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)

Patients with IgG multiple myeloma underwent serial studies of tumor cell kinetics including (1) estimation of the total body myeloma cell number (TBMC), (2) measurement of the myeloma cell tritiated thymidine labeling index (LI), and (3) calculation of the total number of myeloma cells undergoing DNA synthesis. Intermittent courses of chemotherapy with cycle-non-specific agents such as melphalan resulted in a marked increase in the LI of myeloma cells in patients who had a 75% reduction in TBMC. The long "plateau" phase of partial remission of myeloma in these patients was associated with a continued high LI: this suggests that the plateau resulted from a balance between the cytoreductive effects of chemotherapy and expansion of the growth fraction (GF) of the tumor. Preliminary attempts to capitalize therapeutically on this expansion of the GF in several patients included administration of the cycle-active agents vincristine and cytosine arabinoside. Vincristine appeared to induce a further reduction in tumor in several patients, although cytosine arabinoside appeared to be ineffective despite clear evidence of its inhibition of DNA synthesis in myeloma cells in vivo. Further clinical studies of the effects of cycle-active drugs on myeloma appear to be warranted; however, successful exploitation of the dynamic change in myeloma cell kinetics with chemotherapy will require the use of cycle-active agents with marked selective toxicity for myeloma cells.
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PMID:Expansion of the growth fraction in multiple myeloma with alkylating agents. 80 4

Five patients with high risk multiple myeloma not responsive to standard chemotherapy were treated by high-dose chemotherapy (Melphalan, Cyclophosphamide) (HDC) and total body irradiation (TBI) followed by autografting with blood stem cells. These cells were previously collected by leukaphereses from eight to twelve occasions during hematopoietic recovery following profound aplasia induced by each course of intensive chemotherapy (Vincristine, Adriamycin, Cyclosphosphamide, Prednisone) when the patient reached a neutrophil count of 1,000/microliters and a platelet count of 100,000/microliters. No patients had evidence of tumor plasmacells in leukaphereses products using cytology, immunocytochemistry and immunofluorescence. At this time the patient 5 is not evaluable because of the short follow-up. One died at day 30 from heart failure. All living patients achieved a complete remission which persisted at a follow-up of 300, 261 and 136 days. Autologous blood derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. Our results indicate the feasibility of this therapeutic approach over allogenic or autologous bone marrow transplantation in selected patients with high tumour mass multiple myeloma.
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PMID:Blood stem cells autografts in patients with high risk multiple myeloma. 197 31

A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
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PMID:Single agent vincristine by infusion in refractory multiple myeloma. 299 7

AL amyloidosis is a serious complication of monoclonal gammopathy. The therapeutic strategy in amyloidosis associated with myeloma is to decrease the amyloidogenic precursor synthetised by the monoclonal plasmocytic proliferation. However, when systemic amyloidosis complicates a so called "benign" monoclonal gammopathy, this therapeutic approach is debatable. We report 10 cases of AL amyloidosis without myeloma treated by chemotherapy. Eight patients were initially given alkylating agents (cyclophosphamide or melphalan) which had no effect on the clinical progression of their systemic amyloidosis or on the plasma concentrations of the precursor. A limited open clinical trial including 4 patients was then undertaken based on the Vincristine, Adriamycine, Dexamethasone combination recently proposed for cases of resistant myeloma. A 50% reduction in the serum monoclonal protein was observed in 2 patients with this treatment. However, the mean survival of the 10 patients (25 months) was not longer than that previously reported for patients receiving more conventional treatment. The results of this limited trial indicate the need for further controlled therapeutic trials with larger numbers of patients in order to assess the effect of polychemotherapy in patients with AL amyloidosis.
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PMID:[Treatment of AL amyloidosis without myeloma]. 320 24

Seventy-five patients with previously untreated multiple myeloma were randomly treated with the association of Peptichemio, Vincristine and prednisone (PTC-VCR-P) or of melphalan and P (MPH-P) for first induction therapy. After induction, all responsive patients received MPH and P until relapse, while unresponsive patients received it until unequivocal evidence of disease progression was observed. A second induction therapy with PTC-VCR-P was then administered, except to patients resistant to this association at first induction (who received combination chemotherapy which included cyclophosphamide and adriamycin). The response rate was 58% in the PTC-VCR-P and 41% in the MPH-P group (P greater than 0.05). The PTC-VCR-P responsive patients experienced a median duration of response shorter than MPH-P responsive patients (20.3 vs 39.7, P = 0.041). Median survival from the start of treatment was 26.2 months in the PTC-VCR-P and 54.1 months in the MPH-P group of patients (P = 0.039). Stage I and II myelomas had the same response rate to PTC-VCR-P and to MPH-P, but their survival was shorter on PTC-VCR-P than on MPH-P (P = 0.014). Stage III myelomas responded more frequently to PTC-VCR-P than to MPH-P (P less than 0.02) and there was a trend to survive longer on PTC-VCR-P than on MPH-P (22.0 vs 12.5 months, P greater than 0.05).
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PMID:Peptichemio, vincristine and prednisone versus melphalan and prednisone as induction therapy in multiple myeloma. 377 37

Impressive results have recently been reported in 29 cases of advanced refractory myeloma treated with 4-d infusions of Vincristine and Adriamycin (VAD). We report our own experience with this protocol in 13 cases of myeloma and related lymphoproliferative disorders. In 2 of these cases, VAD was used as first line treatment. Objective responses were seen in two-thirds of cases and the major complication of therapy was infection, predominantly bacterial in nature.
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PMID:The efficacy and toxicity of VAD in the treatment of myeloma and related disorders. 381 40

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.
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PMID:Treatment of multiple myeloma: a randomized study of three different regimens. 390 May 91

Vincristine 0.25 mg/m2 by IV push and bleomycin 5 units daily by continuous infusion were given on days 1, 2, 3 and 4, together with prednisone 1,000 mg/m2 po in 4 divided doses either on days 1, 3, 5, and 7 (6 patients) or on days 1 and 3 (11 patients) to 17 patients with various lymphoproliferative diseases who had failed their previous treatment program. Fourteen were leukopenic and/or thrombocytopenic. Of 10 patients with non-Hodgkin's lymphoma 2 achieved complete remission and 5 a partial response. Both patients with Hodgkin's disease achieved partial response. A decrease in plasma M protein (median decrease 51%) was observed in 3/3 patients with multiple myeloma and 2/2 with Waldenstrom's macroglobulinemia. Decrease in tumor cell infiltration by 48%, 58% and 100% was observed in 3 patients (2 with macroglobulinemia and 1 with myeloma) in the bone marrow. Leukopenia of less than 3,600/mm3 and thrombocytopenia of less than 70,000/mm3 reverted to normal in 5/7 and 7/10 patients, respectively. Remission duration ranged from 4 to 35+ weeks (median 17 weeks). Three patients had severe GI bleeding. Psychosis controlled by phenothiazines was observed in one, and bleomycin toxicity (anaphylaxis, skin rash, and lung toxicity, one each) was observed in 3 patients. No severe neurotoxicity was observed.
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PMID:Treatment of refractory lymphoproliferative diseases with daily, low-dose vincristine, continuous infusion of bleomycin, and high-dose prednisone. 620 45

In order to study the response of patients with multiple myeloma of the bones (MM) to various anti-cancer drugs (Melphalan M, Cyclophosphamide Cy, Nitrosourea NU, Vincristine V, Adriamycine A and Prednisone P), 70 MM received the following treatment : 1) Induction therapy : a) M and P or b) M and Cy and P ; 2) Levelling with partial or complete response : V Cy P (in case a) or V M Cy P (in case b) ; 3) Relapse : A and NU. The following results were obtained : 1) Only 42.6% of patients respond to induction therapy ; 2) Fewer than 10% of patients showing a response reach a second levelling with Vincristine ; 3) 50% of those not showing a response reach a levelling between --20 and --50 and have prolonged survival ; 4) Only 20% of non responders are improved by Cy P or A and NU. The median actuarial survival is 42 months. Among the responders two poor prognosis factors must be underlined : hypercalcemia and the speed of response.
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PMID:[Value of successive chemotherapy in multiple myeloma of bone. Prospective study over 4 years]. 736 Oct 63

To better detail the status of functional T cell subsets and natural killer cells in multiple myeloma, we undertook a detailed immunophenotypic study of circulating mononuclear cells in myeloma. We studied myeloma patients entered on a large prospective, randomized ECOG chemotherapy trial EST 9486 for patients with newly diagnosed multiple myeloma. All patients were studied prior to entry and then two months after initiation of therapy (e.g. post two cycles of Vincristine, BCNU, melphalan, cyclophosphamide and prednisone (VBMCP)). The chemotherapy protocol was a three-arm protocol utilizing either VBMCP, VBMCP alternating with interferon, or VBMCP with intermittent high dose cyclophosphamide. The major findings in this analysis include significant reductions in the white blood cell count, total lymphocytes, T cell (CD3+), T helper (CD4+), and T suppressor (CD8+) cells, after 2 cycles of VBMCP. However, there was a relative sparing of Natural killer (CD16+) and activated T cell (CD2+, HLADR+) reduction in these same patients. In summary, only two cycles of combination chemotherapy resulted in significant reductions in white blood cell and lymphocyte counts in multiple myeloma patients. All cell types appear to have been reduced by chemotherapy except for activated T cells and natural killer cells. The impact of selective modulation of functional T cells subsets during therapy for patients with multiple myeloma is an important parameter which needs to be addressed in the overall approach to these patients.
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PMID:Sequential phenotyping of myeloma patients on chemotherapy: persistence of activated T-cells and natural killer cells. 771 42


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