Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute rejection is an expected event after transplantation and has been associated with poor long-term kidney transplant outcome. The presence of B cells in the kidney graft with acute rejection is thought to be an omnious sign, as it has been associated with poor graft outcome. There is no definitive treatment for acute rejection with B cells in the graft. Rituximab, a humanized monoclonal antibody against CD20, has been used in the treatment of B cell lymphoma. We present the case of a 49-yr-old Caucasian male with early acute kidney allograft rejection that was refractory to high doses of steroids and rabbit anti-thymocyte globulin (thymoglobulin). Repeat renal biopsy revealed T cell and B cells in the kidney graft and responded to the combination of rituximab and muromonab (a mouse monoclonal antibody to CD3 receptor). Over 9 months post-transplant, the patient remains rejection free with a serum creatinine of 1.7 mg/dL.
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PMID:Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab. 1565 47

Rituxan, a chimeric anti-CD20 antibody, is the first antibody approved for immunotherapy in non-Hodgkin's B-cell lymphoma and other B-cell lymphoproliferative disorders. Additionally, efficacy of Rituxan treatment has been reported in nonmalignant autoimmune diseases such as rheumatoid arthritis. Crosslinking of CD20 molecules by Rituxan induces therapeutic B-cell depletion. CD20 is a B-lymphocyte specific integral membrane protein, proposed to function as a store-operated calcium channel, which is activated upon receptor-stimulated calcium depletion of intracellular stores. Crosslinking of CD20 by antibodies has been reported to induce a redistribution of CD20 molecules to specialized microdomains at the plasma membrane known as lipid rafts. Here, we report that in the absence of Rituxan, CD20 exhibits a low affinity to lipid rafts. However, binding of Rituxan significantly increases the affinity of CD20 for lipid rafts resulting in its redistribution to a fraction resistant to Triton X-100 solubilization. Furthermore, we demonstrate that disturbing the raft integrity by cholesterol extraction results in dissociation of CD20 from a Triton X-100 resistant fraction followed by complete inhibition of Rituxan-induced calcium entry and apoptosis. The integrity of lipid rafts seems to play a crucial role for CD20-induced caspase activation. These data show, for the first time, that Rituxan-induced translocation of CD20 to lipid rafts is important for increased intracellular Ca(2+) levels and downstream apoptotic signalling.
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PMID:Rituxan (anti-CD20 antibody)-induced translocation of CD20 into lipid rafts is crucial for calcium influx and apoptosis. 1573 Mar 89

Rituximab (MabThera, Roche) is a chimeric monoclonal antibody directed against the CD20 antigen. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. We report the use of intralesional injections of rituximab into some but not all cutaneous lesions in a patient with multiple primary cutaneous follicular centre B-cell lymphoma. This treatment resulted in tumour regression, even of the lesions that had not been injected. We therefore hypothesize that there is systemic diffusion of rituximab from injected sites despite the low doses injected locally, or the induction of a specific antitumour immune response acting systemically.
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PMID:Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma. 1578 25

Dramatic progress in therapeutic strategy for malignant lymphoma has been made during recent few years because of the development of new drugs or new therapeutic modalities such as rituximab, purine analogue, purged autologous PBSCT or allogeneic PBSCT by the reduced intensity technique. Rituximab in particular changed the golden standard therapy for previously untreated patients with diffuse large B-cell lymphoma from CHOP therapy to rituximab-CHOP (R-CHOP) therapy in all risk groups. In follicular lymphoma with no treatment strategies associated with curative potential and median survival in the range of 8 to 13 years, prolonged progression-free survival has been reported by maintenance-use of rituximab, R-CHOP therapy, purine analog, in vivo purged auto-PBSCT by rituximab, or reduced intensity stem-cell transplantation (RIST), although no curable survival benefit has yet been demonstrated by any strategies. Short courses (4 courses) of ABVD followed by involved field irradiation therapy (IFRT) for localized early-stage Hodgkin lymphoma (HL), and full courses (6-8 courses) of ABVD (d) for advanced stage HL are the golden standard therapy for HL, respectively. Clinical trials of new therapies with more efficacy and less toxicity have been undertaken.
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PMID:[Progress in therapeutic strategy for malignant lymphoma]. 1579 14

The Groupe d'Etude des Lymphomes de l'Adulte (GELA) has conducted several phase II and III studies in patients with aggressive lymphoma, diffuse large B-cell lymphoma (DLBCL), and T-cell lymphomas during the past 20 years, in France and Belgium. These studies, have demonstrated that the outcome of patients with DLBCL may be improved and that the standard CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) regimen is not sufficient to cure a large number of patients. The first improvement was the demonstration of superiority of a dose-dense and dose-intense regimen, ACVBP (doxorubicin [Adriamycin], cyclophosphamide, vindesine, bleomycin, prednisone). The second improvement was made in young patients with poor-risk lymphoma by intensifying their treatment with high-dose therapy and autotransplant. The third and most significant improvement was in the results associated with the combination of rituximab (Rituxan) and chemotherapy. Current studies look at decreasing the. number of patients truly refractory to chemotherapy, decreasing relapse rate with rituximab maintenance, and finding an appropriate regimen for patients with T-cell lymphoma.
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PMID:Best treatment of aggressive non-Hodgkin's lymphoma: a French perspective. 1593 13

The most common subtype of aggressive non-Hodgkin's lymphoma is diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma represents a heterogeneous entity, with 5-year overall survival rates ranging from 26% to 73%. Microarray gene expression studies have confirmed that biologically distinct subgroups exist within DLBCL, and can be correlated with outcome. Initial management is usually guided by stage of disease at presentation. Approximately 25% of patients with DLBCL present with limited-stage disease and are treated with combined-modality therapy (brief chemotherapy and involved-field radiation). Most patients present with advanced-stage disease and require treatment with an extended course of chemotherapy. The CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy regimen has been the mainstay of therapy since its development in the 1970s, as more intensive chemotherapy regimens failed to show additional benefit. The era of monoclonal antibodies has transformed treatment practices for aggressive lymphoma and has led to a significant improvement in outcome. A randomized trial comparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1 monoclonal antibody, combined with CHOP chemotherapy vs CHOP chemotherapy alone for elderly patients with advanced-stage DLBCL demonstrated a significant benefitfor the combination approach. This finding has now been confirmed in two additional randomized, controlled trials and a population-based analysis, making CHOP and rituximab the standard of care for all newly diagnosed patients with DLBCL. Despite this advance, newer therapies are needed and many are under active investigation. The insights gained from molecular techniques such as gene expression profiling should permit identification of additional lymphoma-specific therapeutic targets and the development of novel agents that take into account underlying biology and allow for greater tailoring of therapy.
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PMID:Treatment of aggressive non-Hodgkin's lymphoma: a north American perspective. 1593 15

End-stage liver disease due to chronic hepatitis C virus (HCV) infection is now the most frequent indication for liver transplantation. HCV infection is associated with extrahepatic disease including cryoglobulinemia and lymphoma. The number of patients requiring liver transplantation (LT) for cirrhosis secondary to HCV infection has increased over the past 10 years; consequently, associated extrahepatic manifestations (in particular hematological malignancies) will be more commonly observed in this patient group. The management of patients with both end-stage liver disease and significant HCV-related extrahepatic disease is undefined. We report a 59-year-old man in whom extranodal marginal-zone B-cell lymphoma arising in gastric mucosa-associated lymphoid tissue (MALToma) was successfully eradicated by rituximab administration and gastrectomy at LT for HCV-related cirrhosis. Our experience with rituximab in this patient suggests that it can be used safely in the setting of severe liver disease due to HCV infection. Rituximab may be useful in preventing progression of NHL until surgical extirpation is possible.
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PMID:Liver transplantation for HCV-related cirrhosis in a patient with gastric mucosa-associated lymphoma (MALToma) pretreated with rituximab. 1597 5

A 44-year-old man was referred to our hospital with intermittent abdominal pain. Because distention of fluid- and gas-filled loops of small intestine was proved by X-ray, the patient was diagnosed as having small bowel obstruction. A laparotomy revealed a segmental stenosis in the jejunum, which showed diffuse thickening of the intestinal wall. Some mesenteric lymph nodes were swollen. Pathological examination was defined. We diagnosed diffuse large B-cell lymphoma based on the pathological findings of diffuse transmural infiltration of large lymphoid cells and flow-cytometric analyses. Rituximab was administered as adjuvant therapy at weekly doses of 375 mg/m2. Four cycles were performed every 6 mo and he remained CR. Rituximab may be effective as adjuvant therapy.
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PMID:Small bowel non-Hodgkin's lymphoma remaining in complete remission by surgical resection and adjuvant rituximab therapy. 1603 51

Rituximab, a human/mouse chimeric anti-CD20 antibody, has become part of standard therapy for patients with CD20-expressing B-cell lymphoma, and is currently under investigation for other indications including autoimmune diseases, in particular rheumatoid arthritis (RA). Its characteristic tolerability profile was established soon after clinical testing began and compares favourably with chemotherapy. The majority of patients experience mild to moderate infusion-related reactions (IRRs) during the first administration of rituximab, but the incidence decreases markedly with subsequent infusions. Current data suggest that the type of adverse events in patients with RA are similar to those in lymphoma, but that adverse events related to the rituximab infusions are less severe and less frequent. Rituximab induces a rapid depletion of normal CD20-expressing B-cells in the peripheral blood, and levels remain low or undetectable for 2-6 months before returning to pretreatment levels, generally within 12 months. Serum immunoglobulin levels remain largely stable, although a reduction in IgM has been described. T-cells are unaffected by rituximab and consequently opportunistic infections rarely occur in association with rituximab therapy. When used in combination with a variety of chemotherapeutic regimens, rituximab does not add to the toxicity of chemotherapy, with the exception of a higher rate of neutropenia. However, this does not translate into a higher infection rate. Over 540,000 patients worldwide have now received rituximab and serious adverse reactions have occurred in a small minority of patients, but for the great majority of patients, rituximab is safe and well tolerated.
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PMID:Tolerability and safety of rituximab (MabThera). 1605 60

The clinical development of immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody) has markedly affected the treatment approach for patients with B-cell non-Hodgkin's lymphoma (NHL). Rituximab was initially evaluated in relapsed indolent lymphoma and has substantial activity in this setting both alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are seeking to optimize the dose and schedule of rituximab through "maintenance" strategies exploring chemotherapy-rituximab combinations and the use of other biologic agents or antibodies that may enhance activity when employed together with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease and have potential utility as part of initial treatment as well. In diffuse large B-cell lymphoma, the addition of rituximab to CHOP chemotherapy can improve survival, though benefits are more limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled immunotherapies are ongoing in order to optimize their use for maximal clinical benefit.
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PMID:New developments in immunotherapy for non-Hodgkin's lymphoma. 1609 Nov 97


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