Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melphalan was the first described treatment for patients with multiple myeloma in the 1960s and is still being used in clinical practice. However, the use of melphalan in combination with prednisone resulted in a median survival of only 2-3 years. Therefore, the dose of melphalan has been intensified since then (140-200 mg/m(2)). In order to diminish treatment-related morbidity and mortality due to severe myelosuppression induced by these regimens, high-dose melphalan is currently supported with autologous stem cells. Indications for high-dose therapy and the role of further intensification by performing second or allogeneic transplantations are discussed. Furthermore, new therapeutic modalities, such as inhibitors of angiogenesis, also showing direct antiproliferative, cytokine-related and immunomodulatory effects on plasma cells (thalidomide and its newer derivatives), inhibitors of the transcription factor NF-kappa B (proteasome inhibitors) and immunotherapy are described.
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PMID:Treatment of myeloma: recent developments. 1198 79

Patients with unexplained heart failure, hepatomegaly, nephrotic syndrome, or peripheral neuropathy should be evaluated for primary systemic (amyloid light-chain, or AL) amyloidosis by first seeking evidence of a clonal plasma cell disorder with serum and urine immunofixation studies, as well as a bone marrow biopsy. Immunostaining of the marrow biopsy for lambda and kappa isotypes will usually demonstrate a dominant clonal population of plasma cells if immunofixation studies are negative (less than 10% of cases). Tissue diagnosis of amyloidosis should be sought by biopsy of the abdominal fat or an involved organ. In addition, patients with stable myeloma or monoclonal gammopathy of undetermined significance who develop such conditions or become progressively ill should be evaluated for amyloidosis. We recommend that newly diagnosed patients with AL amyloidosis, who meet criteria for autologous hematopoietic cell transplantation, be considered for high-dose melphalan with stem cell support. Criteria usually include adequate cardiac, pulmonary, and hepatic function. AL amyloidosis patients treated with autologous transplantation frequently achieve durable complete remissions of the plasma cell disease and marked improvement in amyloid-related organ dysfunction. AL amyloidosis patients with dominant cardiac amyloid, who are without symptomatic pleural effusions and have no history of cardiac syncope or symptomatic arrhythmias, may be considered for autologous transplantation but are at increased risk of peritransplant mortality. Autologous transplantation should not routinely be offered to patients with dominant cardiac amyloid with recurrent effusions or histories of syncope or arrhythmias or to patients older than 50 years of age with more than two major organ systems involved (eg, heart, kidneys, liver, and peripheral nerves). We recommend that AL patients with isolated advanced cardiac or hepatic amyloidosis be considered for solid organ replacement followed by autologous transplantation. Otherwise, AL patients who are elderly or ineligible for autologous transplantation may be treated with oral melphalan (Alkeran, GlaxoWellcome, Middlesex, UK) and prednisone; however, because the response rate is only about 25% and the prognosis poor, such patients might also be enrolled on clinical trials of emerging therapies.
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PMID:Primary systemic amyloidosis. 1205 64

Melphalan combined with prednisone (MP) has been accepted as the standard therapy for previously untreated multiple myeloma (MM) because most studies demonstrate only a modest survival benefit of combination chemotherapy regimens when compared with MP. There have been modest gains with more intensive myeloablative regimens in combination with blood stem cell support, particularly for patients with early primary refractory disease who subsequently achieve partial remission, and for the approximately 25% to 35% of patients achieving complete remission. To preserve the ability to adequately collect stem cells, the use of alkylating agents, such as melphalan, should be limited in the previously untreated patient with myeloma (including those older than 65 years of age) who is a candidate for myeloablative therapy. Pulse dexamethasone-containing regimens provide rapid responses and may be considered the first regimens of choice. Although vincristine/doxorubicin/dexamethasone (VAD) produces responses in approximately 50% to 70% of patients with previously untreated multiple myeloma, use early in the disease has not improved survival. Outside of a specific study protocol, this regimen may be best reserved for patients with refractory (particularly relapsing) disease. Notable exceptions include patients with renal failure or plasma cell leukemia in whom the rapid responses provided by VAD may avoid potentially permanent, serious complications. Recently, new agents with novel mechanisms of action (ie, thalidomide, immunomodulatory drugs, proteosome inhibitors) have demonstrated activity in resistant myeloma. Because these agents are likely to show activity alone or in combination, newly diagnosed patients and previously untreated patients should be considered for clinical trials. Thalidomide/dexamethasone has already produced response rates of 65% to 75% in previously untreated patients. Its ease of administration along with stem cell preservation are likely to make this, followed by myeloablative therapy with stem cell support, the treatment of choice for untreated myeloma as confirmatory studies are completed.
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PMID:Newly diagnosed multiple myeloma. 1205 69

Melphalan is widely used as a preparative agent in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (SCT). Although disease relapse is the major cause of death after a melphalan-conditioned autograft, the mechanism remains unclear. Melphalan produces a number of DNA adducts with the DNA interstrand crosslink (ICL) considered to be the critical cytotoxic lesion. By using a modification of the single-cell gel electrophoresis (Comet) assay, we have measured formation and repair of DNA ICL in plasma cells from melphalan- naive and melphalan-treated patients (ie, those who have relapsed after a melphalan-conditioned autologous SCT or oral melphalan therapy). Similar levels of dose-dependent DNA interstand crosslinking were observed in cells from both melphalan-naive and -treated patients. However, marked differences in ICL repair were observed: cells from naive patients showed no repair, whereas those from treated patients exhibited between 42% and 100% repair at 40 hours. In vitro sensitivity to melphalan in plasma cells was found to correlate with ICL repair. These findings suggest that ICL repair may be an important mechanism by which melphalan resistance emerges after autologous SCT or oral therapy. This mechanism may have implications for MM patients undergoing melphalan therapy.
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PMID:Repair of DNA interstrand crosslinks as a mechanism of clinical resistance to melphalan in multiple myeloma. 1207 31

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells typically occurring in elderly patients. The clinical manifestations of this disease result primarily from the accumulation of monoclonal protein (paraprotein) in the serum and/or urine, anemia, lytic bone lesions, hypercalcemia, renal insufficiency, and immune deficiency. Multiple myeloma is incurable with standard chemotherapy. Melphalan and prednisone has been the mainstay of treatment for MM for about three decades. This regimen results in a clinical response in approximately 60% of patients and a median survival of approximately 36 months. A variety of combination therapies have also been used in MM, but have not been considered to offer a significant benefit compared with standard therapy. In early trials, bendamustine monotherapy was as effective as cyclophosphamide and various combination therapies in achieving remission in MM. This article describes a prospective, randomized, phase III study designed to compare the efficacy of bendamustine/prednisolone with a standard melphalan/prednisolone regimen.
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PMID:Bendamustine in the treatment of multiple myeloma: results and future perspectives. 1217 Apr 29

The treatment of multiple myeloma still remains under investigation. Conventional chemotherapy with currently used agents (i.e., Melphalan) effects complete remission in no more than 5% of patients. High dose chemotherapy followed by hematopoietic stem cells transplantation results in complete remission rates between 25% and 75% and a 3-year probability of event-free survival between 40% and 60% but is not curative since most patients relapse after 1.5 to 3 years. Therefore, it becomes the treatment of choice for multiple myeloma. The drugs used in high dose therapy include: high dose melphalan (200 mg/m2) as single agent., melphalan (140 mg/m2) and total body irradiation (TBI), Busulfan and melphalan... etc. The use of the peripheral blood stem cell transplantation has allowed a reduction in the toxicity of high-dose regimens, but has not led to an increase in the overall response rate or survival. Hematopoietic stem cells from peripheral blood are preferred for transplantation because they restore hematopoiesis more rapidly than do bone marrow cells and the numbers of tumor cells are lower in peripheral blood than bone marrow cells. Peripheral blood stem cell transplantation was associated with significant reduction in the duration of aplasia and transfusion requirements. Several regimens have been proposed for stem cells mobilization including: High-dose cyclophosphamide and G or GM-CSF, G-CSF alone, and cyclophosphamide and etoposide with G-CSF... ect.. Further attempts to improve the results of autotransplantation have included intensification with tandem transplantations (double transplants) and reduction of tumor cells in stem cell infusion. The aim of this review is to summarize the current knowledge about the treatment of multiple myeloma with high dose chemotherapy with autologous hematopoietic stem cell transplantation.
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PMID:High intensity regimens with autologous hematopoietic stem cell transplantation as treatment of multiple myeloma. 1241 71

Twenty-one patients with relapsed and refractory Durie-Salmon stage III multiple myeloma who had either failed at least three previous regimens or presented with poor performance status, neutropenia, or thrombocytopenia were treated with up to four cycles of combination melphalan (50 mg intravenously), thalidomide (titrated to target of 400 mg orally daily), and dexamethasone (40 mg/day orally on d 1 to 4) every 4-6 wk. Maintenance treatment consisting of daily thalidomide and monthly dexamethasone was continued until disease progression. Although generally tolerated, combination melphalan/thalidomide/dexamethasone produced grade 4 neutropenia and thrombocytopenia in 52% and 38% of patients, respectively. Grade 3 nonhematologic toxicities included fatigue (14% of patients), neuropathy/paresthesia (5%), and nausea (5%). Four patients died while on therapy: two from neutropenic complications and two from progressive disease. Melphalan/ thalidomide/dexamethasone was highly active in this poor prognosis population: Serum monoclonal protein reductions > or = 25% occurred in 14 (70%) of 20 evaluable patients, including 1 patient with a complete response and 2 (13%) patients with reductions of 96%. Median progression-free-survival was 270 d (range: 73 to > 787 d) and median overall survival was 382 d. Median progression-free survival (> 420 d) has not been reached among patients responding to melphalan/thalidomide/dexamethasone. These results show that melphalan/thalidomide/dexamethasone therapy is active and generally tolerated in heavily pretreated multiple myeloma patients whose prognosis is otherwise poor.
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PMID:Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma. 1251 15

Gelatinous transformation of the marrow (GTBM) has been associated with various conditions. We present a unique case of GTBM in a patient with myeloma following treatment with Melphalan.
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PMID:Gelatinous transformation of bone marrow following chemotherapy for myeloma. 1256 97

Optimal methods of stem cell mobilization in multiple myeloma are undefined, and contaminating clonotypic cells could contribute to disease recurrence. A phase 2 trial of intravenous melphalan (60 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg/d) for mobilization was performed. To enhance reliability, contamination was assessed with 2 sensitive methods, immunoglobulin light and heavy chain variable region patient-specific limiting-dilution polymerase chain reaction (PCR). We evaluated 29 stem cell components (SCCs) from 15 patients; for 9 SCCs, only VL PCR was used because of light chain disease or technical problems with VH primers. For 20 SCCs, VL and VH PCR results were highly correlated (r2 = 0.93, P <.01), with 35% (7 of 20) having identical estimates. VH PCR gave significantly higher estimates for 8-and VL PCR for 5-SCCs, supporting the utility of using 2 methods. Estimated clonotypic contamination per SCC was 0.0009% (range, 0%-0.1%) or 0.5 x 10(4) clonotypic cells per kilogram (range, 0-41.2 x 10(4)/kg), and contamination correlated with CD34+ cells collected (r2 = 0.42, P <.01). Melphalan-mobilized SCCs contain minimal clonotypic contamination.
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PMID:Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination. 1264 34

Mini-transplantations in leukemia or MDS in the elder patients are reported to have almost the same results as of the young patients. On the other hand, multiple myeloma is considered that no conventional chemotherapy is curable. Here are some reports of short term of observations at our hospital. We tried pre-conditioning with ATG(2.5/kg x 2), TBI(1 Gy x 2), L-PAM (70 mg x 2), M-Pred(700 mg/m2 x 5) to ten progressive multiple myeloma cases, 40% became mixed chimera and they all became completely donor type with DLI. In almost 4 years of observations, over all survival rate is 68% that it is worth while to continue this treatment.
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PMID:[Multiple myeloma]. 1451 28


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