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)

Primary (AL) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in major organs, such as the kidneys, heart, and bowel. Organ dysfunction contributes to a high mortality and poor prognosis, with a median survival time of 1-2 years from diagnosis. Here, we present a 46-year-old man with an exceptional clinical course of an LC multiple myeloma with generalized amyloidosis, causing renal insufficiency, congestive heart failure, and complete intestinal necrosis. We have summarized recent knowledge on AL amyloidosis, its association with monoclonal gammopathies, clinical presentations, diagnostic tools, and treatment strategies. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL amyloidosis. This may facilitate earlier diagnosis, and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis.
 ...
PMID:Primary (AL) amyloidosis in plasma cell disorders. 1688 Feb 41

In immunoglobulin light chain (AL) amyloidosis, amyloid fibril deposits derived from immunoglobulin light chains produced by a clonal plasma cell dyscrasia accumulate in tissues and damage vital organs. Treatment regimens used in multiple myeloma can be effective in AL amyloidosis; however, patients with this disease often tolerate these regimens poorly because of multisystem organ dysfunction. Thalidomide and lenalidomide have both been shown to be effective in myeloma. In this report, we describe results of a phase 2 trial of the use of lenalidomide, as a single agent and in combination with dexamethasone, for the treatment of AL amyloidosis. Thirty-four patients with AL amyloidosis, most with prior therapies, were enrolled in the trial. The initial dose of lenalidomide used (25 mg/d) was poorly tolerated; however, a reduced dose of 15 mg/d was generally well tolerated. Of 24 evaluable patients, 7 (29%) achieved a hematologic complete response and 9 (38%) achieved a partial hematologic response, for an overall hematologic response rate of 67%. Hematologic responses were also associated with clinical responses. Fatigue and myelosuppression were the most common treatment-related adverse events (35%), while thromboembolic complications (9%) were the most serious. Findings from this trial indicate that lenalidomide can be effective in treating AL amyloidosis.
 ...
PMID:Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. 2084 11

A 48-year-old male patient presented with dyspnea on exertion. Patient was found to have pulmonary hypertension. Myocardial biopsy showed amyloidosis and further work-up revealed Salmon-Durie stage 1A multiple myeloma. Patient had no other clinical manifestations of amyloidosis. It is possible that the pulmonary hypertension is caused by amyloid deposition into pulmonary arteries as the arterial amyloid deposition is common in AL amyloidosis. Treatment with sildenafil led to hemodynamic and symptomatic improvement.
 ...
PMID:Pulmonary hypertension as a dominant clinical picture in a case of amyloidosis and smoldering multiple myeloma. 1704 43

Primary amyloidosis is a plasma cell dyscrasia characterised by excess production of abnormal immunoglobulin light chains with their subsequent accumulation in kidneys, heart, liver as well as gastrointestinal tract and bone marrow 1-21, 2. These tissue deposits take the form of a fibrillar protein which damages the involved organ in proportion to the extent of the infiltration and roughly parallels the duration of the disease. Most cases have evidence of the underlying lymphoplasmacytoid neoplasm recognisable in two ways. Firstly, the monoclone appears in the serum [2]. Secondly is a morphologically and immunohistochemically distinctive cellular infiltrate in the bone marrow [3] that has a specific microscopic and ultrastructural pattern 4-54, 5. Interestingly occasional patients, who survive long enough, may progress to multiple myeloma [6] but the correlation is variable [7].
 ...
PMID:Amyloidosis: a changing clinical perspective. 1745 99

AL amyloidosis is a disease in which immunoglobulin L chain is deposited in multiple organs, and the prognosis of cardiac amyloidosis is extremely poor. Although several treatments based on that for multiple myeloma, have been performed, there is no clear evidence that cardiac function is improved. We report a case of AL cardiac amyloidosis with moderate cardiac dysfunction for which we performed autologous peripheral blood stem cell transplantation (auto-PBSCT) in combination with high-dose melphalan therapy. This treatment resulted in significant improvement in cardiac function and good prognosis for about 3.5 years after the diagnosis. Therefore, auto-PBSCT is a possible option as up-front therapy for AL cardiac amyloidosis.
 ...
PMID:Improvement of cardiac diastolic function and prognosis after autologous peripheral blood stem cell transplantation in AL cardiac amyloidosis. 1793 25

The automated quantification of serum free kappa and lambda light chain concentrations provides a highly sensitive tool for the diagnosis and monitoring of monoclonal gammopathies. An abnormal kappa:lambda ratio supports the presence of clonal plasma cell expansion and requires further investigation. More than 94% of myeloma, light chain myeloma, and AL amyloidosis and, likewise, a majority of patients with light chain deposition disease are detectable with this technology. Importantly, these assays identify M-proteins in most patients with oligosecretory disease and permit their recruitment into clinical trials from which they have been previously excluded. Combining serum free light chain testing with traditional electrophoresis provides > 99% accuracy in the first-line diagnosis of monoclonal gammopathies and eliminates the need for urine testing in most instances. One third of patients with monoclonal gammopathy of undetermined significance have an abnormal free light chain ratio, and these patients harbor a greater risk of progression to plasma cell dyscrasia. For monitoring response to therapy, the international uniform response criteria define a normal free light chain ratio as an essential element of the "stringent complete response" category. Because the half-life of free light chains is < 6 hours, free light chain measurements at short sampling intervals allow real-time measurement of treatment-induced tumor kill, and provide prompt indications of chemosensitivity, dose adequacy, need for alternative approaches, and even prognosis, as demonstrated in AL amyloidosis if the involved free light chain concentration normalizes. Clinical applications of these assays will likely increase as their utility is more widely explored.
Clin Lymphoma Myeloma 2007 Sep
PMID:Value of serum free light chain testing for the diagnosis and monitoring of monoclonal gammopathies in hematology. 1802 69

Renal involvement is common in multiple myeloma. Although several types of renal disease are observed, most of them are considered to be specifically related to monoclonal immunoglobulin light chains. Myeloma cast nephropathy is the most frequent and sometimes associated with acute renal failure. AL amyloidosis and monoclonal immunoglobulin deposit disease are often presented as a nephrotic syndrome. In this review, we describe the pathogenesis and diagnosis of these three renal diseases. We also focus on the treatment of renal disease in multiple myeloma, in the view points of the chemotherapy to reduce M-protein and the prevention to reduce the risks of promoting renal injury.
 ...
PMID:[Renal disease in multiple myeloma]. 1806 65

Amyloidosis is characterized by extracellular deposition of abnormal protein. There are six types: primary, secondary, hemodialysis-related, hereditary, senile, and localized. Primary (AL) amyloidosis is associated with monoclonal light chains in serum and/or urine with 15% of patients having multiple myeloma. Secondary (AA) amyloidosis is associated with inflammatory, infectious, and neoplastic diseases. The presentation is protean, including macroglossia, a dilated and atonic esophagus, gastric polyps or enlarged folds, and luminal narrowing or ulceration of the colon. Amyloid deposition in the gastrointestinal (GI) tract is greatest in the small intestine. The symptoms include diarrhea, steatorrhea, or constipation. Pseudo-obstruction carries a particularly grave prognosis, often not responding to pro-motility agents. Hepatic involvement is common, but the clinical manifestations are usually mild with hepatomegaly and an elevated alkaline phosphatase level. Biopsies to diagnose amyloidosis can be taken from the fat, kidney, intestine, or bone marrow. The safety of liver biopsies is controversial. With Congo Red stain, amyloid appears red in normal light and apple-green in polarized light. Treatment for AL amyloidosis is chemotherapy and stem cell transplantation; treatment for AA amyloidosis is control of the underlying disease. Amyloidosis should be considered in patients with proteinuria, cardiomyopathy, hepatomegaly (with mildly abnormal liver tests), peripheral and autonomic neuropathy, weight loss, and GI symptoms.
 ...
PMID:Gastrointestinal manifestations of amyloidosis. 1972 11

Amyloidosis is a rare systemic disorder of protein metabolism with progressive extra-cellular deposition of insoluble fibrillary protein, disorganization of tissue architecture, and subsequent organ dysfunction. Primary amyloidosis is the most common form of this disorder, however, it can develop secondary to plasma cell dyscrasias such as multiple myeloma (MM); 10-15% of MM patients may develop amyloidosis of vital organs. Amyloidosis is usually associated with bleeding, but less commonly with thrombosis. We present a 52-year-old Saudi female with amyloidosis secondary to multiple myeloma. She presented with both venous and extensive arterial thrombosis. Although relatively rare, plasma cell dyscrasias such as amyloidosis and multiple myeloma could present with thrombotic rather than hemorrhagic complications.
 ...
PMID:Amyloidosis and vascular thrombosis. 1808 44

In the last decade, laboratory diagnostics of monoclonal gammopathies has taken a huge step forward. The study takes a brief look at the methods currently being used, discussing their significance, the problems faced in their definition and interpretation. Among the primary clinical-biochemical methods, there are agarose electrophoresis and capillary electrophoresis. Immunofixation electrophoresis has completely replaced immunoelectrophoresis in determining immunoglobin classes and antigen types of paraprotein light chains. Immunofixation is more sensitive and quicker. The determining of the concentration of free light chains (non-secretory myeloma, AL amyloidosis, illness from light chains) has also found its place in the algorithm of laboratory methods used in monoclonal gammopathy. Out of the many prognostic factors, the combination beta2-microglobulin and albumin has been chosen as the easiest and the one with the highest informative value. The spectrum of laboratory examinations is completed by determining the viscosity of serum and identification of cryoglobulins.
 ...
PMID:[Laboratory identification of monoclonal immunoglobin]. 1818 Dec 83


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