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

Autologous peripheral blood stem cell transplantation (APBSCT) is used similarly to autologous bone marrow transplantation (ABMT) to reconstitute bone marrow following myeloablative therapy in patients with proliferative diseases of the blood. Eight patients with recurrent and refractory lymphoma (3 HD, 4 NHL) and multiple myeloma aged 17-55 were included into the study. Peripheral blood stem cells following their prior mobilisation with cyclophosphamide 4-7 g/m2 and/or G-CFS or Dexa-BEAM + G-CSF were collected by subsequent leukaphereses on Fenwal CS3000. Nucleated cells were separated by sedimentation, cryopreserved in a programmed freezer and then stored at-196 degrees C. Bone marrow has been additionally collected in one patient. Conditioning treatment prior to transplantation consisted of BCNU, etoposide and cyclophosphamide (CBV) in lymphomas and melphalan in multiple myeloma. Collected material with mean cellularity 5.52 x 10(8)/kg and mean CD34+ contents 6.27 x 10(6)/kg was reinfused by central line. G-CSF was given in 5 patients to hasten the bone marrow recovery. All patients fully recovered and left hospital on average 35.5 days following transplantation. No signs of relapse were seen throughout the observation period (mean 349.5 days). Neutrophils > 0.5 G/1 were obtained on day + 20, > 1.0 G/1 on day 30, platelets > 50 G/1 on day 29, > 100 G/1 on day 53, reticulocytes > 0.015 on day 30, erythrocytes transfusions were needed up to day 39. Presented outcomes together with other reports indicate, that APBSCT is a highly efficient way to rescue repeatedly relapsing patients with proliferative diseases of the lymphatic systems, even those presenting with changes in the bone marrow (neoplasmatic infiltrate, hypoplasia or fibrosis).
 ...
PMID:Autologous peripheral blood stem and progenitor cells transplantation as a valid treatment approach in recurrent, refractory lymphoma. 874 94

To improve the outcome for patients with relapsed or refractory multiple myeloma (MM), we combined idarubicin (Ida), dexamethasone and interferon (IFN) in a new regimen, 'I-Dexa'. Here we report our results of a phase I/II study using the I-Dexa protocol in an outpatient setting. A total of 31 patients were enrolled. Most patients were heavily pretreated with a median of two different chemotherapy regimen (range, 1-4). All but four patients had advanced disease (stage III). The dose of Ida was escalated to define the maximal tolerated dose (MTD) in this regimen. Four patients were treated with 5 mg/m2 and 27 patients with 7.5 mg/m2 Ida (day 1, i.v.). Dexamethasone was given at a fixed dose of 20 mg per os daily on days 2-5 and 11-14. Treatment was repeated at day 21 and consisted of up to six cycles. Patients who achieved a response or stable disease received IFN maintenance. IFN was administered three times weekly at a dose of 3 x 10(6) U/day s.c. until relapse. At the time of evaluation, 125 courses of I-Dexa were analyzed. The MTD of Ida in this regimen was 7.5 mg/m2. Hematological toxicity was mild including 5% leukocytopenia, 3% thrombocytopenia and 1% anemia (WHO grade III) at dose level 2. The MTD was defined by nonhematological toxicities including two WHO grade IV infections and one renal failure. The overall response rate including stable disease was 62.5% (PR: nine patients, 37.5%). So far, nine patients have been treated with IFN maintenance therapy with a median duration of 7 months (range, 1-16). In conclusion, I-Dexa can be given safely in an outpatient setting and is effective for the treatment of relapsed and refractory MM.
 ...
PMID:A phase I/II study of idarubicin, dexamethasone and interferon-alpha (I-Dexa) in patients with relapsed or refractory multiple myeloma. 943 39

In multiple myeloma (MM), allogeneic bone marrow transplantation may produce complete and durable responses, but is accompanied by significant transplant-related mortality (TRM). To assess feasibility and possible advantages offered by the use of allogeneic, growth factor-primed PBSC instead of marrow, we analyzed the data of 10 patients with MM (IgG = 6, IgA = 1, BJ = 2, non-secreting = 1; stage II = 1, stage III = 8, plasma-cell leukemia = 1) who received an allogeneic transplant with PBSC. Their age ranged between 35 and 53 years (median 45). All were HLA-identical to their sibling donors. Prior to allograft, six patients received standard-dose chemotherapy (DAV or CY-Dexa) and four a sequential intensified scheme with autologous PBSC support. At the time of transplantation, three patients were in CR, three in PR, three had refractory disease, one progressive disease. Patients were conditioned with busulfan-melphalan (n = 9) or busulfan-cyclophosphamide (n = 1), and were allografted with unmanipulated PBSC obtained by apheresis after treatment with G-CSF alone (n = 6) or GM-CSF followed by G-CSF (n = 4). All patients engrafted, with 0.5 x 10(9)/l PMN and 50 x 10(9)/l platelets on (median) day 13. Four patients had > or =grade II acute GVHD (grade II in 3, grade III in 1). Following allograft, CR was achieved in 71% patients. Eight are currently alive, with six in CR at a median of 18.5 months (range 7-28) from the transplant. Two patients died, 1 and 4 months from the allograft, respectively, and one is alive with progression. A PCR analysis of IgH rearrangement showed that residual disease was no more molecularly detectable in four out of seven evaluated patients following allograft. The results suggest that PBSC may improve the therapeutic efficacy of allogeneic transplant in MM, not only by a reduction of TRM but also by an improvement of rate and quality of response.
 ...
PMID:Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma. 973 68

To look for new candidates for agents to use in maintenance therapy for myeloma patients, the growth inhibitory effects of a 3-hydroxy-3-mehtylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin), simvastatin, was analyzed using human myeloma cell lines. Several investigations have indicated growth reduction in certain lineages of cancer cells including one report on myeloma, and inhibitory effects of statins on GTPases and involving MAP-kinases. Most (12 out of 13) myeloma lines examined showed growth inhibition when cultured with various concentrations (1-30 microM) of simvastatin in a dose-dependent manner. Simvastatin in combination with other biological response modifiers such as ATRA or DEX had additional effects on growth. In addition, anti-oxides prevented the simvastatin-induced growth inhibition and apoptosis. Furthermore, myeloma cells treated with simvastatin clearly showed inactivation of various MAP-kinase pathways such as ERK1/2, MEK1/2, JNK, and p38. Based on these findings, statins may be suitable for clinical usage in maintenance therapy for myeloma patients.
 ...
PMID:Effects of an HMG-CoA reductase inhibitor, simvastatin, on human myeloma cells. 1506 46

Patients with myeloma, treated on the thalidomide arm of total therapy 2 (TT2), had a higher complete response (CR) rate and improved event-free survival (EFS) but not overall survival (OS). To evaluate the benefit of TT2's posttandem autotransplant consolidation chemotherapy and dexamethasone maintenance, outcomes were compared on TT2 without thalidomide (n = 345; median follow-up, 3.5 years) and on predecessor trial TT1 (n = 231; median follow-up, 11.5 years). CR rates were similar (43% vs 41%); however, 5-year estimates of continuous CR (45% vs 32%, P < .001) and 5-year EFS (43% vs 28%, P < .001) were superior with TT2, with a trend for improved OS (62% vs 57%; P = .11). OS was also superior among patients achieving CR and receiving the second transplantation early after the first transplantation. Superior EFS and OS with TT2 versus TT1 was noted in the two thirds presenting without cytogenetic abnormalities (CAs); 4-year posttandem transplantation OS for patients with CAs was 47% with TT1 and 76% with TT2 when combination chemotherapy rather than DEX was applied for consolidation (P = .040). Thus, TT2 (without thalidomide) improved OS of patients without CAs; those with CAs benefited from posttransplantation consolidation chemotherapy. The favorable effects of CR and rapidly sequenced second transplantation attest to the validity of a melphalan dose-response effect in myeloma.
 ...
PMID:Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies. 1632 68

Hematopoietic stem cells (HSC) transplantations are usually performed 24-48 hours after the end od high-dose chemotherapy (HDC). It is possible, however, that at that time the transplanted HSC can be affected by the administered drugs. We report the results obtained in 30 patients (pts) with hematological malignancies (multiple myeloma - 14, Hodgkin's disease -6, non-Hodgkin's lymphomas -4, chronic myeloid leukemia -6) treated with HDC with peripheral blood stem cell transplantation (PBSCT). The following HDC regimens were applied: melphalan - 14, Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) - 10 and BuCy2 (busulfan, cyclophosphamide) - 6. To evaluate the impact of HDC on the growth ability of less /14/ and more /7/ mature CFU-GM, sera were taken directly before cytoreductive chemotherapy, on the last day of HDC (0 day) and on days 1, 2, 3, 4 and 5 after the end of HDC. After melphalan, for CFU-GM/14/ the following results were received: days 0 - 54 +/- 9, 1 - 55 +/- 9, 2 - 68 +/- 12, 3 - 82 +/- 10, 4 - 95 +/- 8,5 - 100 +/- 8% and for CFU-GM/7/: days 0 - 60 +/- 11, 1 - 59 +/- 8, 2 - 72 +/- 11, 3 - 80 +/- 7, 4 - 90 +/- 9, 5 - 105 +/- 7%, determined as a percentage of those obtained before HDC (100%). After Dexa-BEAM, for CFU-GM/14/: days 0 - 45 +/- 13, 1 - 49 +/- 8, 2 - 59 +/- 12, 3 - 85 +/- 15, 4 - 96 +/- 9, 5 - 106 +/- 11%, and for CFU-GM/7/: 0 - 43 +/- 15, 1 - 50 +/- 9, 2 - 63 +/- 11, 3 - 89 +/- 11, 4 - 98 +/- 11, 5 - 110 +/- 8%. In case of BuCy2, for CFU-GM/14/: days 0 - 55 +/- 13, 1 - 67 +/- 7, 2 - 69 +/- 15, 3 - 85 +/- 10, 4 - 103 +/- 12, 5 - 108 +/- 7% and for CFU-GM/7/: days 0 - 50 +/- 12, 1 - 71 +/- 6, 2 - 76 +/- 16, 3 - 98 +/- 9, 4 - 105 +/- 11, 5 - 101 +/- 8%. In all pts PBSCT were infused 72 hours after HDC. The median time to reach granulocytes > 0.5 G/l and >1.0 G/l was 12 (8-17) and 13 (9-18) days, respectively. The recovery of platelets >20.0 G/l and >50. 0 G/l occured after 17 (9-48) and 25 (11-54) days, respectively. We conclude that the suppressive effect of the sera taken on days 0-2 on the CFU-GM growth depends on the HDC-regimen. We have also shown that third day after completion of HDC is the optimal time for the infusion of HSC. The time of hematological reconstituton is related in all investigated pts and independently on the HDC-program (p>0.05).
 ...
PMID:[Suppressive effect of high-dose chemotherapy (HDC) on the clonal growth of grafted peripheral blood granulocyte progenitors is reduced 72 hours after completion of HDC]. 1647 25

Thalidomide is active both as single agent and in combination-therapy against refractory or relapsing multiple myeloma. Eigth patients previously treated were given Thalidomide 100mg/daily plus Dexametasone 40mg/daily for four days each month (Thali-Dexa) and followed for response, prognostic factors and side effects. Two patients had early death (one from massive cerebral ischemic stroke, the other from dementia and progressive renal failure), one patient progressed during Thali-Dexa (thalidomide 200mg) and was rescued with chemotherapy, two patients required increasing thalidomide dosage (to 200 and 400mg, respectively) because of progressive disease, three patients had stable disease remission lasting from 4m+ to 16m+. Thali-Dexa is a useful agent but age and vascular/metabolic diseases may increase the risk of severe side effects. Early decrease in erythrocyte sedimentation rate seems to correlate with better disease control.
 ...
PMID:Low-dose thalidomide plus monthly high-dose oral dexamethasone (Thali-Dexa): results, prognostic factors and side effects in eight patients previously treated with multiple myeloma. 1676 19

PURPOSE Thalidomide-dexamethasone (THAL-DEX) is standard induction therapy for multiple myeloma (MM). Tandem melphalan-based transplantations have yielded superior results to single transplantations. Phase II trial S0204 was designed to improve survival results reported for the predecessor, phase III trial S9321 by 50%. PATIENTS AND METHODS Newly diagnosed patients with MM were eligible for S0204 with THAL-DEX induction, tandem melphalan-based tandem transplantation, and THAL-prednisone maintenance. Results Of 143 eligible patients, 142 started induction, 73% completed first transplantation, 58% completed second transplantation, and 56% started maintenance. The quantity of stem cells required for two transplantations was reached in 88% of 111 patients undergoing collection, 74% of whom completed both transplantations. Partial response, very good partial remission, and complete response were documented after 12 months of maintenance therapy in 87%, 72%, and 22% of patients, respectively. During a median follow-up time of 37 months, 4-year estimates of event-free and overall survival were 50% and 64%, respectively. Survival outcomes were superior for International Staging System (ISS) stage 1 disease, when lactate dehydrogenase (LDH) levels were normal and a second transplantation was applied in a timely fashion. CONCLUSION Both overall survival (P = .0002) and event-free survival (P < .0001) were significantly improved with S0204 compared with S9321 when 121 and 363 patients, respectively, were matched on ISS stage and LDH.
 ...
PMID:Phase II study of thalidomide plus dexamethasone induction followed by tandem melphalan-based autotransplantation and thalidomide-plus-prednisone maintenance for untreated multiple myeloma: a southwest oncology group trial (S0204). 1954 5

The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P < .001; 63% vs 16%, P < .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LEN-DEX (neutropenia grade 3 or 4: 21% vs 5%, P < .001; thromboembolic events despite aspirin prophylaxis: 23.5% [initial LEN-DEX or crossover] vs 5%; P < .001). This trial was registered at www.clinicaltrials.gov as #NCT00064038.
 ...
PMID:Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). 2087 54

Multidrug resistance represents a major obstacle for the chemotherapy of a wide variety of human tumors. To investigate the underlying mechanisms associated with resistance to anti-cancer drugs, we established anti-cancer drug-resistant multiple myeloma (MM) cell lines RPMI8226/ADM, RPMI8226/VCR, RPMI8226/DEX, and RPMI8226/L-PAM, the 50% inhibitory concentration values of which were 77-, 58-, 79-, and 30-fold higher than their parental cell lines, respectively. The resistant cell lines overexpressed MDR1 and survivin, or showed decreased Bim expression. These results indicated that regulating these factors with inhibitors might be a viable approach to increasing the susceptibility of quiescent MM cells to chemotherapy.
 ...
PMID:Overexpression of MDR1 and survivin, and decreased Bim expression mediate multidrug-resistance in multiple myeloma cells. 2281 74


1 2 3 Next >>