Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus.

Background: Rituximab, a monoclonal anti‑CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23) and pemphigus foliaceus (n = 1) treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid‑dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m2 of body‑surface area. One similar infusion was repeated after 3 months of 3rd dose. We observed the clinical outcome after 6 months of 3rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission). Observations: After follow‑up of 7‑24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Reações infusionais imediatas a agentes imunobiológicos endovenosos no tratamento de doenças autoimunes: experiência de 2.126 procedimentos em um centro de infusão não oncológico / Immediate infusional reactions to intravenous immunobiological agents for the treatment of autoimmune diseases: experience of 2126 procedures in a non-oncologic infusion centre

Introdução: Com o crescimento do uso de drogas imunobiológicas (IBD) ampliamos o conhecimento sobre sua eficácia e segurança. Objetivo: Analisar as reações infusionais imediatas (RII) às IBD endovenosas - infliximabe (IFX), rituximabe (RTX), abatacepte (ABT) e tocilizumabe (TCZ) - no tratamento de doenças autoimunes. Método: Avaliamos 2.126 infusões feitas no CID (Centro de Infusão) em 268 pacientes. A droga usada, a indicação clínica, o tempo de infusão e o uso de pré-medicação foram determinados pelo médico prescritor. Foram consideradas RII todas as intercorrências apresentadas durante a infusão e/ou período observacional de 30 minutos. A conduta adotada nas RII seguiu os protocolos do CID. Resultados: Em relação ao tipo de IBD, as infusões foram distribuídas em: IFX (1.584; 74,5%), TCZ (226; 10,63%), RTX (185; 8,7%) e ABT (131; 6,16%). As RII foram descritas em 87 procedimentos (4,09%): 77 no grupo IFX e 10 no grupo RTX. Não foram descritas RII nos grupos de ABT e TCZ. A maioria foi considerada leve (n = 5; 41,17%) ou moderada (n = 50; 58,81%) e não houve reações graves. Das infusões interrompidas, 79 (92,9%) foram reiniciadas e concluídas com êxito. Apenas seis (0,28%) não foram concluídas por causa das RII. Conclusão: Apesar da diferença entre o número de procedimentos por droga, trata-se de uma análise de "vida real", na qual a incidência de RII foi semelhante à descrita na literatura. A baixa incidência de RII corrobora os dados de segurança tanto de forma quantitativa como qualitativa e ressalta a importância do acompanhamento médico especializado durante a infusão. .

Introduction: With the increasing use of immunobiological drugs (IBD), the knowledge about their effectiveness and safety has increased. Objective: To analyze the immediate infusional reactions (IIR) to intravenous IBD: infliximab (IFX), rituximab (RTX), abatacept (ABT) and tocilizumab (TCZ) on the treatment of autoimmune diseases. Method: 2126 infusions performed in the Infusion Centre - CID in 268 patients were analyzed. The used drug, its clinical indication, infusion time, and use of premedication were determined by the prescribing physician. All intercurrences presented during infusion and/or during a thirty minutes observation period were considered as IIR. The approach adopted in IIR followed the protocols of the Infusion Centre - CID. Results: Regarding the type of IBD, the infused drugs given were: IFX (1584, 74.5%), TCZ (226, 10.63%), RTX (185, 8.7%) and ABT (131, 6,16%). IIR were described in 87 procedures (9.4%): 77 - IFX group and 10 - RTX group. IIR were not described in ABT and TCZ groups. Most were considered as mild (n = 5; 41.17%) or moderate (n = 50, 58.81%) reactions; there were no serious reactions. Regarding to discontinue infusions, 79 (92.9%) were resumed and completed successfully. Only six (0.28% of infusions) were not completed because of IIR. Conclusion: Despite the differences between the number of procedures per drug, ours is a "real life" analysis, where the incidence of IIR was similar to that described in the literature. The low incidence of IIR corroborates the safety data, both quantitatively and qualitatively, and underscores the importance of specialized medical support during infusion. .

Clinical significance of nuclear factor kappaB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy

BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-kappaB (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-kappaB or CXCR4 expression and survival was observed. CONCLUSIONS: The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.

Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult renal transplant recipients

BACKGROUND/AIMS: Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. METHODS: We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. RESULTS: There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). CONCLUSIONS: Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates.

Severe Multi-Resistant Pemphigus vulgaris: prolonged remission with a single cycle of Rituximab / Penfigo vulgar grave Multirresistente: controle prolongado com um unico ciclo de Rituximabe

Pemphigus vulgaris is an autoimmune bullous disease whose therapy is based on systemic corticosteroids, with or without immunosuppressants. Rituximab is a chimeric monoclonal antibody of the IgG class, directed at a specific CD20 B cell surface antigen, used in pemphigus vulgaris empirically since 2002, with success in 90% of the cases and long periods of remission. Male patient, 33 years old, diagnosed with pemphigus vulgaris, confirmed by histopathology and direct immunofluorescence. He was treated for seven months with numerous treatments, including immunosuppressive drugs, with an unsatisfactory response, until he had complete remission with the use of rituximab. During a 34-month follow-up period, the patient presented a slight clinical relapse, which was successfully controlled with prednisone in a daily dose of 120mg, soon reduced to 20mg.

Pênfigo Vulgar é uma doença bolhosa auto-imune, cuja terapêutica é baseada em corticoesteróides sistêmicos, associados ou não a imunossupressores. Rituximabe é um anticorpo monoclonal quimérico da classe IgG direcionado a um antígeno CD20 de superfície celular específico da célula B, usado em pênfigo vulgar desde 2002, com sucesso em 90% e longos períodos de remissão. Paciente masculino, 33 anos, diagnóstico de pênfigo vulgar, confirmado por histopatologia e imunofluorescência direta. Durante 7 meses, recebeu inúmeros tratamentos com imunossupressores, apresentando resposta insatisfatória e progressão da doença, até que logo após a introdução de rituximabe teve completa remissão. Durante um acompanhamento de 34 meses, apresentou leve recidiva clínica, controlada com prednisona 120mg/dia, rapidamente reduzida e em uso atual de Prednisona 20mg/dia.

Comparación entre CHOP-like y R-CHOP en pacientes con linfoma no Hodgkin difuso de grandes células B y folicular: 10 años de experiencia del Hospital de Clínicas de Montevideo, Uruguay / Comparison between CHOP-like and R-CHOP in diffuse large B cell and follicular lymphoma

Background: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). Aim: To analyze the benefit ofRituxi-mab in overall survival (OS) of patients with NHL. Material and Methods: Review of medical record of 230 adult patients with afirst episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. Results: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). Conclusions: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.

Linfoma marginal del bazo asociado a acidosis láctica tipo B: Caso clínico / Type B lactic acidosis associated with marginal lymphoma of the spleen: Report of one case

Lactic acidosis in the absence of hypoxia or tissue hypoperfusion (type B) is very rare and is associated with the use of some drugs or malignancy. We report a 79-year-old woman, with a marginal non-Hodgkin's lymphoma of the spleen that was subjected to a splenectomy one year ago. She presented with unexplained tachypnea associated with pancytopenia and elevation of IgM to 10 times over the higher normal limit. Laboratory tests showed the presence of metabolic acidosis and high lactic acid levels in the absence of infection, tissue hypoxia or hypoperfusion. She was treated with sodium bicarbonate and steroids without obtaining a reduction in lactate levels. Twelve days after admission, a single dose of Rituximab quickly normalized lactate concentrations and platelet count. After the fourth dose of Rituximab, pancytopenia disappeared and IgM fell to 25% of its baseline concentration.

Mucosa-associated lymphoid tissue lymphoma of the trachea: case report / Linfoma do tecido linfoide associado à mucosa de traqueia: relato de caso

CONTEXT: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid. Involvement of the trachea is extremely rare. CASE REPORT: This report describes a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented with a one-year history of coughing, dyspnea, hoarseness and weight loss. There was an infiltrative lesion in the mid-trachea. The anatomopathological diagnosis was only made from the fifth endoscopic biopsy attempt. Immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisone (R-COP) induced complete remission of the symptoms and endoscopic lesion. CONCLUSIONS: MALT lymphoma of the trachea is extremely rare and indolent disease. It has to be considered in the differential diagnosis of airway lesions. It is crucial to obtain an anatomopathological diagnosis from a specialized pathologist. Immunochemotherapy with R-COP induced complete remission of the disease.

CONTEXTO: Linfomas de tecido linfoide associado à mucosa (TLAM) são mais comumente encontrados no estômago, pulmões, órbita, glandulas salivares e tireoide. O envolvimento da traqueia é extremamente raro. RELATO DE CASO: Relato de caso raro de linfoma TLAM de traqueia, em mulher de 71 anos com tosse, dispneia, rouquidão e emagrecimento há um ano. Detectou-se lesão infiltrativa na porção média da traquéia. O diagnóstico anatomopatológico só foi obtido na biópsia do quinto procedimento endoscópico. A imunoquimioterapia R-COP (rituximabe, ciclofosfamida, vincristina e prednisona) induziu remissão completa dos sintomas e da lesão endoscópica. CONCLUSÕES: Linfoma TLAM de traqueia é uma doença indolente e extremamente rara, que deve ser considerada no diagnóstico diferencial das lesões de vias aéreas. O diagnóstico anatomopatológico por um patologista experimentado é fundamental. Imunoquimioterapia com R-COP levou à remissão completa da doença.

Primary cardiac diffuse large B-cell lymphoma with activated B-cell-like phenotype.

Primary cardiac lymphoma (PCL) is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC)-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

Pulmonary BALT Lymphoma Successfully Treated with Eight Cycles Weekly Rituximab: Report of First Case and F-18 FDG PET/CT Images

Extra marginal-zone lymphomas of the lung is a very rare tumor and it originates from bronchial-associated lymphoid tissue. A 68-yr-old woman presented with productive cough and dyspnea. A thorax computed tomography scan showed a 9 x 10 cm in size mass in the left lung and pleural effusion in the lower lobe of left lung. Positron emission tomography/computed tomography (PET/CT) revealed intense uptake foci at the upper and middle sites of left lung and slight uptake foci at the mediastinal lymph nodes which showed malignant involvement. After bronchoscopic biopsy, the diagnosis of pulmonary bronchial-associated lymphoid tissue (BALT) lymphoma was confirmed. At the end of the eight cycles weekly rituximab treatment, complete response was obtained by PET/CT findings. It is concluded that extended rituximab schedule is more effective and it would be beneficial to investigate the use of PET/CT in the diagnosis and evaluating of the treatment response of pulmonary BALT lymphoma.