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)

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272-4760), 306 (range, 111-408) and 143 (range, 91-282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10(6) platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2-14.3) raised in secondary polycythemia (range, 26-104) compared with normal controls (range, 9.7-31.1), P<0.01. In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.
 ...
PMID:Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera. 1236 69

Renal failure frequently complicates the course of multiple myeloma. Factors that determine the development of myeloma kidney include a high rate of light chain excretion, biochemical characteristics of light chain, and concurrent volume depletion. There are two main pathogenetic mechanisms; i.e. direct tubular toxicity and intratubular cast formation. Therapeutic measures include chemotherapy, bone marrow or peripheral blood stem cell transplantation, hyperhydration, plasmapheresis, dialysis, solving of hypercalcemia, treatment of anemia with erythropoietin, and avoidance of nephrotoxic drugs and radiocontrast agents. Experimental approach includes administration of colchicines and alkalinization of the urine.
 ...
PMID:Myeloma kidney: pathogenesis and treatment. 1239 20

Anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM). Besides the altered cytokine network, chronic erythropoietin deficiency, blood loss and hemolysis, we have shown that deregulated myeloma cell apoptosis may contribute to progressive destruction of the erythroid matrix by inducing erythroblast cytotoxicity. To exert this effect, highly malignant plasma cells overexpress both Fas-ligand (Fas-L) and TRAIL, which efficiently trigger the death of immature erythroblasts. In view of severe progression of MM in patients with Fas-L/TRAIL-based anemia, overexpression of these apoptogen receptors may characterize a peculiar cytotoxic-apoptogenic phenotype in malignant plasma cells. Early immunophenotyping of myeloma cells could thus help to identify patients with a higher risk of erythropoiesis exhaustion.
 ...
PMID:Anemia in multiple myeloma: role of deregulated plasma cell apoptosis. 1240 May 94

Significant advances have been made in the development of targeted interventions for hematologic malignancies. Progress has been made in defining the molecular pathogenesis of human leukemias. Data indicate that nonrandom, somatically acquired translocations, inversions, and other abnormalities occur in many acute leukemias. In the treatment of acute promyelocytic leukemia (APL), targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy leads to dramatic improvements in disease-free survival. Imatinib mesylate, a signal transduction inhibitor that inhibits tyrosine kinase activity, the protein product of the ABL proto-oncogene, has remarkable activity in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL). Farnesyltransferase inhibitors (FTIs), a promising class of agents that target multiple pathways including Ras proteins, are potential anticancer therapy for a wide range of malignancies, including leukemias and myelodysplastic syndromes (MDS). There also is evidence that recombinant human erythropoietin therapy (r-HuEPO) can benefit patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. This supplement will discuss advances in our understanding of human leukemias, including the use of unconjugated monoclonal antibodies such as Campath-1H (Wellcome, Beckenham, UK, and Ilex Oncology, San Antonio, TX) and rituximab and immunoconjugates such as gemtuzumab ozogamicin and BL-22. Although these novel therapies are beginning to fulfill their promise, continued research efforts are needed to determine the optimal role of targeted therapy in acute and chronic leukemias.
 ...
PMID:Advancing the treatment of hematologic malignancies through the development of targeted interventions. 1244 45

Anemia is prevalent among cancer patients with hematologic malignancies, with fatigue and weakness, major symptoms of anemia, contributing to diminished quality of life (QOL). Data from several randomized, placebo-controlled clinical trials and three large community-based studies in patients with hematologic malignancies indicate that recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct anemia, reduce transfusion requirements, and improve QOL. Moreover, a positive relationship has been found between increased hemoglobin (Hb) levels and improvements in QOL assessments, regardless of disease state, with the greatest incremental improvement occurring when Hb increases from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). This suggests that patients with mild-to-moderate anemia may achieve the greatest QOL benefit from epoetin alfa therapy. Evidence from community-based studies suggests that epoetin alfa administered once weekly has a similar safety and efficacy profile as three-times-weekly administration. Further research is ongoing with less frequent dosing regimens. The beneficial effects of epoetin alfa therapy have been reported in studies involving patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. Evidence also exists that epoetin alfa can benefit patients with myelodysplastic syndromes (MDS), although these results have not been as impressive. Combining epoetin alfa with other cytokine growth factors may confer some additional benefit in these patients, but more rigorous investigation is required.
 ...
PMID:Epoetin alfa as a supportive measure in hematologic malignancies. 1244 49

There has been no improvement in the treatment of multiple myeloma (MM) during the last decades and two meta-analyses of randomized trials recorded no significant survival benefit for combination chemotherapy compared to the classic melphalan-prednisone combination. However the past 15 years has seen several innovative strategies which have dramatically modified the management of MM. In younger patients, high-dose therapy with autologous stem cell transplantation is considered to be superior to conventional chemotherapy and is used as part of front-line therapy. A number of issues have been addressed in recent trials in order to improve the results of autologous transplantation (source of stem cells, conditioning regimen, impact of double transplants, maintenance therapy). Bisphosphonates reduce the incidence of skeletal-related events and improve the quality of life. Recombinant erythropoietin reduces red blood cell transfusion need and improves the quality of life. Thalidomide has been introduced more recently. Phase II studies with thalidomide alone or combined with dexamethasone have shown impressive response rates and this drug is currently being evaluated as part of front-line therapy. Finally, analysis of prognostic factors such as beta 2 microglobulin and cytogenetics define subgroups of patients with a completely different outcome and help the process of selecting therapeutics strategies.
 ...
PMID:Management of multiple myeloma. 1261 98

The prevalence of tumour anaemia in patients with multiple myeloma is greater than 80%. At the time of diagnosis 20% of these patients are already anaemic. In about 70% of patients with multiple myeloma, recombinant human erythropoietin (r-HuEPO) leads to a reduction in transfusion frequency, resulting in a drop in transfusion- related side-effects like infections and immune reactions, iron overload and hyperviscosity which often negatively influence the course of disease. A further reason for the use of erythropoietin is to achieve and maintain high haemoglobin levels (11-12 g/dl), which are of considerable prognostic significance in patients with multiple myeloma. Increasing Hb levels with r-HuEPO also improve the quality of life of patients, thus leading to better therapy compliance. The trade-off between high costs of an erythropoietin treatment and lower indirect costs (infusion material, personal equipment, patient transport costs, etc.) should be evaluated. Nevertheless, an exact definition of patients for whom the use of erythropoietin is beneficial is warranted. The pathogenesis of anaemia and the clinical experiences of erythropoietin in patients with multiple myeloma are discussed.
 ...
PMID:Use of erythropoietin in patients with multiple myeloma. 1262 23

Chronic anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM) as a consequence of the B cell malignancy. Its pathogenesis is multifactorial. Besides the altered inflammatory cytokine network, other events are held responsible, namely persistent defect of erythropoietin due to the kidney failure, shortening of red cell survival, accumulation of the serum monoclonal component and platelet dysfunction. Our recent studies have demonstrated that excessive erythroblast apoptosis promoted by myeloma cells drives the appearance of anemia, in particular in patients with severely progressive disease. A number of clinical trials have provided evidence for the effectiveness of recombinant human erythropoietin (rHuEPO-alpha: epoetin alpha) in improving the deregulated erythropoiesis in MM, since it acts as a major erythroid growth factor by exerting a specific anti-apoptotic effect. In the majority of these studies, the long-term treatment of MM-associated anemia with rHuEPO-alpha induced a significant improvement of erythropoiesis, as shown by a stable increase of hemoglobin values (> or = 2g/dL) and reduction of transfusion requirements. In a recent trial which included both a double-blind and an open-label phase, we have documented that rHuEPO-alpha induces a stable improvement of anemia in more than 75% of patients and a significant decrease of fatigue, with an overall recovery of the quality of life. Patients receiving a placebo also achieved similar results in the open-label phase, when they were switched to rHuEPO-alpha.
 ...
PMID:The role of recombinant human erythropoietin alpha in the treatment of chronic anemia in multiple myeloma. 1273 13

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously once weekly (q.w.) was at least as effective as 10,000 t.i.w. administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin (Epo) production. Overall, 241 anaemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, all with serum Epo values </= 100 mU/ml, were randomized to receive the q.w. (n = 119) or t.i.w. (n = 122) regimen for 16 weeks. The primary efficacy criterion, i.e. the time-adjusted area under the haemoglobin-time curve from weeks 5-16, was comparable between the q.w. and t.i.w. groups [difference = - 0.20 g/dl (90% confidence interval - 0.52-0.11)]. Moreover, response rates were high and similar in both arms (72%vs 75%, q.w. and t.i.w. groups respectively). Baseline serum Epo was predictive of response: the lower serum Epo, the higher the likelihood of response (P = 0.002). Thus, epoetin beta administered q.w. is an effective and convenient treatment for anaemia in patients with lymphoproliferative disorders. Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective.
 ...
PMID:Once-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production. 1501 84

This phase 3, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2.25 microg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0.001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1.80 g/dl vs 0.19 g/dl) and after 12 weeks of treatment (2.66 g/dl vs 0.69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0.001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.
 ...
PMID:Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. 1287 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>