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)

The natural history of follicular lymphoma is to accrue large cells and become diffuse, resulting in progression/transformation to a higher-grade lymphoma. Histologic transformation occurs in approximately 60% of patients. Most often, follicular lymphomas transform into diffuse large cell lymphoma, but transformation to lymphomas classified using the Working Formulation as diffuse mixed, large cell immunoblastic, or small noncleaved cell also have been reported. Evidence of transformation may be found over time in sequential biopsy specimens, or may coexist in the same biopsy specimen. Here, we describe six cases of follicular lymphoma, large cell in five cases and mixed in one case, that transformed into a diffuse or sinusoidal CD30 antigen-positive large cell lymphoma with anaplastic cytologic features. Both the follicular and diffuse/sinusoidal components were of B-cell lineage, positive for the CD20 antigen and negative for the CD3 and CD43 antigens. The neoplastic cells expressed monotypic immunoglobulin light chain in five cases, three kappa and two lambda. BCL-2 protein was positive in four tumors, in both the follicular and diffuse/sinusoidal components in three cases, and only in the latter component in one case. Using the polymerase chain reaction (PCR), three of six cases had monoclonal immunoglobulin heavy chain gene rearrangements. The t(14;18) was not amplified in any case. Using reverse transcriptase (RT)-PCR, the t(2;5) was amplified in one of four tumors. This report highlights the heterogeneity of B-lineage anaplastic large cell lymphomas and indicates the need to consider antecedent follicular lymphoma in any B-cell lymphoma with anaplastic cytologic features.
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PMID:Transformation of follicular lymphoma into CD30-large cell lymphoma with anaplastic cytologic features. 915 76

The CD20 antigen is an attractive target for specific treatment of B-cell lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human beta-glucuronidase for the activation of the nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate to doxorubicin at the tumor site. The cDNAs encoding the light- and heavy-chain variable regions of 1H4 were cloned, joined by a synthetic sequence encoding a 15-amino acid linker and fused to human beta-glucuronidase by a synthetic sequence encoding a 6-amino acid linker. An antibody-enzyme fusion protein-producing cell line was established by transfection of the construct into human embryonic kidney 293/EBNA cells. The yield of active fusion protein was 100 ng/mL transfectoma supernatant. Antibody affinity, antibody specificity, and enzyme activity were fully retained by the fusion protein. Immunoprecipitation and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the fusion protein has a relative molecular weight (Mw) of 100 kD under denaturing conditions. Gel filtration analysis indicated that the enzymatically active form of the fusion protein is a tetramer with an Mw of approximately 400 kD. The nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate was hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human beta-glucuronidase. When the fusion protein was specifically bound to Daudi lymphoma cells, the prodrug induced similar antiproliferative effects as doxorubicin. Thus, it is feasible to construct a eukaryotic fusion protein consisting of a single-chain anti-CD20 antibody and human beta-glucuronidase for future use in the activation of anticancer prodrugs in B-cell lymphoma.
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PMID:Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human beta-glucuronidase for antibody-directed enzyme prodrug therapy. 963 15

Rituximab, a chimeric monoclonal antibody that binds specifically to the CD20 antigen, induced objective responses in 50% of patients with low-grade or follicular B-cell lymphoma. Because most nonfollicular B-cell lymphomas also express the CD20 antigen, we conducted a phase II study to evaluate the efficacy and tolerability of this new agent in patients with more aggressive types of lymphoma. Patients with diffuse large B-cell lymphoma (DLCL), mantle cell lymphoma (MCL), or other intermediate- or high-grade B-cell lymphomas according to the Working Formulation were included in this prospective randomized phase II study if they were in first or second relapse, if they were refractory to initial therapy, if they progressed after a partial response to initial therapy, or if they were elderly (age >60 years) and not previously treated. The patients received 8 weekly infusions of rituximab at the dose of 375 mg/m2 in arm A or one infusion of 375 mg/m2 followed by 7 weekly infusions of 500 mg/m2 in arm B. Patients were evaluated 2 months after the last rituximab infusion. Fifty-four patients were randomized from 9 centers in Europe and Australia (28 in arm A and 26 in arm B). A total of 5 complete responses (CR) and 12 partial responses (PR) were observed among the 54 enrolled patients, with no difference between the two doses. In an intent-to-treat analysis, the CR rate was 9% (CI95%, 3% to 20%) and the PR rate was 22% (CI95%, 12% to 36%), for an overall response rate of 31% (CI95%, 20% to 46%). An analysis of prognostic factors showed that response rates were lower in patients with refractory disease, patients with lymphoma not classified as DLCL, and patients with a tumor larger than 5 cm in diameter. DLCL and MCL patients had response rates of 37% and 33%, respectively. The median time to progression exceeded 246 days for the 17 responding patients. The most frequently reported adverse events were related to an infusion syndrome and were mild: 19% of the patients had a grade 3 related adverse event, slightly more in arm B, and only 1 patient had a grade 4 related adverse event in arm A. Two patients (3.7%) withdrew from treatment because of severe adverse events, one patient in each arm. In this first trial of rituximab in DLCL and MCL, patients experienced a significant clinical activity with a low toxicity. Rituximab has significant activity in DLCL and MCL patients and should be tested in combination with chemotherapy in such patients.
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PMID:Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. 973 Oct 49

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.
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PMID:Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases. 979 27

Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA) is the first monoclonal antibody approved by the US Food and Drug Administration for the treatment of cancer. It is a genetically engineered chimeric (murine-human) monoclonal antibody (mAb) directed against the CD20 antigen found on the surface of normal and malignant B cells. Multicenter studies have demonstrated its efficacy against relapsed low-grade and follicular non-Hodgkin's lymphoma (NHL). The mAb demonstrated tolerable side effects, primarily limited to fevers and chills associated with the first infusion. The currently recommended dosage is 375 mg/m2/infusion, given weekly for 4 weeks. Because of its human component, rituximab has low immunogenicity and should not significantly hinder future retreatment. Future studies will evaluate the antitumor activity of rituximab combined with various other chemotherapeutic or biologic agents in the treatment of B-cell lymphoma and other CD20-positive lymphoid neoplasms.
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PMID:Use of rituximab, the new FDA-approved antibody. 981 34

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a chimeric monoclonal antibody that targets mature B cells in most lymphoid B-cell malignancies. Rituximab is approved by the US Food and Drug Administration for therapy for recurrent B-cell lymphoma. In initial clinical trials the activity in small lymphocytic lymphoma, the counterpart of chronic lymphocytic leukemia (CLL), was less than 20%. In an attempt to increase the level of rituximab activity in CLL, we conducted a phase I dose-escalation study to overcome both the lower CD20 antigen density on CLL cells compared with lymphoma cells and the shorter half-life of rituximab in small lymphocytic lymphoma. Cohorts of patients were treated with escalated doses on weeks 2, 3, and 4 after an initial rituximab dose of 375 mg/m2 on day 1. The maximum dose of rituximab evaluated was 2,250 mg/m2. There is clear evidence of a dose-response relationship. Severe toxicity (grades 3 and 4) noted following the first dose of therapy in variant forms of CLL, namely mantle cell lymphoma and prolymphocytic leukemia, was uncommon in typical CLL. No unusual toxicity was noted at higher doses. Further exploration of the dosing schedule of rituximab in CLL and development of combination therapies is necessary. This agent shows promise for interaction in combined chemoimmunotherapy strategies for front-line and relapsed patients with CLL.
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PMID:High-dose rituximab therapy in chronic lymphocytic leukemia. 1122 5

CD20 antigen is expressed on nearly all human B-cells and B-lymphoma cells. Rituximab is a chimeric anti-CD20 monoclonal antibody with mouse variable and human constant regions. The toxicities of rituximab are mainly infusion-related, non-hematological grade 1 or 2 episodes. Of the 11 eligible patients enrolled in the phase I study in Japan, 2 showed CR and 5 showed PR. 90 relapsed pts were enrolled in the subsequent phase II study and treated with rituximab at 375 mg/m2 x 4 weekly infusions. The overall response rates in relapsed indolent B-cell lymphoma and mantle cell lymphoma were 61% (37/61) and 46% (6/13), respectively. Rituximab is a novel, effective anti-lymphoma agent with acceptable toxicities.
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PMID:[Treatment of B-cell lymphoma with a chimeric anti-CD20 monoclonal antibody(rituximab)]. 1180 46

Despite cutaneous B-cell lymphoma often having a relatively indolent course and low mortality, it is often resistant to conventional therapy and frequently relapses. We describe a patient with widespread cutaneous B-cell lymphoma who was treated successfully with a recently approved chimeric monoclonal antibody directed against the CD20 antigen (rituximab) and the CD20-negative relapse that resulted.
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PMID:CD20-negative relapse of cutaneous B-cell lymphoma after anti-CD20 monoclonal antibody therapy. 1186 85

CD20 antigen is expressed on nearly all human B-cells and B-lymphoma cells. Rituximab is a chimeric anti-CD20 monoclonal antibody with mouse variable and human constant regions. The toxicities of rituximab are mainly infusion-related, non-hematological grade 1 or 2 episodes. Of the 11 eligible patients enrolled in the phase I study in Japan, 2 showed CR and 5 showed PR. 90 relapsed pts were enrolled in the subsequent phase II study and treated with rituximab at 375 mg/m2 x 4 weekly infusions. The overall response rates in relapsed indolent B-cell lymphoma and mantle cell lymphoma were 61%(37/61) and 46%(6/13), respectively. Rituximab is a novel, effective anti-lymphoma agent with acceptable toxicities.
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PMID:[Rituximab, a chimeric mouse-human anti-CD20 monoclonal antibody]. 1190 60

We describe a 50-year-old female patient who developed extensive lymphomatous infiltrates on her forehead, scalp and face within a few months. Histology and immunohistochemistry of skin tumours revealed a CD20 positive follicular B-cell lymphoma. Subsequently, extracutaneous manifestations were detected by computed tomography scans and bone marrow biopsy. The patient suffered from a primary nodular malignant lymphoma with extraordinary cutaneous infiltration of the head. Therefore, combination treatment with a monoclonal antibody against the CD20 antigen, rituximab, and polychemotherapy (CHOP scheme) was administered every 3 weeks. After the second course of treatment a complete regression of cutaneous infiltrates was noticed. Follow-up biopsies on the forehead showed no evidence of CD20 positive lymphoma cells, now. Despite mild leucocytopaenia therapy was well tolerated.
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PMID:Remarkable remission of a follicular lymphoma treated with rituximab and polychemotherapy (CHOP). 1255 25


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