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)

Multiple myeloma (MM) has an incidence of approximately four per 100,000 per year. Ninety-nine percent of patients with MM have a monoclonal (M-) protein in the serum or urine during the course of their disease. MM must be differentiated from smoldering multiple myeloma (SMM), which has an M-protein value of more than 30 g/l and more than 10% plasma cells in the bone marrow, but no other features of MM. The plasma cell labeling index (PCLI) and the presence of circulating plasma cells in the peripheral blood help to differentiate monoclonal gammopathy of undetermined significance and SMM from MM. The current median duration of survival with chemotherapy is about three years. Patients with low PCLI and low &bgr; subset2-microglobulin values have a median duration of survival of approximately six years. Melphalan and prednisone produce an objective response in 50% to 60% of patients. Combinations of chemotherapy produce a higher response rate, but the survival rate is not different. Allogeneic bone marrow transplantation is associated with a mortality rate of 25% within six months and an actuarial survival rate of 28% at seven years. Autologous peripheral stem cell transplantation is applicable to more patients and is reported to produce a higher response rate and longer survival than chemotherapy, but most patients will eventually have relapse.
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PMID:Multiple Myeloma: An Overview in 1996. 1038 9

Melphalan was investigated for antitumoral activity using two schedules of exposure (solid versus sequential exposure) in two human cancer cell lines (8226 and A2780). Sequential exposure of melphalan was more effective than solid exposure at the same total dose. The IC50 values averaged 8.2 (solid exposure) and 0.16 microgram/ml (sequential exposure) for 8226 cells (myeloma), and 7.5 (solid) and 0.53 microgram/ml (sequential) for A2780 cells (ovarian carcinoma). Intracellular melphalan accumulation, determined by high-performance liquid chromatography, showed that the area under the intracellular concentration of melphalan versus time curve (between 0 and 30 h) was significantly higher after sequential doses (9.4 micrograms/ml x h) than after solid dose (6.6 micrograms/ml x h). Moreover, intracellular/extracellular concentration ratios indicated that melphalan uptake followed a passive transport system. The increase of both duration of exposure (11 h after solid exposure versus 20 h after sequential doses) and intracellular concentrations 5-6 h after the beginning of the experiment (approximately 3 times higher after sequential doses) indicate sequential administration of melphalan could be more effective than solid exposure.
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PMID:Influence of the schedule of exposure on the cytotoxic effect of melphalan on human 8226 and A2780 cells. 1065 34

A 48-year-old patient with IgA k multiple myeloma received a BMT from his HLA-matched sibling. After transplantation, the disease relapsed. Melphalan therapy followed by reinfusion of haemopoietic blood stem cells collected from the patient led to the improvement of the clinical status, although mixed chimerism and an elevated serum IgA persisted. Successful donor immunisation against an immunogenic preparation of the recipient monoclonal protein was performed before the infusion of donor T lymphocytes (DLI) into the patient. Ten weeks after the lymphocyte infusions, no monoclonal band was evidenced and donor complete chimerism was detected. The patient did not develop GVHD. Once complete remission was achieved, the idiotype vaccine was administered to the patient. Nineteen months after DLI, the patient remains in remission. Bone Marrow Transplantation (2000).
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PMID:Infusion of lymphocytes obtained from a donor immunised with the paraprotein idiotype as a treatment in a relapsed myeloma. 1082 74

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.
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PMID:Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan. 1092 34

To evaluate factors affecting mobilisation and harvest and to calculate the economic costs of autologous stem cell transplantation in multiple myeloma (MM) we analysed 29 consecutive patients who had been transplanted at the Nijmegen University Hospital between January 1992 and February 1999. Thirteen patients had been treated with three or more melphalan cycles before transplantation (melphalan group), while four of the remaining 16 patients (no-melphalan group) had only received one melphalan cycle with an interval of one year or longer before harvest. The two groups were analysed for differences in mobilisation, harvest and the costs. Collection of a sufficient number of peripheral stem cells failed in 4 patients in the melphalan group, and these patients were transplanted with both bone marrow and peripheral stem cells. The greater need for growth factors (median 6,400 microg vs 4,500 microg) and the longer duration of admission (median 8 days vs 3 days) for mobilisation in the melphalan group increased significantly (p=0.01) the total mobilisation costs (median fl 13,876 vs fl 6,101). The greater number of apheresis sessions (median three) and the additional bone marrow harvests for patients who could not achieve a sufficient number of stem cells, increased significantly (p<0.001) the total harvest costs (median fl 9,690 vs fl 1,615) in the melphalan group. This resulted in significantly (p=0.008) higher overall costs of the procedure (median: fl 49,576 vs fl 35,889). The haematopoietic recovery of all groups was similar. The no-melphalan group was subdivided in two groups based on the median number of chemotherapy cycles before harvest. The heavily treated group had received more than 5 chemotherapy cycles and the moderately treated group four cycles or less. The median overall costs of these two groups were comparable (median fl 36,837 vs fl 34,351). This study suggests that the administration of stem cell toxic melphalan before harvest contributes to administration of more dosages of growth factor, longer admission duration for mobilisation and higher number of leukaphereses in order to collect sufficient number of stem cells. This resulted in significantly higher overall costs. More cycles of chemotherapy without melphalan did not increase significantly any studied parameter nor the total costs of procedure. Melphalan therapy or heavy pre-treatment did not prolong the repopulation interval, probably due to the infusion of similar number of progenitor cells.
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PMID:Impact of chemotherapy on the mobilisation, harvest and economic costs of autologous peripheral stem cell transplantation in patients with multiple myeloma. 1104 15

Melphalan and prednisone have been the backbone in myeloma therapy for more than 40 years. New developments in chemotherapy and supportive therapy, achieved during the two decades which preceded the use of high-dose chemotherapy with stem cell rescue, have not changed the overall prognosis. A study of high-dose melphalan with autologous stem cell support on 274 patients < 60 years, performed by the Nordic Myeloma Study Group, has shown a prolongation of the median survival by 1.5 years. The results confirm that this therapy is a major step forward in myeloma therapy. Cost-utility and quality-of-life studies show that high-dose therapy has acceptable costs and leads to a favorable long-term quality-of-life.
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PMID:[High-dose melphalan with stem cell support is now an established myeloma therapy. Treatment of myeloma from a 30-year perspective]. 1110 44

High-dose therapy in multiple myeloma (MM) appears to be superior in terms of event-free survival and overall survival compared with conventional therapy. Melphalan-based high-dose therapy increases complete remission rates from 5% to 50% and extends event-free survival beyond 3 years and overall survival beyond 6 years. Critical disease features associated with durable complete remission, event-free survival, and overall survival include the absence of chromosome 13 deletion, low beta(2)-microglobulin, and low C-reactive protein levels. Data on 1,000 patients enrolled in tandem high-dose trials show that chromosome 13 deletion is an important prognostic feature. The timely application of a second cycle of high-dose therapy extends event-free survival and overall survival markedly in MM patients with low beta(2)-microglobulin levels. Long-term results of the total therapy trial indicate that patients who do not have chromosome 13 deletions and present with low C-reactive protein and beta(2)-microglobulin levels have longer complete remissions than patients lacking these prognostic factors. Thalidomide shows clear evidence of antitumor activity possibly because of its antiangiogenic activity. Magnetic resonance imaging (MRI) indicates that bone marrow lesions become smaller or disappear while patients receive dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation chemotherapy and that patients who have a compete remission after diagnostic MRI have a superior event-free and overall survival than those who still have persistent MRI lesions. Prospective trials are underway to evaluate the effectiveness of consolidation therapy (total therapy II).
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PMID:High-dose therapy and innovative approaches to treatment of multiple myeloma. 1130 5

High dose chemoradiotherapy with autologous peripheral blood progenitor cell transplantation (PBPCT) may improve outcome in myeloma. Melphalan is an effective drug in the treatment of myeloma, but is potentially toxic to progenitor cells. We studied 8 patients receiving intermittent intravenous melphalan (25 mg/m2) as induction therapy before PBPCT to assess engraftment characteristics post-transplantation. Comparison was made with an age-matched control group of patients with non-Hodgkins lymphoma who had not received melphalan during induction therapy. There was correlation (P=0.037) between the dose of melphalan per kg body weight given, premobilization, and days to neutrophil engraftment, but no significant difference between the two groups in neutrophil recovery. The study group had delayed platelet recovery (P=0.01) and required more platelet support post-transplantation (P=0.05). 3-4 weekly melphalan (25 mg/m2) up to 6 courses was delivered to patients who went on to PBPCT without significantly influencing neutrophil recovery but with a negative impact on platelet recovery.
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PMID:The effects of prior induction therapy with melphalan on subsequent peripheral blood progenitor cell transplantation for myeloma. 1148 52

A 75-year-old woman was referred to us because of cough, high fever and skin erythema in April 1999. Malignant lymphoma (diffuse mixed cell type) was previously diagnosed in 1990 and she achieved complete remission after treatment with a series of CHOP regimen treatments. In 1998, multiple myeloma (IgG lambda type) was diagnosed and she was treated with a combination of melphalan and prednisolone. On physical examination, superficial lymphadenopathy and skin erythema were noted. Biclonal gammopathy (IgG kappa/lambda) was shown in serum, and Bence Jones protein in urine. Computed tomography showed pleural effusion and swelling of paraaortic lymph nodes. The bone marrow examination showed an increased number of abnormal plasma cells (19.2%) and no evidence of lymphoma. Left axillary lymph node biopsy revealed that she had non-Hodgkin's lymphoma (immunoblastic lymphadenopathy-like T cell lymphoma). She was treated with the CHOP regimen at reduced doses for both diseases. The lymphoadenopathy reduced after 6 courses of CHOP and 4 courses of CHOPE (CHOP + VP16), however, she had bone pain on November 1999 and received treatment with MCNU-VMP (MCNU + VDS + L-PAM + PSL). Her rib pain improved, but she died of systemic infection of herpes zoster virus. We report here a rare case of malignant lymphoma concomitant with multiple myeloma.
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PMID:[A case of malignant lymphoma concomitant with multiple myeloma]. 1160 18

Several trials have shown the activity of thalidomide (THAL) in relapsed multiple myeloma (MM) patients failing PBSCT or conventional chemotherapy. PBSCT is considered standard treatment for most patients requiring therapy for MM; however, patients with VAD-resistant disease may not be able to receive PBSCT due to rapidly advancing disease. We report four cases of VAD-refractory MM salvaged with THAL + VAD followed by PBSCT. All patients underwent stem cell mobilization with cyclophosphamide (Cy) (4.5 g/m(2)) and GMCSF. Melphalan (140-200 mg/m(2)) was given as conditioning. All patients engrafted within 12-16 days after PBSCT. Day +100 evaluation showed the following: very good partial response (n = 1) and complete response (n = 3). After a median follow-up to 153 days, two patients continue to take THAL with no signs of disease progression. One patient developed CHF and was taken off THAL while another patient has died of progressive disease while on THAL (MTD 50 mg). In conclusion, VAD-refractory patients were salvaged with the addition of THAL to VAD. They were subsequently able to undergo autologous PBSCT for MM, which will likely improve their overall survival. This suggests that THAL and other related immunomodulatory drugs may prove useful for initial MM therapy in combination with standard chemotherapy followed by PBSCT.
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PMID:Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT. 1285 10


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