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)

Despite advances in the management of aggressive non-Hodgkin's lymphoma, the treatment of relapsed and primary refractory disease remains a major challenge. High-dose chemotherapy or radio-chemotherapy followed by autologous or allogeneic stem cell transplantation (SCT) is a potentially curative treatment approach; however, the applicability of this approach is restricted to patients responding to second-line chemotherapy. Thus, second-line therapy must be both efficacious and without stem cell or organ toxicity that would compromise the ability to proceed to SCT. The ifosfamide, carboplatin and etoposide (ICE) regimen was developed to address these challenges. In a series of prospective clinical trials, 222 patients were treated with the ICE regimen. with an overall response rate of 72%. The mobilization of stem cells with this regimen was excellent,with 86% of patients mobilizing at least 2.0 x 10(6) CD34+ cells/kg. The incidence of treatment-related toxicity precluding SCT after ICE is very low. Herein, we report the clinical results of this treatment program for 222 patients with 5-year median follow-up for surviving patients. Rituximab was subsequently added to the ICE regimen for patients with diffuse large B-cell lymphoma (DLBCL) to improve upon these favorable results. This resulted in an increased complete remission rate. Additional follow-up is necessary to determine if this improvement in the complete remission rate will confer an increase in the overall survival following SCT.
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PMID:Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. 1273 24

Rituximab (chimeric anti-CD20 IgG1 monoclonal antibody) is effective in the treatment of relapsed/refractory low-grade lymphomas of B-cell origin as well as in diffuse large B-cell lymphoma. Several reports also demonstrated the efficacy of rituximab for the treatment of autoimmune cytopenia, especially for cold agglutinin disease. We report the first case, to our knowledge, of rituximab-related autoimmune hemolytic anemia. The pathophysiological mechanisms remain unknown, although the drug could act through massive cytokines liberation after destruction of CD20 positive cells by rituximab.
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PMID:Severe autoimmune hemolytic anemia following rituximab therapy in a patient with a lymphoproliferative disorder. 1280 33

Rituximab is a monoclonal antibody against the CD20 molecule which is used to treat B-cell lymphomas. In 60% of low-grade B lymphomas in which rituximab was effective at first, there was no clinical response in a second treatment and a few cases of follicular lymphomas (FL) with transformation to diffuse large B-cell lymphoma (DLBCL) have been reported. We describe a new case and hypothesize about the mechanisms of transformation: a 52-year-old man, in follow-up during 8 years for FL, who after rituximab treatment and complete remission of FL showed progressive disease involving the liver and duodenal mucosa. Immunohistochemical and molecular studies were performed on paraffin-embedded tissue samples of lymph nodes, the small intestine, and liver tumors. After rituximab treatment, biopsies of a liver lesion and the small bowel both showed CD20-negative large B-cell lymphoma. Molecular study of the initial and relapse specimens shows a CDR2 IgH rearrangement with the same height and t14;18 (MBR). The rapid relapse with the same rearrangement of IgH seems to support the interpretation that the change of grade of lymphoma and loss of CD20 expression occurred before rituximab treatment. The existence of a varying proportion of a CD20-negative cell population in every B-cell lymphoma which does not respond to rituximab should therefore be considered. The reduction of CD20 expression could be a resistance mechanism to rituximab retreatment in DLBCL as a consequence of the progression of low-grade B-cell non-Hodgkin's lymphoma (B-NHL). It is necessary to perform new biopsies to evaluate CD20 expression in relapse or the progression of B-cell lymphoma after rituximab treatment.
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PMID:CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature. 1289 84

Based on the favorable safety profile and the independent activity of rituximab in B-cell lymphoma, we evaluated its efficacy and toxicity after high-dose therapy (HDT) and autologous hematopoietic cell transplantation (HCT). Thirty-five patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients), or other (4 patients) subtypes of B-cell lymphoma received HDT followed by a purged autologous graft. The rituximab schedule was 4 weekly infusions (375 mg/m(2)) starting at day 42 after HCT and, for patients 5 to 35, a second 4-week course 6 months after HCT. All planned therapy was completed in 29 patients. With 30 months' median follow-up, the 2-year event-free survival (EFS) rate was 83% and the overall survival (OS) rate was 88%. For 21 patients with relapsed or refractory large cell lymphoma, the EFS rate was 81% and the OS rate was 85%. Grades 3 to 4 neutropenia occurred in 19 (54%) patients. A prospective study of immune reconstitution included measurements of lymphocyte subsets, immunoglobulins, and response to vaccination. Serious infections were not observed despite delayed B-cell recovery in all patients and suppressed immunoglobulin G (IgG) levels and low pneumococcus antibody titers in a subset. Rituximab after HDT and HCT is feasible, and these phase 2 data support the current US Intergroup phase 3 trial in recurrent/refractory diffuse large cell lymphoma.
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PMID:Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. 1290 46

CHOP has been the standard chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). However, indolent NHL remains largely an incurable diseases, with nearly static overall survival, and only 40% of patients with aggressive NHL are cured by CHOP. Monoclonal antibodies are an exciting advance in the treatment of lymphoma. Rituximab is a mouse/human chimeric monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal cells of the B-cell lineage, but not on primitive stem cells or mature plasma cells. Rituximab is safe and well-tolerated, and exhibit little cross-resistance with conventional chemotherapeutic agents. Clinical trials with rituximab indicate that the drug has broad application to NHL, although further clarification is needed to determine its optimal use in many of these clinical settings. In indolent NHL, rituximab has shown useful response rates, both as first-line therapy in relapsed disease. In aggressive lymphomas, diffuse large B-cell lymphoma is the most common form, the addition of rituximab to CHOP chemotherapy significantly lengthens disease-free and overall survival compared to CHOP alone as first line therapy, at least in elderly patients. These included combination with chemotherapy, prolonged or increased dosing regimens, and maintenance therapy, in which rituximab is administered to patients in remission to eliminate minimal residual disease and reduce the risk of relapse. Rituximab in vivo purging and maintenance is also being evaluated in autologous transplantation setting. Newer agents, including radiolabelled antibodies, Immunotoxin-linked antibodies and antibodies against novel target antigens are being tested in on-going clinical trial.
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PMID:[Rituximab]. 1293 62

The development of monoclonal antibodies has significantly affected the therapy of B-cell non-Hodgkin's lymphomas (NHLs). Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has activity in both indolent and aggressive B-cell lymphomas. Perhaps the greatest change has occurred in first-line therapy of advanced stage, diffuse large cell lymphoma (DLCL), where rituximab combined with conventional chemotherapy has improved both overall survival (OS) and progression-free survival (PFS) over combination chemotherapy alone. Further studies are needed assessing the role of rituximab in salvage therapy, as part of the conditioning regimen prior to autologous stem cell transplant, and as maintenance therapy for large cell lymphoma. Several novel monoclonal antibodies are in development and may also be active in DLCL. These agents may be most promising when combined with either chemotherapy or with rituximab. This review will summarize the use of rituximab in the therapy of diffuse large B-cell lymphoma and briefly describe antibodies in development.
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PMID:Antibodies for the treatment of diffuse large cell lymphoma. 1293 13

Among the monoclonal antibodies (mAbs) under clinical development, anti-CD20 mAbs have been most extensively investigated and have shown definitive clinical activities. Rituximab is a genetically engineered, chimeric anti-CD20 mAb with mouse variable and human constant regions. Consecutive clinical trials conducted in the United States, Europe, and Japan have revealed that rituximab is an effective agent, with acceptable toxicities, in the treatment of indolent and aggressive B-cell non-Hodgkin's lymphomas (B-NHLs). A recent European phase III study in elderly patients with untreated diffuse large B-cell lymphoma suggested that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy is superior to CHOP chemotherapy alone in terms of complete response rate and event-free and overall survivals. Lymphoma is inherently a radiosensitive tumor. The aim of radioimmunotherapy is to use the mAb to target radiation to lymphoma tissue while minimizing toxicity to normal cells. Clinical trials of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab showed that they have definitive efficacy in relapsed indolent B-NHL, with acceptable toxicities. A recent comparative study in relapsed indolent B-NHL showed that (90)Y-ibritumomab tiuxetan produced a higher response rate than rituximab. In addition, BL22, a recombinant anti-CD22 immunotoxin, showed significant efficacy in patients with chemotherapy-resistant hairy cell leukemia. Monoclonal antibodies will have significant roles in the treatment of lymphoid malignancies in the future.
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PMID:Rituximab and other emerging antibodies as molecular target-based therapy of lymphoma. 1295 76

Paraneoplastic pemphaigus (PNP) is a rare autoimmune mucocutaneous blistering disease that is commonly associated with underlying B-cell neoplasms. There is no standard therapy for PNP. Potent immunosuppression has been the only potentially effective treatment in the setting of malignancy because there is no correlation between tumor burden and activity of disease. Two recent case reports have noted the resolution of lesions of PNP after treatment of the underlying CD20+ B-cell lymphomas with rituximab. Rituximab is an anti-CD20 antibody that has had some success in treating proliferative B-cell disorders. We report a case of PNP in the setting of B-cell lymphoma that did not respond to this novel therapy, and discuss rituximab's putative mechanism of action along with the clinical settings in which this novel therapy may prove useful in the treatment of PNP.
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PMID:Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus. 1455 7

Rituximab has become a staple in the management of B-cell non-Hodgkin's lymphoma, but it has limited activity as a single agent, with responses in about half of patients with recurrent follicular and low-grade lymphoma. Radioimmunotherapy (RIT) may surmount inherent or acquired antibody resistance by targeting a radionuclide to tumor cells. This strategy is particularly appealing for B-cell lymphoma because CD20 affords an outstanding target and lymphomas are inherently radiosensitive. The efficacy and safety of RIT have been established in the treatment of relapsed or refractory indolent non-Hodgkin's lymphoma, and yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first RIT agent to be approved by the US Food and Drug Administration. This supplement to Seminars in Oncology seeks to present hematologists and medical oncologists with the most recent developments in RIT with (90)Y ibritumomab tiuxetan for non-Hodgkin's lymphoma, to clarify the role of the medical oncologist in the administration of the ibritumomab tiuxetan regimen, to indicate how and when RIT with (90)Y ibritumomab tiuxetan may most successfully be integrated into the continuum of treatment for patients with B-cell lymphoma, and to describe ongoing clinical trials with (90)Y ibritumomab tiuxetan in B-cell lymphomas.
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PMID:Future directions in radioimmunotherapy for B-cell lymphoma. 1471 Apr 1

Rituximab, chimeric anti-human CD-20, is approved for treatment of B-cell lymphoma in adults. It is being used experimentally in other various immune-related disease such as immune thrombocytopenic purpura, myasthenia gravis, and rheumatoid arthritis. In transplant recipients it is used for treatment of post-transplant lymphoproliferative disease, and prevention and treatment of acute rejection. There are few data on its use in children. This paper reviews the use of rituximab in these disease states and provides hypotheses for its mode of action.
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PMID:The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. 1500 36


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