Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis and management of lymphoma have undergone significant changes in the past 20 years. For example, new immunophenotypic and molecular methods have replaced traditional histology-based classification schemes for lymphoma. Fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) has evolved into a potent staging tool and prognostic indicator in many kinds of lymphoma. The role of radiation therapy, especially in patients who have early-stage Hodgkin's disease, has changed substantially. The introduction of anti-CD 20 antibody therapy (Rituximab) has improved the treatment of B-cell lymphoma. These changes are linked with higher expectations for imaging, such as detection of more subtle lymphoma manifestations, evaluation of residual changes, and better assessment of early response. This article reviews clinical and radiologic features of both Hodgkin's disease and non-Hodgkin's lymphoma. It also describes the radiologic staging of lymphoma and the emerging role of FDG-PET for assessing lymphoma.
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PMID:Hodgkin's and non-Hodgkin's lymphomas. 1715 24

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.
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PMID:Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma. 1719 84

The non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of lymphoproliferative malignancies, which are most common in people aged over 55 years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL, accounting for approximately 30% of all new patients. Follicular lymphoma (FL) is the second most common NHL sub-type, and accounts for a further 22% of cases. While the incidence of most other cancers is decreasing, that of NHL is increasing steadily. During the 1970's and 1980's, worldwide NHL incidence rose by 3-4% per year. This rise has slowed in the 1990's, but an annual increase of 1-2% is still being recorded. Over the last five years, the introduction of monoclonal antibodies, and specifically the anti-CD20 monoclonal antibody, rituximab, has radically changed treatment of B-cell NHL. Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody which binds to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. This antigen is expressed on over 95% of all B cell NHLs, and on normal B cells, but not on haematopoietic stem cells, normal or malignant plasma cells. The Fc domain of rituximab recruits immune effector functions to mediate B cell lysis. Possible mechanisms of cytotoxicity include complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody-dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcgamma receptors on the surface of granulocytes, macrophages and NK cells. It is also possible that the binding of rituximab to the CD20 antigen on the cell surface may directly induce apoptosis. For patients with both follicular and diffuse large B-cell NHL, several large scale prospective randomised trials have demonstrated prolongation of remission when rituximab is incorporated into first line treatment, and, in follicular lymphoma, as a component of salvage therapy. As a result of these studies, current European indications for rituximab include: the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with cyclophosphamide, vincristine and prednisone (CVP) chemotherapy; as maintenance therapy in patients with relapsed follicular lymphoma responding to induction therapy with chemotherapy or immuno-chemotherapy; the treatment of patients with diffuse large B cell NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This paper examines the evidence supporting the use of rituximab in these settings, and places its use into the context of standard clinical practice.
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PMID:The therapeutic use of rituximab in non-Hodgkin's lymphoma. 1720 82

Patients infected with human immunodeficiency virus (HIV) are at greater risk of developing non-Hodgkin lymphoma than the general population and aggressive B-cell lymphoma has become one of the most common of the initial acquired immunodeficiency syndrome (AIDS)-defining illnesses. This review considers the prognostic factors and new approaches to the treatment of patients with AIDS-related lymphoma (ARL). As highly active antiretroviral therapy (HAART) became available, the survival of many ARL patients has become comparable to that of HIV-negative patients. This is partly due to the decrease in the incidence of opportunistic infections and improved prognosis. Both developments can also be attributed to new treatment strategies for ARL, such as the use of effective infusional regimens, Rituximab combinations and high-dose therapy with autologous stem-cell transplantation for relapsed disease. However, unresolved issues persist, such as the optimal therapy for patients with Burkitt ARL or central nervous system involvement.
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PMID:Modern management of non-Hodgkin lymphoma in HIV-infected patients. 1722 46

Rituximab is a monoclonal chimeric antibody to the CD20 antigen, which has proven to be effective in the treatment of non-Hodgkin lymphomas. Recently, rituximab has also been employed in many non-malignant autoimmune disorders (i.e., idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, connective tissue disorders and autoimmune hemolytic anemia) in which it has been used with the aim of interfering with the production of pathologic antibodies. Moreover, this agent has also shown to be effective in the treatment of acquired antibodies against factor VIII. Through a careful literature search, the current knowledge on rituximab therapy in adult acquired hemophilia A is presented in this review. Although mostly based on uncontrolled studies, the literature data suggest that this drug can be useful in the treatment of disorders of acquired inhibitors to factor VIII. However, large, prospective, randomized trials are needed to confirm these positive preliminary results.
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PMID:Rituximab in the treatment of adult acquired hemophilia A: a systematic review. 2650 21

Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective treatment for non-Hodgkin lymphomas. Moreover, rituximab has also shown efficacy in various autoimmune disorders. In this review, we will focus on the use of rituximab in childhood disorders of hemostasis associated with inhibitor formation. Although the results presented suggest that rituximab can be useful in the treatment of this subset of pediatric patients, most of the data come from isolated case reports or descriptions of small, uncontrolled series. Therefore, large, prospective, and randomized trials are needed to confirm the positive, preliminary results.
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PMID:Rituximab for the treatment of childhood chronic idiopathic thrombocytopenic purpura and hemophilia with inhibitors. 1731 49

Since rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, data regarding its benefit in terms of response rate, quality of response, progression-free survival and overall survival in B-cell lymphoid malignancies continues to expand. Rituximab has proven to be a relatively well-tolerated drug, with its major side effects being infusion related. Rituximab was approved initially by the US FDA and the European Medicines Agency for relapsed or refractory low-grade or follicular CD20+ B-cell non-Hodgkin lymphomas. Subsequently, its use has been extended to include first-line therapy in low-grade lymphoma as well as the treatment of more aggressive histological subtypes such as diffuse large B-cell lymphoma. In this article, we review the landmark trials that have impacted clinical practice in follicular and diffuse large B-cell lymphomas and the emerging data for use of rituximab as maintenance therapy in non-Hodgkin lymphoma.
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PMID:Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. 1733 47

Babesiosis is a common infection of animals and is gaining increasing attention as an emerging tick-borne zoonosis of humans in Europe. Here we report on the first case of human babesiosis in Germany in a 63-year-old splenectomised German patient with a relapse of nodular lymphocyte-predominant Hodgkin's lymphoma. After treatment with a chimeric anti-CD20 antibody preparation (Rituximab), the patient was hospitalised because of anaemia and dark urine from haemoglobinuria. Presumptive diagnosis of babesiosis was made based on piriform parasitic erythrocytic inclusions in peripheral blood smears and confirmed by Babesia-specific 18S rDNA PCR. Sequence analysis revealed a >99% homology of the amplicon with the recently described EU1 organism clustering within the Babesia divergens/Babesia odocoilei complex. Despite treatment with quinine and clindamycin the patient relapsed and developed chronic parasitaemia requiring re-treatment and long-term maintenance therapy with atovaquone before he eventually seroconverted and the parasite was cleared. Our findings suggest that human babesiosis occurs in Germany and can take a chronic course in immunocompromised individuals.
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PMID:First case of human babesiosis in Germany - Clinical presentation and molecular characterisation of the pathogen. 1735 Aug 88

Rituximab is the first anti-cancer antibody approved by the FDA for the treatment of B-cell non-Hodgkin lymphoma (B-NHL), alone or in combination with chemotherapeutic drugs. Further, rituximab is now being examined in a variety of CD20+ neoplastic diseases as well as B-cell-induced autoimmune diseases. The clinical response to rituximab is significant, resulting not only in tumor regression but also prolongation of survival. However, a subset of patients does not initially respond to rituximab or develops resistance to its further treatment. Therefore, alternative therapies for these patients are strongly desired. Rituximab activity has been thought to be by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis, and studies in model systems established the role of rituximab in cell signaling-induced perturbation of anti-apoptotic survival pathways, suggesting that the patients unresponsive to rituximab may be overcome with other CD20 antibodies with different activities. This study investigated eight novel murine antibodies directed against CD20 for their physical and biological properties in comparison with 2B8 and c2B8 (rituximab). These antibodies were derived by various antigenic and immunization procedures and selected for CD20 activity. Analysis of these antibodies revealed that they all bound to various B-cell lines and CD20-transfected CHO cells. Six of the eight antibodies shared similar variable-region amino acid sequences that were also shared by 2B8 while two monoclonal antibodies did not. Of them, 1K1791 has a distinct heavy chain and both 1K1791 and 1K1782 have distinct light chains. Not all of the antibodies inhibited cell growth and only two antibodies reacted with fixed GST-CD20 recombinant fusion protein. Noteworthy, 1K1791 was found to inhibit cell proliferation and also induced caspase-independent apoptosis in the absence of cross-linker. These findings identified new antibodies with properties and epitope specificities different from 2B8. The potential clinical application of such antibodies in the treatment of B-NHL and rituximab-resistant B-NHL is discussed.
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PMID:Characterization of novel murine anti-CD20 monoclonal antibodies and their comparison to 2B8 and c2B8 (rituximab). 1754 2

Mantle cell lymphoma (MCL) accounts for 3-10% of all non-Hodgkin's lymphomas, with median overall survival not exceeding 3-4 years. Rituximab in combination with the Hyper-CVAD regimen appears the most promising regimen; thus, we adopted it as a first-line treatment strategy in a series of 24 patients. In addition to evaluation of clinical success of the regimen, we investigated a possible role of polymorphism in IgG Fc receptors, FCgammaRIIIa and FCgammaRIIa. The frequencies of FCgammaRIIIa-158 were as follows: V/V=4/24 (17%); V/F=16/24 (66%); F/F=4/24 (17%). Those of the FCgammaRIIa-131 polymorphism were H/H=11/24 (46%), H/R=9/24 (37%), R/R=4/24 (17%). The overall response rate was 62.5%, with 33% of complete responses (CRs) after four cycles of R-Hyper-CVAD. Two-year progression-free survival (PFS) was 78% for 158V/V patients vs 75% for cases carrying phenylalanine (p=0.88). When the FCgammaRIIa polymorphism was assessed, the 2-year PFS was 82% for 131H/H patients vs 75% for those carrying arginine (p=0.26). Eighty-three percent of cases achieved Polymerase Chain Reaction (PCR)-negativity: the progression rate was significantly influenced by the minimal residual disease clearance, with 12% progression in the subgroup of PCR-negative cases versus 67% progression in PCR-positive cases (p=0.008). The achievement of PCRnegativity was not significantly influenced by FCgammaR polymorphisms. Results confirm that rituximab plus Hyper-CVAD is an effective regimen for the induction of prolonged remission in patients with aggressive MCL and suggest that rituximab efficacy is independent of the FCgammaR polymorphisms.
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PMID:The efficacy of rituximab plus Hyper-CVAD regimen in mantle cell lymphoma is independent of FCgammaRIIIa and FCgammaRIIa polymorphisms. 1759 28


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