinal reactions, complete blood count and the lymphocyte subsets), and systemic recurrence indicators (serum ß2 microglobulin and lactate dehydrogenase detecting) were recorded. Results: Two patients, including one patient with bilateral lesions, had conjunctival POAML, one patient had lacrimal gland POAML, and five patients had orbital POAML. They received 2 to 7 injections, and the total dose was 45 mg to 280 mg. There were tolerable local pain upon injections in all patients, local redness and swelling in one patient, fever in two patients, mild gastrointestinal reactions in one patient, fatigue in one patient, and palpitation and discomfort in one patient. After close observation or corresponding symptomatic treatment, the symptoms subsided. No special treatment was given. The follow-up time was 9 to 30 months, and the median was 20 months. The lymphomas in all patients were controlled without recurrence. The MRI showed that local lesions disappeared completely in five patients, and the conjunctiva and the extraocular muscle became thickened in three patients. There was no abnormity in complete blood count, serum ß2 microglobulin and lactate dehydrogenase. Conclusion: The intralesional rituximab administration is a simple, effective therapy for localized POAML with no systemic invasion. (Chin J Ophthalmol, 2020, 56: 839-845).


Assuntos
Neoplasias Oculares , Linfoma de Zona Marginal Tipo Células B , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Oculares/tratamento farmacológico , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Rituximab
18.
PLoS One ; 15(11): e0241560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151990

RESUMO

The monoclonal anti-CD20 IgG1 antibody rituximab is used as a first-line treatment for B cell lymphoma. Like all therapeutic antibodies, it is a complex protein for which both safety and efficacy heavily depend on the integrity of its three-dimensional structure. Aptamers, short oligonucleotides with a distinct fold, can be used to detect minor modifications or structural variations of a molecule or protein. To detect antibody molecules in a fold state occurring prior to protein precipitation, we generated DNA aptamers that were selected for extensively heat-treated rituximab. Using the magnetic bead-based systematic evolution of ligands by exponential enrichment (SELEX), we obtained six DNA aptamer sequences (40-mers) specific for 80°C heat-treated rituximab. In silico fold prediction and circular dichroism analysis revealed a G-quadruplex structure for one aptamer, while all others exhibited a B-DNA helix. Binding affinities ranging from 8.8-86.7 nM were determined by an enzyme-linked apta-sorbent assay (ELASA). Aptamers additionally detected structural changes in rituximab treated for 5 min at 70°C, although with lower binding activity. Notably, none of the aptamers recognized rituximab in its native state nor did they detect the antibody after it was exposed to lower temperatures or different physical stressors. Aptamers also reacted with the therapeutic antibody adalimumab incubated at 80°C suggesting similar aptamer binding motifs located on extensively heat-treated IgG1 antibodies. Within this work, we obtained the first aptamer panel, which is specific for an antibody fold state specifically present prior to protein aggregation. This study demonstrates the potential of aptamer selection for specific stress-based protein variants, which has potential impact for quality control of biopharmaceuticals.


Assuntos
Anticorpos/imunologia , Aptâmeros de Nucleotídeos/metabolismo , Temperatura Alta , Rituximab/farmacologia , Aptâmeros de Nucleotídeos/química , Dicroísmo Circular , Simulação por Computador , Humanos , Conformação de Ácido Nucleico , Técnica de Seleção de Aptâmeros
19.
Afr Health Sci ; 20(2): 871-884, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33163054

RESUMO

Background: Given the inconsistency of previous studies and the newly emerging evidence, we decided to conduct a meta-analysis. Methods: The meta-analysis included 2 randomized controlled trials and 13 observational studies 742 patients in total. Qualified studies were properly searched from databases . Data were analyzed by the RevMan 5.3 software. Results were demonstrated as WMD , SMD and RR with 95% CIs, I2 and P value. Results: we observed that a remarkable increase of complement C3 in the rituximab group than placebo group (WMDfixed= 7.67mg/dL, 95%CIs=-0.16~15.50, I2=0%, P=0.05). A significant increase of complement C4 was observed in the rituximab group than placebo group (WMDfixed=3.14mg/dL, 95%CIs=1.06~5.22, I2=0%, P=0.003). Notably decreased peripheral CD19+B cells in rituximab group than placebo group (WMDfixed=-117.93n/µl, 95%CIs=-172.94~-62.91, I2=0%, P<0.0001) in RCTs. Patients with severe or refractory SLE got more satisfactory efficacy results after receiving rituximab in observational studies, such as British Isles Lupus Assessment Group index score, SLE Disease Activity Index score, complement C3/C4, anti-dsDNA antibodies, peripheral CD19+B cells and so on. Safety profiles were no difference between rituximab and placebo groups. Conclusion: although the efficacy of rituximab is highly controversial for SLE, our study shows that rituximab presents a satisfying efficacy and safety for SLE.


Assuntos
Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Feminino , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Rituximab/efeitos adversos , Resultado do Tratamento
20.
Rev Med Suisse ; 16(715): 2218-2223, 2020 Nov 18.
Artigo em Francês | MEDLINE | ID: mdl-33206479

RESUMO

Interstitial lung disease is a frequent complication of systemic sclerosis and has now become the leading cause of death in this disorder. It mainly occurs during the first five years after the diagnosis of systemic sclerosis. Various risk factors are associated with the occurrence of interstitial lung disease, including the presence of anti-topoisomerase I antibodies (Scl-70) and the diffuse cutaneous form of systemic sclerosis. The most common radio-pathological presentation is nonspecific interstitial pneumonia, followed by usual interstitial pneumonia. The classical immunosuppressive treatment of systemic sclerosis-associated interstitial lung disease is evolving, as recent studies suggest a beneficial effect of biological agents such as rituximab and tocilizumab, and antifibrotic drugs such as nintedanib.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Imunossupressores , Pulmão , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/terapia , Rituximab/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia
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