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)

Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at presentation, are rare events. They are frequently recognized at autopsy and generally carry a poor prognosis due either to a delay in the diagnosis or to infiltration of heart structures. We report here on two patients with large B-cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors infiltrating mainly the right atrium and the inter-atrial septum. Diagnosis was established by ultrasound-assisted transesophageal biopsy of the intra-atrial multilobated tumor mass. He was treated with Rituximab-implemented high-dose sequential (R-HDS) chemotherapy followed by autologous peripheral blood stem cell transplantation, attaining complete response. He had no evidence of disease 24 months from onset. The second patient was a 70-year-old woman who presented with pericardial tamponade and low-output cardiac failure. Despite prompt pericadiocentesis and chemotherapy with cyclophosphamide and vincristine, she died 2 weeks later. Postmortem examination revealed large B-cell lymphoma proliferation confined to the heart. Whether primitive heart localizations represent an independent prognostic factor, and what specific measures should be adopted in patients with this rare presentation is the subject of the present report and review of the literature.
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PMID:Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects. 1516 Sep 56

Purging of neoplastic cells for autologous stem cell transplantation is usually done in vivo by administering chemotherapy and/or other agents before harvesting. It is also possible to decrease malignant cells counts directly in the cell harvest. In this study, we ascertained the effect of anti-CD20 monoclonal antibody and rituximab administration on peripheral blood hematopoietic stem cells. Five samples of stem cell harvests from different patients with B cell lymphoma were obtained. Each sample was divided in two tubes with calcium gluconate (20 mEq/50 microl). Rituximab (1 mg/600,000 mononuclear cells) was added to one of the tubes. Using flow cytometry, CD19, CD20 (B cell markers), and CD95 (apoptosis marker), expression was measured at baseline and 24 h after the addition of rituximab. A one-sided t-test with equal variances was used to analyze the results. Immediately after rituximab addition, CD20 expression became null. No significant difference in variation of CD19 expression was detected after the addition of rituximab (-3.64% control vs. 0.63% rituximab, p = 0.69). Mean variations of percentage of CD95 expression were 2.9% (controls) and 10.52% (rituximab tubes) (p = 0.06). We conclude that rituximab is capable of initiating apoptosis in vitro. We found no decrease in the CD19+ cell count, used as a surrogate marker for CD20+ cells, meaning that, at least in 24 h, apoptosis activation is not capable of decreasing CD20+ cell numbers. In vitro purging of peripheral blood stem cells harvests with rituximab could be part of a broader therapeutic strategy to be offered to lymphoproliferative disorder patients.
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PMID:Induction of apoptosis and effect on CD20+ using rituximab on autologous peripheral blood stem cell harvests from patients with B cell lymphomas. 1518 35

Rituximab, a monoclonal antibody directed against the B cell-specific protein CD20, has revolutionized lymphoma treatment by providing a highly effective form of therapy with relatively mild toxic side effects. Effective as a single agent against some forms of B cell lymphoma, rituximab also has a chemosensitizing effect, enhancing the efficacy of chemotherapy against other forms of the disease. Although the mechanisms whereby rituximab achieves its effects remain incompletely understood, these seem to involve at least three distinct phenomena: (i) antibody-dependent cell-mediated cytotoxicity, (ii) complement-mediated cell lysis, and (iii) stimulation of apoptosis in target cells. The latter occurs through interaction of complexes of rituximab and CD20 in lipid rafts, with elements of a signaling pathway involving Src kinases. Effector molecules trigger various gene expression events, leading to sensitization of malignant cells to proapoptotic stimuli. Lessons learned from the research on rituximab may be applied to the rational development of antibody-based therapies against other forms of cancer.
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PMID:Empowering targeted therapy: lessons from rituximab. 1525 19

Monoclonal antibodies have been gaining a wide role in the treatment of malignant diseases. A human chimeric anti-CD20 monoclonal antibody (Mab) rituximab (Rituxan in USA; Mabthera in Europe) was approved for the treatment of refractory or relapsed low-grade or follicular non-Hodgkin's lymphoma (NHL) in 1997 (1-3). Rituximab has efficacy in other refractory CD20+ NHLs, hairy cell leukemia, plasma cell dyscrasias, posttransplant lymphoproliferative syndrome, autoimmune phenomena such as refractory hemo lytic anemias, and immune thrombocytopenias (4-8). Its combination with standard chemotherapy protocols for NHL has been investigated thoroughly owing to its synergistic effect when combined with chemotherapeutic agents (3). Coiffier et al. recently published a randomized trial showing a statistically significant survival benefit of rituximab-CHOP combination over CHOP alone in elderly patients with diffuse large-B-cell lymphoma (9,10). In addition to these widening beneficial therapeutic effects, rituximab has well-known side effects, encountered especially during its first infusion, such as chills, fever, allergic reactions, cardiopulmonary syndrome, and tumor lysis syndrome. We would like to share our clinical observation in a patient with NHL, whose disease seemed to go into an accelerated progression phase after rituximab administration.
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PMID:Rituximab-induced tumor progression: does it really happen? 1529 93

Rituximab is widely used for the treatment of B-cell non-Hodgkin's lymphoma (NHL), and encouraging results have been obtained. However, some CD20-positive NHL show minimal response to rituximab, indicating that the treatment effect depends on the presence or absence of an unidentified factor. We analyzed the relationship between the effect of rituximab plus chemotherapy and expression of Ki-67, p53 and bcl-2 and several clinical variables in cases of B-NHL, particularly follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Forty-four patients were included in the present study, and the overall treatment response rate was 68%. Twelve of 30 patients (40%) achieved a complete response, five (16%) reached an unconfirmed complete response and 13 (43%) achieved a partial response. A high serum lactate dehydrogenase level and International Prognostic Index of high or high intermediate risk were associated with a decreased response in the case of FL. Immunohistochemical assays were performed in 18 FL patients (55%) and 15 DLBCL patients (45%). Significant correlation was found between an inferior response to treatment and high Ki-67 expression in the cases of FL (P = 0.006). p53 and bcl-2 expression did not correlate significantly with the response rate. The cell cycle appears to be an important factor in the efficacy of rituximab treatment. Ki-67 expression might be a predictor of efficacy of rituximab plus chemotherapy.
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PMID:Efficacy of rituximab plus chemotherapy in follicular lymphoma depends on Ki-67 expression. 1536 34

The therapeutic unconjugated anti-CD20 Mab rituximab is used for the treatment of B-non-Hodgkin's lymphomas. We have studied the direct biological effects, signalling and gene expression profiles induced by rituximab in two human B-lymphoma cell lines, DHL4 and BJAB, using microarray, quantitative PCR and gel shift analysis. Rituximab alone inhibited thymidine uptake and induced homotypic adhesion in DHL4 only, but not BJAB. Analysis of Affymetrix microchips carrying probes for about 10,000 human cDNAs, allowed us to identify 16 genes in DHL4 and 12 in BJAB induced by rituximab at 4 h. Eleven and seven of these genes were specific for DHL4 and BJAB, respectively; whereas the remaining five were up-regulated in both cell lines. Mean induction ranged from 2- to 16-fold. Real time PCR analysis allowed us to confirm up-regulation of all genes identified, except one in BJAB. Time course of induction of eight genes was studied, showing peak induction in most cases at 4 h. The up-regulation of 5/5 genes was also observed with the F(ab')(2) fragment of rituximab. Analysis of three further B-cell lymphoma lines showed that gene induction is not restricted to BJAB and DHL4. Finally, we show that rituximab alone can induce AP1 activation in both cell lines and provide evidence that the ERK1/2 pathway is involved in the rituximab-mediated up-regulation of gene expression. These data demonstrate that rituximab alone has direct signalling capacity in different B-lymphoma lines, inducing distinct but overlapping sets of genes which may play a role in the biological and/or therapeutic effect of the antibody.
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PMID:Rituximab induces different but overlapping sets of genes in human B-lymphoma cell lines. 1544 38

In the last years monoclonal antibodies directed against B-cell associated epitopes have enriched our armentarium of therapeutic strategies against malignant B-cell lymphoma. Monoclonal antibodies are characterized by a different mode of action compared to chemotherapy, thereby opening new avenues in lymphoma treatment. These monoclonal antibodies can exert their anti-lymphoma activity directly by an intrinsic cytotoxic effect or indirectly as a carrier of cytotoxic drugs or radioisotopes. Rituximab, an anti-CD20 monoclonal antibody, was proven to be highly active in indolent as well as aggressive lymphoma, in particular when combined with chemotherapy. The anti-CD52 antibody alemtuzumab was shown to induce remissions in high risk CLL. Furthermore, clinical trials have demonstrated promising activity of monoclonal antibodies conjugated to radioisotopes such as the (131)iodine anti-CD20 antibody tositumomab or the (90)yttrium anti-CD20 antibody ibritumomab tiuxetan.
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PMID:[Monoclonal antibody treatment of malignant lymphoma]. 1551 23

Rituximab, chimeric anti-human CD20 monoclonal antibody approved for B-cell lymphoma, depletes circulating B cells. Little data exist on its use for nonmalignant diseases or B-cell subset recovery after treatment. We hypothesized that rituximab may reduce panel reactive alloantibodies (PRA) in dialysis patients awaiting renal transplantation and performed a single-dose, dose-escalation phase 1 trial. Here we report changes in lymphocyte phenotypes in subjects treated with rituximab alone. Nine subjects, 44 +/- 10 years(Yr); (5 F, 4 M) received one dose (n=3) at 50, 150, or 375 mg/m(2) without other immunosuppression. Blood was collected before dosing and intervals thereafter. No significant changes in leukocytes, total or CD3(+) lymphocytes were noted. In all, there was CD19(+) depletion by day 2(D2) (12.0 +/- 5.6 cells/mm(3) vs. 181 +/- 137, D0; p<0.01) and CD20(+) (11.0 +/- 12.0 vs. 205 +/- 116, D0; p<0.01). At 6 months (mo), CD19(+) and CD20(+) remained low (51.1 +/- 42.2, p<0.05; 75.4 +/- 38.7, p<0.05, respectively) compared to D0. CD19(+)CD5(+) cells recovered more rapidly, returning to baseline by 6mo while B memory cells (CD19(+)CD27(+)) remained low (32.3 +/- 29.0) at 1Yr (7.5 +/- 4.5; p<0.001) and 2Yr (12.1 +/- 7.9; p<0.001) after treatment. We conclude that single dose rituximab ablates B cells in high PRA dialysis patients awaiting transplantation. B-cell ablation, particularly memory B cells, was long-lasting, lagging repopulation by CD5(+) B cells.
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PMID:In vivo human B-cell subset recovery after in vivo depletion with rituximab, anti-human CD20 monoclonal antibody. 1559 85

We describe successful treatment of a 38-year-old patient with composite lymphoma stage IV(A), who presented with multifocal enlarged lymph nodes. The lymph node histology showed classic morphologic features of Hodgkin's disease, mixed cellularity subtype and follicular B-cell lymphoma. Immunophenotypic analysis showed immunoreactivity for CD20, CD10 and Ki-67 in the malignant small cell population. The areas of Hodgkin's disease demonstrated positive immunoreactivity for CD30 and CD20 in the Hodgkin's cells. Both cell populations were bcl2-oncoprotein positive. Eight courses of dose-escalated BEACOPP were administered. Restaging after chemotherapy showed radiological partial remission, but biopsy confirmed persisting follicular B-cell lymphoma without bone marrow infiltration and no evidence of Hodgkin's disease. He was treated with monoclonal CD 20-antibody (Rituximab) 10 mg/kg weekly for eight consecutive weeks due to marked positivity of CD 20-antigen in follicular lymphoma cells. This treatment was well tolerated and final staging showed complete remission of the composite lymphoma. This patient continues to be in remission 28 months after the end of the treatment. In conclusion, in the very rare case of composite lymphoma a combination of chemotherapy and subsequent immunotherapy might be considered as a promising therapeutic option.
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PMID:Sequential application of chemotherapy and monoclonal CD 20 antibody: successful treatment of advanced composite-lymphoma. 1562 15

Hematopoietic and immune function tend to deteriorate in the elderly. The incidence of hematologic diseases in the elderly is increasing as the percentage of elderly people in the whole population increases. Acute leukemia, myelodysplastic syndrome, malignant lymphoma, multiple myeloma, and myelodysplastic syndromes are commonly seen in the elderly. Malignant lymphomas are frequently seen in the elderly, and many elderly patients have poor performance status, and because they are more likely to suffer from impaired cardiac, respiratory, hepatic and renal function, as well as glucose intolerance, they are also more likely to suffer side effects due to chemotherapy. Particularly in patients aged over 80 years, to avoid side effects it is essential to adjust dosage and route of administration of chemotherapy. Although age is a significant negative prognostic factor for non-Hodgkin's lymphoma, it is possible for patients to enter complete remission with improvement of host-side factors. The clinical application of Rituximab is expected to improve chemotherapy outcomes in elderly B-cell lymphoma. The median age at the time of initial diagnosis of multiple myeloma (MM) is 60-70 years, and age is a negative prognostic factor. Clinically, higher rates of infection and heavy comorbidity are characteristic of this condition in the elderly. Although the incidence of bony lesions in elderly patients with MM is not different from the non-elderly, they do have a higher incidence of bone pain and pathologic fractures compared with the non-elderly patients. As the response to chemotherapy is good in the elderly, it is worth trying chemotherapy for MM. Polycythemia vera must be treated in the elderly, because chemotherapy decreases the incidence of thrombosis.
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PMID:[Malignant lymphoma, multiple myeloma and myeloproliferative diseases in the elderly]. 1565 67


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