Publications by authors named "Stephen M Ansell"

Yttrium 90-labeled ibritumomab tiuxetan is approved for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). To date, the efficacy of repeated courses of radioimmunoconjugate treatment in patients whose disease has progressed has not been studied as a formal endpoint in a clinical trial setting. However, several clinical studies have been conducted in patients with progressive NHL who had previously received 90Y ibritumomab tiuxetan.

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To assess the effect of rituximab therapy and other prognostic factors on overall survival in patients with post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, 30 consecutive patients diagnosed with PTLD between 1999 and 2002 were analyzed. Fifteen (50%) patients received rituximab (375 mg/m(2) once a week). Fifteen (50%) patients had other interventions including observation, immunosuppression reduction, surgery, chemotherapy, radiation or a combination of these.

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Purpose: To assess the efficacy of radiotherapy (RT) in the treatment of primary non-Hodgkin lymphoma (NHL) of the parotid gland.

Methods And Materials: Data on 35 consecutive patients seen at Mayo Clinic between 1974 and 2000 with Ann Arbor Stage I and II NHL of the parotid gland were reviewed retrospectively. Radiotherapy was given to 23 patients, and 12 patients were observed.

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BLyS, recently shown to be critical for survival of normal B cells, has been found to be elevated in a number of immune disease models. A role for BLyS in the survival of malignant B cells has also been revealed and we therefore sought to identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL). We found that tumor cells from all NHL histologic subtypes expressed one or more of 3 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expression was variable.

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Significant advances in the therapy of non-Hodgkin's lymphoma have been made with the introduction of monoclonal antibodies. The anti-CD20 antibody rituximab has become standard as monotherapy in patients with indolent lymphoma, and in combination with chemotherapy in patients with aggressive lymphoma. A number of new monoclonal antibodies targeting different molecules on lymphoma cells are now in clinical development and show promise both as single agents and in combination therapy.

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New agents with antitumor activity in neuroendocrine tumors are sorely needed. We therefore conducted a phase II study of topotecan (TOPA) 1.5 mg/m2/d for 5 days every 3 weeks in 22 patients with advanced carcinoid and islet cell tumors.

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Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting.

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Objective: To assess the clinical relevance of chemokine receptor expression on the progression of B-cell chronic lymphocytic leukemia (B-CLL).

Patients And Methods: Peripheral blood mononuclear cells from 45 patients with B-CLL were purified and compared with lymph node samples collected from 17 of these patients. Also compared were B cells obtained from peripheral blood samples from 5 healthy controls and B cells from reactive lymph nodes from 3 otherwise healthy persons.

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Objectives: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy.

Patients And Methods: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn.

Results: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma.

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Primary systemic amyloidosis (AL) is a plasma cell dyscrasia resulting in multisystem failure and death. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has been associated with higher response rates and seemingly higher overall survival than standard chemotherapy. Selection bias, however, confounds interpretation of these results.

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Interleukin-12 (IL-12) is a cytokine that facilitates cytolytic T-cell responses, enhances the lytic activity of NK cells and induces the secretion of interferon-gamma by both T and NK cells. Binding of rituximab, a chimeric murine/human monoclonal antibody, to CD20 on B-lymphocytes induces apoptosis and the Fc domain of the antibody recruits immune effector functions to mediate cell lysis. Therefore, combining IL-12 with rituximab in patients with B-cell non-Hodgkin lymphoma (NHL) may augment the immune mediated cell lysis induced by rituximab.

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Objective: To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT).

Patients And Methods: From March 1, 1999, to June 30, 2001, allogeneic and autologous hematopoietic stem cell transplantation was performed in 118 and 400 patients, respectively. We reviewed risk factors for development of posttransplantation TTP and measured vWF-CP activity during active TTP in 10 recipients.

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An important milestone in medical science is the recent completion of a "working draft" of the human genome sequence. The identification of all human genes and their regulatory regions provides the framework to expedite our understanding of the molecular basis of disease. This advance has also formed the foundation for a broad range of genomic tools that can be applied to medical science.

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Purpose: To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution.

Subjects And Methods: Sixty-six patients with biopsy-proven amyloidosis received transplants between March 1996 and January 2001. All patients had evidence of a clonal plasma cell dyscrasia; those with nonimmunoglobulin forms of amyloidosis were excluded, as were those who had no symptoms of amyloidosis, purpura, carpal tunnel syndrome, or symptomatic multiple myeloma.

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Genomics has been defined as the comprehensive study of whole sets of genes, gene products, and their interactions as opposed to the study of single genes or proteins. Microarray technology is one of many novel tools that are allowing global and high-throughput analysis of genes and gene products. In addition to an introduction on underlying principles, the current review focuses on the use of both complementary DNA and oligodeoxynucleotide microarrays in gene expression analysis.

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Purpose: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceutical, San Diego, CA) is an effective therapy for patients with relapsed B-cell non-Hodgkin's lymphoma. The predominant toxicity of 90Y ibritumomab tiuxetan has been myelosuppression, and concern has been expressed about the tolerability of further treatment after this therapy. The goal of this analysis was to evaluate the therapy given to patients who relapsed after 90Y ibritumomab tiuxetan.

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A retrospective study of 82 patients was conducted to determine the relationship of absolute lymphocyte count (ALC) recovery with clinical outcome after autologous stem cell transplantation (ASCT) in Hodgkin's disease (HD). The median overall (OS) and progression-free survival (PFS) times from the day of transplantation were significantly better for the 41 patients with ALC > or = 0.5 x 10(9) cells/l compared with the 41 patients with ALC < 0.

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In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months.

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Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by macroscopic bone marrow stromal changes that are believed to be both reactive and cytokine mediated. Furthermore, a prognostically detrimental increase in bone marrow angiogenesis has recently been demonstrated. These observations suggest a potential therapeutic role for agents that are inhibitory to angiogenesis as well as cytokines that are pathogenetically implicated in MMM.

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Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on B lymphocytes. Although binding of the Fab domain may induce apoptosis, the Fc domain recruits immune effector functions to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic T-cell responses, enhances the lytic activity of natural killer (NK) cells, and induces the secretion of interferon gamma (IFN-gamma) by both T and NK cells.

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