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)

Pegylated liposomal doxorubicin has reduced toxicity compared with conventional doxorubicin. In a noninferiority trial randomizing patients to receive pegylated liposomal doxorubicin 40 mg/m(2) and vincristine 1.4 mg/m(2) (maximum, 2 mg) intravenously on day 1 plus reduced-dose dexamethasone 40 mg orally on days 1-4 (DVd; n = 97) or conventional doxorubicin 9 mg/m(2) per day and vincristine 0.4 mg per day continuous intravenous infusion on days 1-4 plus reduced-dose dexamethasone (VAd; n = 95) for >/= 4 cycles. Treatment was repeated every 4 weeks until maximal response, disease progression, unacceptable toxicity, or until patients underwent transplantation. Treatment cost was estimated by applying standard US costs in 2004 to recorded health-care resource utilization units. Outcome measures included response, toxicity, and treatment cost. Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between treatment groups. DVd was associated with significantly less grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), less sepsis, antibiotic use, growth factor support, and alopecia, but more hand-foot syndrome. Study drug costs were significantly higher for DVd versus VAd; however, lower costs for drug administration and supportive care more than offset this difference, resulting in nominally lower overall study drug treatment costs for DVd (DVd, $34,442; VAd, $35,846; P = 0.76). The DVd regimen demonstrated similar efficacy and cost with less toxicity and supportive care compared with VAd. This should improve clinical utility and optimize the opportunity for transplantation.
Clin Lymphoma Myeloma 2007 Apr
PMID:Clinical benefits and economic analysis of pegylated liposomal doxorubicin/vincristine/dexamethasone versus doxorubicin/vincristine/dexamethasone in patients with newly diagnosed multiple myeloma. 1756 53

A 80-year-old man was admitted because of acute-onset thrombocytopenia and renal failure. He was diagnosed with Bence Jones (lambda) -type multiple myeloma associated with sepsis with methicillin-resistant Staphylococcus aureus. On admission, serum amylase activity was elevated to 1,814 IU/l (98% salivary type; S-amylase). Several days after admission, he developed bilateral myelomatous pleuritis. The activity of S-amylase in the effusion was 5,495 IU/l. Myeloma cells in the pleural effusion were positive for cytoplasmic amylase with an antibody against human amylase. High S-amylase activity was detected in the supernatant of cultured myeloma cells in the effusion. Furthermore, S-amylase gene expression was detected by RT-PCR. A diagnosis of amylase-producing multiple myeloma was made. The patient died of renal insufficiency complicated by severe DIC. We report a rare case of amylase-producing myeloma confirmed by immunocytochemistry, culture method, and gene expression.
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PMID:[Amylase-producing multiple myeloma: a case report]. 1808 May 6

We report a fatal case of disseminated strongyloidiasis in a patient with multiple myeloma receiving chemrotherapy. A fifty-seven years old man presented with severe diarrhoea and vomiting, fever, weight loss and dysphagia,due to mouth ulcers. Despite broad-spectrum intravenous antibiotics, albendazole (anti protozoal) and supportive treatment, the patient died of Gram-negative sepsis.
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PMID:A fatal case of gram negative bacterial sepsis associated with disseminated strongyloidiasis in an immunocompromised patient. 1833 31

Multiple myeloma is associated with a high risk of infections. We hypothesized that Fc gamma receptor (FCGR) and myeloperoxidase (MPO) promoter gene polymorphisms influence the risk of infections after induction chemotherapy (IC) and autologous stem cell transplantation (ASCT). Retrospectively, we analysed 136 patient courses of IC and 113 procedures of ASCT. Genetic analyses were made with PCR techniques on genomic DNA. The incidence rate ratio of sepsis during ASCT in patients homozygous for the G-129MPO promoter type was 0.30 (95% CI: 0.09-0.96). The G-463AMPO promoter polymorphism was not associated with the risk of infections. The polymorphisms of FCGR2A, FCGR3A and FCGR3B were not convincingly associated with infections. The NA1 variant of FCGR3B was strongly skewed with other risk factors, and the results in IC and ASCT were conflicting. Further studies of the G-129AMPO promoter as a potential risk modifier for infections are relevant.
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PMID:Infectious complications after chemotherapy and stem cell transplantation in multiple myeloma: implications of Fc gamma receptor and myeloperoxidase promoter polymorphisms. 1845 2

The ubiquitin-proteasome system is the major pathway for intracellular protein degradation and is also deeply involved in the regulation of most basic cellular processes. Its proteolytic core, the 20S proteasome, has found to be attached also to the cell plasma membrane and certain observations are interpreted as to suggest that they may be released into the extracellular medium, e.g. in the alveolar lining fluid, epididymal fluid and possibly during the acrosome reaction. Proteasomes have also been detected in normal human blood plasma and designated circulating proteasomes; these have a comparatively low specific activity, a distinct pattern of subtypes and their exact origin is still enigmatic. In patients suffering from autoimmune diseases, malignant myeloproliferative syndromes, multiple myeloma, acute and chronic lymphatic leukaemia, solid tumour, sepsis or trauma, respectively, the concentration of circulating proteasomes has been found to be elevated, to correlate with the disease state and has even prognostic significance. Similarly, ubiquitin has been discovered as a normal component of human blood and seminal plasma and in ovarian follicular fluid. Increased concentrations were measured in diverse pathological situations, not only in blood plasma but also in cerebrospinal fluid, where it may have neuroprotective effects. As defective spermatozoa are covered with ubiquitin in the epididymal fluid, extracellular ubiquitination is proposed to be a mechanism for quality control in spermatogenesis. Growing evidence exists also for a participation of extracellular proteasomes and ubiquitin in the fertilization process.
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PMID:Extracellular, circulating proteasomes and ubiquitin - incidence and relevance. 1860 90

The aim of the present study was to evaluate the effectiveness of bortezomib combined with epirubicin, dexamethasone, and thalidomide (BADT) for the treatment of multiple myeloma (MM). The BADT regimen consisted of a maximum of eight 4-week cycles of: intravenous bortezomib (1.0 mg/m(2)) and intravenous epirubicin (12 mg/m(2)) on days 1, 4, 8, and 11; dexamethasone (20 mg) on days 1, 2, 4, 5, 8, 9, 11, and 12; and oral thalidomide (100 mg/m(2)) on days 1-28. Twelve patients with MM were included in the study, of whom four had not been previously treated and eight had been previously treated with at least one cycle of a systemic combined regimen. All the patients completed at least two cycles of treatment, with an average of five cycles; the complete response (CR) rate was 83.3% (10/12) and stabilization of disease was 16.7% (2/12). The average number of cycles required to achieve CR was 1.9 (range 1-6). In three patients, mobilization of peripheral blood stem cells allowed a sufficient quantity of CD34+ cells to be harvested for future autotransplantation. The main adverse reactions included peripheral neuropathy (4/12), thrombocytopenia (3/12), electrocardiographic abnormalities (4/12), neutropenia (5/12), and liver function impairment (4/12), primarily grade I-II. Infection occurred in four patients with neutropenia, including one patient who developed sepsis. The estimated 1-year overall survival rate was 91.7 +/- 8.0%, and the estimated 1-year disease-free survival was 75.0 +/- 12.5%. BADT is a highly effective combined regimen, with acceptable toxicity, for the treatment of multiple myeloma.
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PMID:Bortezomib in combination with epirubicin, dexamethasone and thalidomide is a highly effective regimen in the treatment of multiple myeloma: a single-center experience. 1908 17

This study describes a spectrum of renal diseases that can precede the diagnosis of multiple myeloma (MM). Patients presenting manifestations of renal disease were recorded as individual patients of MM. Fifty patients (male 41; female 9) were included in this study. Diagnosis of MM was confirmed by two or more of the following four features: lytic bone lesions, serum or urine monoclonal peak, Bence Jones proteinuria, and greater than 20% plasma cells in bone marrow. Renal disease was present in 42 of 50 (84%) patients before MM was diagnosed. In only eight of 50 (16%) patients, diagnosis of MM preceded the detection of renal disease. Renal diseases consisted of acute renal failure in 26 patients (52%), chronic renal failure in 15 patients (30%) and nephrotic syndrome in 9 patients (18%). Some of the patients with acute or chronic renal failure also had heavy proteinuria. Percutaneous renal biopsy was done in 17 patients. Renal histopathology showed amyloidosis (n = 10), cast nephropathy (n = 5), nodular glomerulosclerosis (n = 1), and mesangioproliferative glomerulonephritis with plasma cell infiltration (n = 1). Hypercalcemia (calcium 11-13.8 mg/dL) was the most common precipitating factor for acute renal failure. All 50 patients received combination chemotherapy of melphalan and prednisolone or vincristine, Adriamycin, and dexamethasone. More than half of the total number of patients did not complete chemotherapy because of death or lost to follow-up. Nineteen patients with acute renal failure and eight patients with chronic renal failure were treated with hemodialysis. Fourteen patients (28%) with acute renal failure had recovery of renal function. Twenty-three patients (46%) were lost to follow-up. Seven patients (14%) died from sepsis, uremia, or hyperkalemia. Remission of MM was found in 9 of 21 (42.8%) patients who completed chemotherapy. Thus, acute renal failure is the most common renal disease preceding the diagnosis of MM. Reversal of renal function is achieved with chemotherapy and hemodialysis treatment.
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PMID:Renal disease is a prodrome of multiple myeloma: an analysis of 50 patients from eastern India. 1946 74

The infiltration of nonmalignant cells surrounding the Reed-Sternberg cells within the tumors of Hodgkin lymphoma (HL) might be central to the pathophysiology of the disease. Severe sepsis results in a flood of cytokines that activate the immune system and is associated with generalized lymphocyte apoptosis. We report on 2 patients with HIV infection and HL who achieved durable complete remissions following only one cycle of chemotherapy that was complicated by neutropenic sepsis. An understanding of the pathophysiology of sepsis and immunologic activation that appear to have led to these long-term remissions might lead to novel therapeutic approaches for patients with HL.
Clin Lymphoma Myeloma 2009 Jun
PMID:Durable complete remissions in HIV-associated Hodgkin lymphoma after treatment with only one cycle of chemotherapy complicated by sepsis. 1952 96

Light chain deposition disease (LCDD) damages most frequently kidneys, and less frequently other organs. The incidence of LCDD is lower than the incidence of AL-amyloidosis. Symmetric swelling of both legs was the first sign of nephrotic syndrome with renal insufficiency in our female patient. Renal biopsy specimen revealed the diagnosis of LCDD. Bone marrow biopsy contained 40% of plasma cells. Bone survey showed no osteolytic changes. These findings confirmed the diagnosis of multiple myeloma (MM) Durie Salmon stage IB with LCDD. The patient was initially treated with 4 cycles of VAD (vinkristine, adriamycine, dexamethasone) chemotherapy with no response. Followed collection of peripheral haematopoietic stem cells and later high dose chemotherapy with reduced dose of melphalan 140 mg/sqm and autologous peripheral haematopoietic stem cells transplantation. Melphalan dose was reduced because of renal insufficiency (serum creatinine 290 micromol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 micromol/l. Worsening of renal function was most likely caused by nephrotoxicity of melphalan in nephrotic syndrome. This has been previously described in patients with AL-amyloidosis, and nephrotic syndrome who were treated with high dose melphalan. This phenomenon was entitled "post conditioning renal insufficiency". Hypoalbuminemia hypoproteinemia and reduced intravascular volume and renal damage caused by amyloid deposits as well as probably, amorphous non-amyloid deposits of monoclonal immunoglobulin are likely to have contributed to nephrotoxicity of the high dose of melphalan. However, worsening of renal insufficiency was facilitated by the mucositis-associated sepsis. Follow-up examination one month after high dose chemotherapy showed complete remission, that was confirmed by further examinations. In the course of the first year after high dose chemotherapy renal function gradually improved and nephrotic syndrome completely disappeared (complete kidney remission). Proteinuria declined to 2-3 g/24 hours and glomerular filtration slowly improved. Three years after high dose chemotherapy the patient is still in complete remission of multiple myeloma and free of nephrotic syndrome, with slightly increased creatinine (160 micromol/l) that, nevertheless, has had an improving tendency over last 3 years. The present case study illustrates accomplishment of complete haematological remission with high dose chemotherapy followed by autologous haematopoietic stem cells transplantation despite complete resistance of the disease to the standard chemotherapy VAD in a patient with MM and LCDD. We draw the reader's attention to the possibility of nephrotoxic effects of high dose melphalan (post conditioning renal insufficiency) in patients with nephrotic syndrome caused by light chain deposits as AL-amyloid or amorphous light chains deposits (LCDD)and we document the importance of plasma free light chain detection.
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PMID:[Complete remission of nephrotic syndrome and improvement of renal function in a patient with light chain deposition disease following high dose chemotherapy with transplantation of autologous haematopoietic stem cells. A case study and review of literature]. 2001 42

The aim of this study was to produce monoclonal and polyclonal antibodies against procalcitonin (PCT), a valid post-mortem marker of sepsis marker. Monoclonal antibodies (MAbs) were made from hyperimmune Balb/c mice by injecting 50 microg of purified antigen. These mice were immunized four times and given a final boost, and their spleen cells were collected and fused with SP2/0 myeloma cells under the presence of PEG 1450. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using purified protein. Lastly, five MAbs were obtained and designated successfully and were characterized by ELISA and Western immunoblotting. By Western immunoblotting, MAbs were found reactive with the patient's serum specifically. The results showed that the monoclonal antibodies could be used for various pathophysiological analyses in further investigations of procalcitonin and in preparing diagnostic kits.
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PMID:Targeting procalcitonin with novel murine monoclonal antibodies. 2056 91


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