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 (Alkeran) is an alkylating agent commonly used in the treatment of multiple myeloma and other neoplasia. We have isolated melphalan-resistant (MelR) Chinese hamster ovary cells in vitro. Stably resistant clones were observed with a frequency of about 10(-7) after a single drug exposure. Two clones, MelR1 and MelR6, were studied in detail, and their phenotypes were compared to a colchicine-resistant membrane permeability mutant (CHRC5) isolated previously by Ling and Thompson (J. Cell Physiol., 83: 103-116, 1974), which was cross-resistant to melphalan. The MelR cones were cross-resistant to the nitrogen mustard class of alkylating agents, such as melphalan, nitrogen mustard, and chlorambucil, but not to alkylating agents, such as methanesulfonic acid:ethyl ester or mitomycin C. The MelR clones differed from CHRC5 in their lack of cross-resistance to puromycin and Adriamycin. Studies with [14C]melphalan showed CHRC5, but not the MelR clones, to be defective in drug accumulation into whole cells. The mechanism of melphalan resistance in CHRC5 is attributed to reduced drug accumulation due to a plasma membrane alteration. In the MelR clones, investigation of drug distribution into cell subfractions revealed reduced accumulation into the nucleus compared to the parental cell line. We therefore propose that the mechanism of resistance in the MelR cells results from a nuclear alteration(s) specific to a subclass of alkylating agents.
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PMID:Selection and characterization of Chinese hamster ovary cell mutants resistant to melphalan (L-phenylalanine mustard). 744 83

Melphalan and prednisone are still considered the "gold standard" in the treatment of multiple myeloma. In the submitted paper the authors review randomized studies which evaluate the contribution of polychemotherapy in this disease. Polychemotherapy induces a major number of therapeutic responses and its onset is more rapid. However, as regards the survival period the groups treated by standard therapy and polychemotherapy do not differ significantly.
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PMID:[Initial treatment of multiple myeloma]. 831 Jun 71

Three patients suffering from IgD myeloma, which a rare variant of multiple myeloma which often has an aggressive course, were studied retrospectively in order to elucidate the existence of clinical or laboratory features in relationship to survival time. The patients were monitored in follow-up for a time variable for 8 to 52 months. All patients received courses of chemotherapy using an association of Melphalan and Prednisone (MP); one patient also received recombinant interferon alpha in association. Response to chemotherapy, with a > 50% reduction of serum M component, disappearance of Bence Jones proteinuria and permanent control of the disease was achieved in all patients. The median duration of survival in IgD myeloma is shorter than that currently observed in patients with other myeloma types: in our series one patient died 8 months after diagnosis but other two patients are still alive 8 and 52 months after diagnosis, respectively. Great difficulty was encountered in analysis of unfavourable prognostic clinical and laboratory data: in our series, in spite of the small number of cases, the Authors observe that only the relief of increased serum levels of Lactate Dehydrogenase (LDH) seem to be in relationship with a trend of shorter survival. The authors, confirming the particular clinical and laboratory aspects of this myeloma, stress that there may coexist cases in which standard chemotherapy failed to control the diseases: these seem to indicate neoplasia with fast growth kinetics. Further studies are necessary in order to identify new prognostic index which allows the identification of selected groups of patients who can profit from a combination chemotherapy regimen other than the standard MP association.
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PMID:IgD multiple myeloma. A report of three cases. 866 86

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to three years. In the following three decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought contraverse results. The latest metaanalysis and data published by Ludwig support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trend are reviewed in this paper.
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PMID:[Treatment of multiple myeloma--melphalan monotherapy after bone marrow transplantation]. 869 16

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to 3 years. In the following 3 decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than after monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought controversial results. The latest metaanalysis and data published support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trends are viewed in this paper.
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PMID:Evolution of multiple myeloma treatment from melphalan monotherapy to bone marrow transplantation. 879 81

The purpose of this study was to evaluate a new regimen for the treatment of multiple myeloma based on alternating 3-week cycles of chemotherapy and interferon (rIFN alpha 2). In this prospective phase II clinical trial the Eastern Cooperative Oncology Group evaluated a regimen consisting of 2 cycles of VBMCP (Vincristine 1.2 mg/M(2) IV d1, BCNU 20 mg/M(2) IV d1, Melphalan 8 mg/M(2) PO dl-4, Cyclophosphamide 400 mg/M2 IV d1, Prednisone 40 mg/M(2) PO d1-7) followed by alternating 3-week cycles of VBMCP and rIFN alpha2 5 Mu/M(2) SC 3x/week. Treatment was administered for 2 years. Fifty-eight patients with previously untreated multiple myeloma were entered. Objective response (OR) required 50% decrease in M-protein with correction of severe anemia and no progression of skeletal disease. Complete remission (CR) was defined by disappearance of M-protein and normalization of the bone marrow morphology. Life table analysis was utilized to express survival and response duration. Fifty-four patients were evaluable. Objective response was seen in 80% of patients including CR in 30% (16 patients). The median response duration is 35 months, 46 months for patients with CR. The median survival is 42 months for all patients. Five year survival is 42%. Although 78% of patients had neutrophil nadirs <1000 x 10(9)/L, the incidence of severe infection was only 9%. These data demonstrate that VBMCP + interferon is an effective new regimen combining chemotherapy with a biological response modifier for the treatment of multiple myeloma. The incidence of CR is high, and the response and survival durations appear to be 1 year longer than usually seen with standard chemotherapy. A current ECOG randomized trial compares VBMCP + interferon with VBMCP alone.
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PMID:Complete remission induction with combined VBMCP chemotherapy and interferon (rIFN alpha 2b) in patients with multiple myeloma. 883 1

Results of studies using IFN-alpha treatment for maintaining remission and prolonging survival in multiple myeloma (MM) are in conflict and trials seeking optimum use for this biological response modifier are continuing. Between 1989 and 1993 a prospective randomized multicentre trial was undertaken to evaluate the role of the combination of IFN-alpha with chemotherapy (CT) in maintenance treatment of MM. For remission induction, in patients 65 yr or younger, we used VAD (group A) and for the remaining Melphalan and Prednisone (MP) (group B). For maintenance, patients were randomized to receive IFN-alpha 3 x 10(6) i.u. s.c. t.i.w. (group I) or alternating monthly cycles of IFN-alpha and CT. The CT cycles were also alternated (VAD, MP, CP) in an effort to prevent the development of multidrug resistance. Median survival of the two maintenance groups from randomization (36 months for group I and 31 months for group II, p = 0.3) as well as response duration (13 months in group I and 15 months in group II, p = 0.95) were similar. Toxicities were more pronounced both with VAD induction and in the combination maintenance arm. The addition of chemotherapy to the IFN maintenance regimen in MM did not have an advantage over IFN alone.
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PMID:Maintenance therapy with interferon-alpha (IFN-alpha) versus IFN-alpha plus chemotherapy in multiple myeloma (MM). The Greek Myeloma Study Group. 885 91

The diagnosis of multiple myeloma (MM) is often difficult; most patients present with asymptomatic gammopathy. The only findings that confirm a diagnosis of MM are an elevation in the M-component or extension of the lytic bone lesions that are the hallmark of the disease. Tests that delineate plasma cell biology, such as plasma cell proliferation rate, are helpful; magnetic resonance imaging can disclose bone marrow lesions leading to subsequent osteolytic disease. After the diagnosis of MM has been established and prognostic factors identified, the appropriate therapy can be determined. Melphalan and prednisone are no longer considered to be the "gold standard" of therapy. In fact, this approach is suitable for less than half of patients with myeloma. This article presents guidelines for standard treatment options and examines the efficacy of new high-dose chemotherapy approaches.
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PMID:Diagnosis, prognosis, and standard treatment of multiple myeloma. 908 Dec 7

Melphalan and prednisolone (MP) have been the standard therapy for multiple myeloma for more than 25 years. Although they produce an objective response in 50-60% of patients, complete remission (CR) is rare and the median survival period is generally 24 to 30 months. Many combination chemotherapeutic agents have been used and resulted in approximately 70% objective response, but the median duration of survival has not significantly been improved. VAD regimen is effective for many patients with myeloma resistant to MP therapy. Furthermore, VAD-cyclosporin combination induces responses in approximately 40% of patients with VAD-resistant myeloma, with increased expression of the multi-drug resistant gene (MDR). Intravenous administration of high dose-melphalan also produces responses in approximately 30% of patients with myeloma resistant to VAD. Interferon-alpha therapy with an alkylating agent-glucocorticoid regimen, shows a higher response rate but similar survival time, compared with those obtained with the MP therapy alone. High-dose therapy with transplantation is promising. High-dose therapy combined with autologous bone marrow transplantation improves the response rate, event-free survival (EFS), and overall survival (OS) in patients with myeloma, demonstrated in the prospective, randomized trial by Attal et al. Total therapy by Barlogie et al. consisted of non-cross-resistant induction regimens, followed by a double autotransplantation (AT) procedure. Compared with the outcome of patients receiving standard therapy, dose intensification with double AT produces not only higher CR rates but also significantly extends EFS and OS in previously untreated patients with myeloma. The reduced mortality rate associated with transplantation, and development of new chemotherapeutic agents will lead to future improvements of the therapy for multiple myeloma.
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PMID:[Progress in the treatment of multiple myeloma]. 923 60

The optimal management of hematopoietic malignancies in the elderly requires the development of specific therapeutic strategies based on the peculiar clinico-biologic features of aged patients. Multiple myeloma arising in elderly patients remains at this time an incurable disease, while attention to supportive therapy and palliation can make a great impact on the quality of life. Fortunately advances have been made in last years in this field. Therapy at the time of diagnosis is usually recommended for patients with symptomatic disease, or for those who may be asymptomatic, but have evidence of high tumor burden of a biologically aggressive disease, and may be expected to progress and develop complications over a short period of time. Melphalan combined with prednisone remains the standard therapy choice in elderly patients. Radiotherapy maintains an important place in the palliation of destructive bone disease in poorly controlled myeloma, particularly in elderly patients. In Acute Myelogenous Leukemia, age has been concordantly reported as an adverse prognostic indicator in affecting both remission rates and survival. The overall unsatisfactory therapeutic results appear connected with host-related factors, and intrinsic differences in the biology of leukemia. Patients with standard risk should be included in collaborative trials aimed at improving the long-term results of conventional therapy. Patients with high risk and unfavorable prognostic factors, could be enrolled in controlled studies aimed at better assessing, in the elderly, the long term results of newer drug combinations. A watch and wait strategy, consisting of transfusion support and leukocytosis control, should be limited to patients with extremely poor performance status (PS), very limited life-expectancy and/or severe comorbidity displaying unfavorable biologic factors, including secondary Acute Myelogenous Leukemia.
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PMID:Treatment of multiple myeloma and acute myelogenous leukemia in the elderly: an update. 925 11


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