Posted by James
Speaker: Paul Richardson, Dana-Farber Cancer Institute, Boston, Massachusetts
Lenalidomide/Dexamethasone. The combination of lenalidomide and dexamethasone is effective for newly diagnosed MM. It demonstrated a 91% overall objective response with a complete response in 6% of the patients. An ongoing study of lenalidomide and dexamethasone (at a lower dose) is in progress to establish better tolerability than that found in the previous standard dosing study. Results to date indicate that lenalidomide/dexamethasone provides high anti-cancer responses when it is used as an initial therapy.
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Posted by James
Speaker: Thomas Shea, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Melphalan. High-dose chemotherapy appears to be commonly used to treat MM. Researchers compared the two most widely used conditioning regimens in a prospective, randomized trial before autologous stem-cell transplantation in patients with newly diagnosed symptomatic MM. The patients were younger than 65 years old. Those in arm A received 8 gray (Gy) of total-body irradiation (TBI) plus 140 mg/m2 of melphalan; those in arm B received 200 mg/m2 of melphalan (Alkeran®). A total of 282 evaluable patients were compared.
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Posted by James
Speaker: Stephanie A. Gregory, Rush University Medical Center, Chicago, Illinois
Clinical trials in patients with relapsed follicular lymphoma have shown that rituximab plus CHOP therapy (R-CHOP) is better than CHOP therapy alone. Rituximab maintenance therapy following initial FCM (fludarabine, cyclophosphamide, mitoxantrone) chemotherapy, with or without rituximab, resulted in a 94% overall response rate (P = .011). There was a trend toward improved overall survival following rituximab maintenance therapy after three years.
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Posted by James
Speaker: Thomas C. Shea, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Salvage therapy for relapse of diffuse, large B-cell lymphoma depends on the answers to several questions:
• Which relapse is it?
• Which therapies have been used in the past?
• What was the last interval of response?
• Was the prior response complete or partial?
• What are the patient’s characteristics and profile (age, organ function, medical history, and comorbidities?)
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Posted by James
Multiple Myeloma: Oncogenomics for Targeting Tumor Cells in the Microenvironment
Speaker: Kenneth Anderson, Dana-Farber Cancer Institute, Boston, Massachusetts
Recent progress in the research on multiple myeloma (MM) demonstrates the tumor-promoting influence of the micro-environment. Growth factors promote tumor cell proliferation and survival, and cytokines and chemotactic factors promote tumor cell migration and invasion. Proteases break down the basement membrane, alter the architecture of tissue structures, and promote migration and invasion by tumor cells. The vasculature of tumor cells is composed of endothelial cells that are uniquely altered in different tumors. Tumors produce growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), which recruit endothelial cells, thus affecting the growth of the tumor vasculature.
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Posted by Alex
About 10 percent of patients with myeloma will have an indolent course demonstrating only very slow progression of disease over many years. Such patients only require antitumor therapy when the serum myeloma protein level rises above 50 g/L (5 g/dL) or progressive bone lesions develop. Patients with solitary bone plasmacytomas and extramedullary plasmacytomas may be expected to enjoy prolonged disease-free survival after local radiation therapy to a dose of around 40 Gy. There is a low incidence of occult marrow involvement in patients with solitary bone plasmacytoma. Such patients are usually detected because their serum M component falls slowly or disappears initially only to return after a few months. These patients respond well to systemic chemotherapy.
The vast majority of patients with myeloma require therapeutic intervention. In general, such therapy is of two sorts: systemic chemotherapy to control the progression of myeloma, and symptomatic supportive care to prevent serious morbidity from the complications of the disease. All patients with stage II or III disease and stage I patients exhibiting Bence Jones proteinuria, progressive lytic bone lesions, vertebral compression fractures, recurrent infections, or rising serum M component should be treated with systemic combination chemotherapy. Therapy can prolong and improve the quality of life for myeloma patients.
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Posted by Alex
Multiple myeloma is a malignant proliferation of plasma cells. The tumor, its products, and the host response to it result in a number of organ dysfunctions and symptoms of bone pain or fracture, renal failure, susceptibility to infection, anemia, hypercalcemia, and occasionally clotting abnormalities, neurologic symptoms, and vascular manifestations of hyperviscosity.
Etiology The cause of myeloma is not known. Myeloma occurred with increased frequency in those exposed to the radiation of nuclear warheads in World War II after a 20-year latency. In contrast to most other B cell tumors, consistent chromosomal alterations have not been found in patients with myeloma, though cytogenetic abnormalities are noted in a substantial fraction of cases. Overexpression of myc or ras genes has been noted in some cases. Mutations in p53 and Rb-1 have also been described, but no common molecular pathogenesis has yet emerged. The murine plasmacytoma models suggest that the induction of plasmacytomas (e.g., with mineral oil injection) may require exposure to foreign antigens as well as a cellular event. Thus chronic antigenic stimulation may play a role in the transformation of a particular B cell clone. This is supported by evidence that M proteins from different persons sometimes share idiotypes. There is also some evidence for a genetic predisposition to myeloma in humans. Myeloma has been seen more commonly than expected among farmers, wood workers, leather workers, and those exposed to petroleum products. The neoplastic event in myeloma may involve cells earlier in B cell differentiation than the plasma cell. Circulating B cells bearing surface immunoglobulin that share the idiotype of the M component are present in myeloma patients. It is possible that the malignant clone escapes normal control mechanisms at a pre-plasma cell stage of differentiation and the chronic exposure to a particular antigenic stimulus drives the cell to terminal differentiation. Interleukin (IL) 6 may play a role in driving myeloma cell proliferation; a large fraction of myeloma cells exposed to IL-6 in vitro respond by proliferating. It remains difficult to distinguish benign from malignant plasma cells on the basis of morphologic criteria in all but a few cases.
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