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)

Melphalan & Prednisone (MP) is considered as the standard therapy for Multiple Myeloma (MM) patients not eligible for high-dose therapy. Here, we report the results of a phase I-II study to evaluate the feasibility and efficacy of the association of PLD to the conventional MP regimen during the first six cycles of the front-line therapy for untreated MM patients older than 70. Thirty patients were included in the study with a median age of 77 years (71-84) and a M/F ratio of 17/13. The phase I of the study demonstrated that the maximum tolerable dose of PLD in this setting was 30 mg/m(2), so it was the final dose evaluated in the study. Twenty-nine patients were valuable for response, which was: complete in 4 (14%) partial in 15 (52%) minor/no changes in 7 (24%) and progressive in 3 (10%). The median progression free survival (PFS) was 24 months. The median overall survival (OS) has not been reached yet, with a 3-year probability for OS and PFS of 52 and 37%, respectively. Haematological toxicity was frequent but usually weak/moderate (grades 1 & 2 of the WHO scale) and it was resolved only with dose delays. Infection was a relatively frequent event (30% of patients), but only in 4 cases it was of grade 3. No cases of palmar-plantar erythrodysesthesia were observed. In conclusion, pegylated liposomal doxorubicin can be safely added to the other chemotherapeutic drugs in the treatment of elderly MM patients, which can be very useful for patients in whom novel agents are not tolerated or inefficient.
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PMID:Pegylated liposomal doxorubicin, melphalan and prednisone therapy for elderly patients with multiple myeloma. 1700 69

End-organ damage is the factor that differentiates plasma cell dyscrasia requiring therapy (active multiple myeloma [MM]) from disease that does not require therapy (monoclonal gammopathy of undetermined significance and smoldering [asymptomatic] MM). Progressive skeletal destruction is the hallmark of MM and responsible for principle morbidity in the disease. The spine is the most afflicted skeletal organ, and vertebral fractures have significantly contributed to its poor prognosis. Early mortality in MM is usually attributed to the combined effects of active disease and comorbid factors. Infection and renal failure are the main direct causes of early mortality. Using bisphosphonates to manage skeletal events mainly by preventing or slowing the destructive process has become an important adjunctive treatment in MM. Advances in minimally invasive surgical techniques, such as percutaneous vertebroplasty and kyphoplasty, offer these patients less-invasive options for treating vertebral collapse and restoring function. The aggressive management of other complications of the disease through more effective and less toxic therapy that targets the primary disease, in addition to supportive care, is resulting in patients experiencing less morbidity and probably lower mortality. This article reviews recent advances in the understanding of bone disease in MM, the role of bisphosphonates in preventing skeletal events, and available data on percutaneous vertebroplasty and kyphoplasty, and discusses the management of infection and renal failure, which seem to be responsible for high initial mortality and thereby compromise the current advances in therapy.
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PMID:Multiple myeloma: most common end-organ damage and management. 1733 86

Ecthyma gangrenosum (EG) is considered to be a pathognomonic sign of Pseudomonas aeruginosa septicemia and is predominantly seen in immunosuppressed patients. Although P. aeruginosa is the most recognized pathogen of EG, numerous other organisms have been reported to cause clinically identical lesions. We report a case of an EG-like eruption caused by Burkholderia cepacia, in an intensive care unit patient with multiple myeloma.
Infection 2008 Jun
PMID:Burkholderia cepacia as a cause of ecthyma gangrenosum-like lesion. 1796 3

In myeloma bone disease, bisphosphonates have been shown to delay the progression of osteolytic lesions and prevent fractures. In the case of painful vertebral fractures, vertebroplasty and kyphoplasty have become standard procedures to control symptoms and restore the original height of the vertebrae. Adequate pain control is of crucial importance for the quality of life of myeloma patients, as is maintaining adequate hemoglobin levels with the use of erythropoietic growth factors. Infections should be treated aggressively in myeloma patients, as these contribute significantly to morbidity and mortality. In patients with repeated infectious complications, prophylactic measures such as long-term application of antibiotic or antiviral medication or use of intravenous immunoglobulins is recommended. The concerted action of these supportive therapies can significantly improve the wellbeing of myeloma patients in phases of disease progression as well as during phases of remission. In progressive disease, certain measures such as adequate pain control and radiotherapy can ameliorate symptoms until the therapeutic effect of systemic anti-neoplastic therapy becomes evident.
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PMID:Supportive care in multiple myeloma. 1807 Jul 21

Osteonecrosis of the jaw (ONJ) was first reported in the dental literature in 2003. The term was coined to describe a spectrum of dental problems seen in cancer patients treated with high doses of intravenous bisphosphonates for the prevention of skeletal-related events. By consensus, the syndrome is now defined by the presence of exposed bone in the mouth which fails to heal after appropriate intervention over a period of 6 or 8 weeks. It is most common in patients with breast or prostate cancers, or multiple myeloma treated with bisphosphonates, of whom about 5% develop the condition. In patients receiving the much lower drug doses used in osteoporosis, the incidence appears to be approximately 1/100,000 patient-years, probably comparable to that in the general population. It is likely that ONJ results from direct drug toxicity to cells of bone and soft tissue. The bone in ONJ lesions does not appear to be 'frozen' but rather there is very active bone resorption taking place, which is likely to be responsible for the local release at high concentrations of bisphosphonates. Infection probably plays a pivotal role in driving this resorption, so its active management is critical. Obvious abnormalities are apparent with a variety of radiologic modalities, and it is not clear that radiographs are inferior to other approaches. Most authors favor a conservative approach to surgical debridement of the lesions.
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PMID:Osteonecrosis of the jaw. 1864 76

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

The proteasome, a multicatalytic protease, is responsible for the generation of most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. In the present study, we investigated the effect of bortezomib on viral infection. Infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus (LCMV) led to a decreased cytotoxic T cell response to several LCMV-derived CD8(+) T cell epitopes. Bortezomib treatment caused a reduced expansion of CD8(+) T lymphocytes and increased viral titers in LCMV-infected mice. Administration of bortezomib during expansion of CD8(+) T cells had no influence on the cytotoxic T cell response, suggesting that bortezomib interferes with priming of naive T cells. Indeed, determination of Ag load in spleen 4 days post infection, revealed a reduced presentation of LCMV-derived cytotoxic T cell epitopes on MHC class I molecules. In summary, we show that proteasome inhibition with bortezomib led to an increased susceptibility to viral infection, and demonstrate for the first time, that proteasome inhibitors can alter Ag processing in vivo.
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PMID:The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. 1984 Nov 90

Infections continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), as therapeutic advances have occurred over the past several decades. The pathogenesis of infection in these patients is multifactorial, including inherent immune defects related to the primary disease process, such as hypogammaglobulinemia, as well as therapy-related immunosuppression. A characteristic spectrum of infectious complications has been described for specific treatment agents. With chlorambucil, most infections are bacterial in origin, caused by common Gram-positive and -negative organisms. Recurrent infections are a hallmark, with the respiratory tract being the most common site of infection. The pathogenesis of infection with the purine analogues is related to the quantitative and qualitative T-cell abnormalities induced by these agents. Risk factors for infection identified in patients treated with fludarabine include advanced-stage disease, prior CLL therapy, response to therapy, elevated serum creatinine, hemoglobin < 12 g/dL, and decreased serum IgG. As compared with patients receiving chlorambucil, patients receiving fludarabine have more major infections and herpes virus infections. However, Pneumocystis, Aspergillus, and cytomegalovirus (CMV) infections are uncommon. The use of alemtuzumab is complicated by frequent opportunistic infections. CMV reactivation is especially problematic, occurring in 10%-25% of patients. For prevention of infection, the use of vaccinations and immunoglobulin replacement has been studied. Recommendations for prophylactic antimicrobial therapy have arisen from CLL treatment trials and anecdotal reports. As new treatment approaches are developed for CLL, one must consider not only the efficacy of these agents for disease response but also the effect on subsequent infectious complications. Infectious complications remain a significant cause of morbidity and mortality in patients with CLL. We will review the pathogenesis as well as the spectrum of infections in these patients. We will also discuss approaches to the prophylactic and therapeutic management of infections in these patients.
Clin Lymphoma Myeloma 2009 Oct
PMID:Infectious complications in patients with chronic lymphocytic leukemia: pathogenesis, spectrum of infection, and approaches to prophylaxis. 1985 55

Patients with multiple myeloma (MM) have a high rate of infectious complications and symptomatic anemia. Emerging antineoplastic therapies are resulting in a better response, but still quality of life and potentially survival can be significantly affected by these complications. Multiple cytokines and an impaired immunologic system are involved in the development of these complications. Emerging therapies and guidelines will be reviewed taking in consideration the benefits versus risks of those strategies. The beneficial effect of recombinant human erythropoietin (EPO) and darbepoietin alpha in MM patients have been confirmed in several trials. Evidenced-based guidelines for the use of EPO in patients with cancer should be closely followed to ensure correct use of erythropoiesis stimulating agents. Infection, despite being the most common cause of morbidity and mortality, can be controlled by prompt recognition and proper prophylaxis.Supportive care is an important adjunct to cancer therapy. Adequate use of pharmacologic strategies to control anemia and prevent or treat infectious complications will result in benefit to MM patients.
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PMID:Anemia and infections in multiple myeloma: supportive therapy. 1995 2

The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 months, P = 0.071), and progression-free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3-year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3-4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results.
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PMID:Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. 2064 30


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