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)

Rituximab is a chimeric monoclonal antibody directed at CD20 with significant activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). A variety of pathways of tumor cytotoxicity different from cytotoxic chemotherapy have been proposed for this therapeutic antibody including antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. This report describes that a proportion of patients with CLL receiving rituximab treatment have in vivo activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage in blood leukemia cells immediately following infusion of rituximab. This suggests that apoptosis using a pathway similar to fludarabine and other chemotherapeutic agents is intricately involved in the blood elimination of tumor cells after rituximab treatment. Patients having caspase-3 activation and PARP cleavage in vivo had a significantly lower blood leukemia cell count after treatment as compared to those without caspase activation. Significant down-modulation of the antiapoptotic proteins XIAP and Mcl-1 was also noted, possibly explaining in part how rituximab sensitizes CLL cells to the cytotoxic effect of chemotherapy in vivo. These findings suggest that the therapeutic benefit of antibody-based therapy in vivo for patients with CLL depends in part on induction of apoptosis and provides another area of focus for studying mechanisms of antibody-resistance in neoplastic cells.
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PMID:The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction. 1180 10

We report two cases with B cell malignancies (case #1: refractory mantle cell lymphoma; case #2: lymphocyte predominant Hodgkin's disease (LPHD)) who developed neutropenia post-Rituximab therapy in a setting of significant infiltration of the peripheral blood (PB) and bone marrow (BM) by T cells with an immunophenotype of large granular lymphocytes. Possible pathogenetic mechanisms are discussed.
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PMID:Evidence for T-large granular lymphocyte-mediated neutropenia in Rituximab-treated lymphoma patients: report of two cases. 1200 8

Non-Hodgkin's lymphomas (NHLs) comprise a diverse group of lymphatic malignancies of primarily B-cell origin, which are steadily increasing in prevalence worldwide. Of these, the indolent NHLs, although initially responsive to a variety of therapeutic regimens, have a continuous relapsing nature and are essentially incurable. Consequently, novel and innovative treatments are urgently required to prolong overall survival in patients with this disease. Rituximab, a human-mouse chimeric monoclonal antibody that mobilizes host effector mechanisms to destroy B cells expressing the CD20 antigen, has proven single-agent efficacy in NHL. There is a powerful rationale for combining rituximab with conventional chemotherapeutic agents to improve the outcome in NHL. A study evaluating the efficacy of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) immunochemotherapy has been conducted in 40 patients diagnosed with indolent NHL. The overall response rate was 95% (38 of 40 patients) and 22 patients (55%) experienced a complete response. No unexpected toxicity was observed with the combination therapy. Median time to progression is not reached after 50 months of follow-up. Using a highly sensitive polymerase chain reaction technique, it was also shown that rituximab plus CHOP resulted in the elimination of bcl-2-positive lymphoma cells. A further study assessing whether or not similar efficacy can be achieved using rituximab combined with fludarabine chemotherapy has provided very encouraging early results to date, with an initial overall response rate of 93% in 30 treated patients and a complete response rate of 80%. Clearance of bcl-2-positive cells, as observed in the CHOP study, has also been achieved in these patients. The combination of rituximab with conventional chemotherapeutic agents such as CHOP appears to be a viable treatment option for indolent NHL. Ongoing and planned studies will lead to the optimal use of rituximab for the treatment of NHL.
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PMID:Immunochemotherapy in indolent non-Hodgkin's lymphoma. 1204 May 29

Various clinical observations suggest that non-Hodgkin's lymphomas (NHLs), particularly those of low histologic grade, can be controlled by immunologic mechanisms. Although many effective therapies exist for the initial treatment of low grade lymphomas, none are curative and most have significant toxic side effects. Several promising lymphoma tumor antigen vaccines are being studied at medical centers throughout North America. I favor the scientific evaluation of a therapeutic strategy for follicular NHL that places immune-based therapies forward in the treatment algorithm to the initial therapeutic decision point. Active immunotherapies (therapeutic tumor vaccines) are instituted in tandem with initial cytoreductive chemotherapy, and followed by passive monoclonal antibody therapies. The tumor-specific idiotype vaccines are favored because of their demonstrated potential for clinical activity in numerous human studies and their lack of significant toxic side effects. Rituximab and other monoclonal antibodies directed at normal B-cell antigens are known to abrogate the host's ability to mount primary humoral immune responses, including antitumor antibodies evoked by tumor vaccines. Therefore, one should consider deferring the use of these agents until after an attempt at generating a host humoral antitumor response using investigational tumor vaccines. Chemotherapy regimens containing highly immunosuppressive agents (ie, fludarabine) or organ dose-limiting toxicities (ie, doxorubicin) may be best reserved for later in the disease course for those failing the more conservative approaches and for cases with adverse prognostic features. This strategy may give patients the greatest chance at prolonged remission or cure while minimizing acute and chronic toxicities, although its impact on overall survival has not been proven. Low grade NHLs remain the proving ground for this treatment philosophy. Hopefully, in the future, similar strategies may be applicable to NHLs of other grades and histologies.
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PMID:Vaccine therapies for non-Hodgkin's lymphoma. 1207 67

Humanizing xenogenic monoclonal antibodies (MAbs) by genetic engineering has greatly improved their therapeutic utility and efficacy. The chimeric CD20 MAb C2B8 (Rituximab) is a prominent representative of this new generation of therapeutic MAbs and has been proposed as a treatment of choice for recurrent follicular non-Hodgkin's lymphomas. Treatment of CD20+ B cells with MAb C2B8 triggers several cell-damaging actions including complement-mediated lysis (CDL), antibody-dependent cellular cytotoxicity (ADCC), and MAb-induced induction of apoptosis. We provide an overview of the most prominent mechanisms underlying the efficacy of antibody treatment. We introduce our concept of cross-priming of cytotoxic T-cell responses promoted by apoptosis incucing antibodies. Treatment of tumor cells with antibodies that are capable of inducing a proapoptotic signal via their cell surface target structure may not only contribute to their direct killing but also may induce cellular responses against the tumor, which may have a long-lasting protective effect. We report, using the example of C2B8 anti-CD20 treatment of lymphoma cells, that MAb C2B8-induced apoptosis of lymphoma cells not only kills these cells but also promotes uptake and cross-presentation of lymphoma cell-derived peptides by antigen-presenting dendritic cells (DC), induces maturation of DC, and allows the generation of specific CTL.
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PMID:Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? 1207 53

Rituximab, a chimeric human immunoglobulin G(1) (IgG(1)) anti-CD20 monoclonal antibody has been shown to mediate cytotoxicity in malignant B cells via several mechanisms in vitro. These include direct antiproliferative and apoptotic effects, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Glucocorticoids (GCs) are often administered in conjunction with rituximab in chemotherapeutic regimens or as premedication to reduce infusion-related symptoms. The effects of GCs on CDC and ADCC, and the direct apoptotic and antiproliferative effects of rituximab are unknown. Therefore, we evaluated these mechanisms in 9 B-cell non-Hodgkin lymphoma (B-NHL) cell lines using rituximab and GCs. Rituximab and dexamethasone induced synergistic growth inhibition in 6 B-NHL cell lines. Dexamethasone and rituximab induced significant G(1) arrest in 9 of 9 cell lines. The combination of rituximab and dexamethasone resulted in supra-additive increases in phosphatidylserine exposure and hypodiploid DNA content in 5 and 3 B-NHL cell lines, respectively. CDC and ADCC were neither impaired nor enhanced when dexamethasone and rituximab were administered concurrently. However, preincubation of both effector and tumor cells with dexamethasone reduced specific lysis in ADCC assays in 4 B-NHL cell lines. Preincubation of tumor cell lines with dexamethasone significantly increased cell sensitivity to CDC in 3 B-NHL cell lines. We conclude that the addition of dexamethasone to rituximab results in supra-additive cytotoxicity with respect to its direct antiproliferative and apoptotic effects, induces a cell-dependent increased sensitivity to rituximab-induced CDC, and has minimal negative impact on ADCC when used simultaneously with rituximab.
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PMID:Glucocorticoids and rituximab in vitro: synergistic direct antiproliferative and apoptotic effects. 1217 98

Lymphocyte-predominant Hodgkin disease (LPHD) is a unique clinical entity characterized by indolent nodal disease that tends to relapse after standard radiotherapy or chemotherapy. The malignant cells of LPHD are CD20+ and therefore rituximab may have activity with fewer late effects than standard therapy. In this phase 2 trial, 22 patients with CD20+ LPHD received 4 weekly doses of rituximab at 375 mg/m2. Ten patients had previously been treated for Hodgkin disease, while 12 patients had untreated disease. All 22 patients responded to rituximab (overall response rate, 100%) with complete response (CR) in 9 (41%), unconfirmed complete response in 1 (5%), and partial response in 12 (54%). Acute treatment-related adverse events were minimal. With a median follow-up of 13 months, 9 patients had relapsed, and estimated median freedom from progression was 10.2 months. Progressive disease was biopsied in 5 patients: 3 had recurrent LPHD, while 2 patients had transformation to large-cell non-Hodgkin lymphoma (LCL). All 3 patients with recurrent LPHD were retreated with rituximab, with a second CR seen in 1 patient and stable disease in 2. Rituximab induced prompt tumor reduction in each of 22 LPHD patients with minimal acute toxicity; however, based on the relatively short response duration seen in our trial and the concerns about transformation, rituximab should be considered investigational treatment for LPHD. Further clinical trials are warranted to determine the optimal dosing schedule of rituximab, the potential for combination treatment, and the possible relationship of rituximab treatment to the development of LCL.
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PMID:Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. 1289 84

The chimeric anti-CD20 monoclonal antibody rituximab has become part of the standard therapy for patients with non-Hodgkin's lymphoma (NHL). To date, more than 300 000 patients have been treated with rituximab worldwide, including patients with indolent and aggressive NHL, Hodgkin's disease and other B-cell malignancies. Combination of rituximab with cytotoxic agents or cytokines has been explored in a number of different studies. Rituximab is now also approved for patients with diffuse large B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone). The monoclonal antibody is generally well tolerated. Most adverse events are infusion-associated, including chills, fever and rigor related to the release of cytokines.
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PMID:An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. 1264 96

Rituximab, a monoclonal antibody directed against the B-cell specific CD20 antigen has been used with success in post-transplant lymphoproliferative disorder (PTLD) of B-cell phenotype. However, the use of such drug in children with liver transplantation and PTLD is very limited. We report a 2-yr-old liver transplant recipient with monomorphic non-Hodgkin lymphoma of B-cell origin. The lymphoma did not respond to immunosuppression withdrawal, with a subsequent allograft rejection. Despite resumption of immunosuppression and rejection treatment, the lymphoma was successfully treated with rituximab.
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PMID:Treatment of monomorphic B-cell lymphoma with rituximab after liver transplantation in a child. 1265 58

Because of high percent of failures in haematologic malignancies treatment there is a need of discovering new drugs. One of the new approaches are monoclonal antibodies, which target specific cluster differentiation antigens on tumor cells. Rituximab is an anti-CD20 antibody used in non-Hodgkin lymphoma, alemtuzumab--in B chronic lymphocytic leukaemia, gemtuzumab ozogamicin--in non-lymphoblastic leukaemia, tositumomab and ibritumomab are monoclonal antibodies binded with radiopharmaceutics and are used in non-Hodgkin lymphomas.
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PMID:["Magic bullets"--monoclonal antibodies in acute leukemia and non-Hodgkin's lymphoma treatment]. 1266


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