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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.
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PMID:AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma. 1207 17

AL amyloidosis complicating multiple myeloma is rare but well recognized. Endoscopic appearances of amyloid in the gastrointestinal tract can, however, be highly variable. Macroscopic appearances of the duodenum can range from scalloping (often seen in celiac disease) to that of duodenitis; erosive disease, frank ulceration and even protruberant masses. The importance of small bowel biopsies at the time of duodenal intubation and in gastroscopic examinations for iron deficiency anemia, must therefore be stressed.
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PMID:Iron-deficiency anemia complicating AL amyloidosis with recurrent small bowel pseudo-obstruction and hindgut sparing. 1208 40

Primary amyloid L chain (AL) amyloidosis is a plasma cell disorder in which depositions of AL cause progressive organ failure. The lack of effective therapies for this fatal disease prompts exploration of newer treatment avenues. We have investigated the application of antisense oligonucleotides (AS) for the inhibition of monoclonal Ig production. The monoclonal L chain was identified by using primers designed for amplifying the human lambda Ig V (Vlambda) region. We demonstrated that AS against L chain complementarity-determining regions inhibited the production of L chain in vitro. RPMI 8226 myeloma cells injected in SCID mice developed s.c. tumors. RT-PCR analysis showed Vlambda mRNA expression in the tumors. In addition, the presence of human Ig in the sera of mice given injection of RPMI 8226 cells was confirmed by ELISA. Administration of AS inhibited the expression of Vlambda mRNA in the s.c. tumors and decreased the concentration of L chain in serum. Therefore, we have shown that it is possible to determine the sequence of Vlambda mRNA and design specific complementary oligonucleotides, suggesting that treatment with Vlambda antisense could represent a rational novel approach to improve treatment outcome in AL amyloidosis.
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PMID:The antisense approach in amyloid light chain amyloidosis: identification of monoclonal Ig and inhibition of its production by antisense oligonucleotides in in vitro and in vivo models. 1224 7

High dose melphalan (HDM) followed by reinfusion of autologous blood stem cells (ASCT) has been applied in AL amyloidosis. Vincristine, doxorubicin, and dexamethasone (VAD) rapidly decrease light chain production in multiple myeloma. In a Phase I/II study of VAD followed by HDM and ASCT in AL amyloidosis, toxicity, feasibility, and response to this regimen were evaluated. Over a 5-year period 38 patients with AL amyloidosis were seen of which 12 out of 18 eligible patients participated in the study. VAD induced a distinct clonal response in 50% (6/12) of the patients, but without clinical improvement. In 11 patients HDM and ASCT was applied. Six months after ASCT 78% (7/9) of the surviving patients showed partial clonal response and none responded completely. Clinical condition evidently improved in 67% (6/9) of survivors, whereby clonal response, clinical response, performance score, and SAP scintigraphs were concordant. Therefore a complete clonal response is not a prerequisite for clinical improvement. With median follow-up after ASCT of 25 months, 75% of the study group patients were alive. Mortality was strongly depending on the number of organs involved Patients treated with HDM and ASCT had better survival than those not eligible (P < 0.0005).
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PMID:AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation. 1240 86

Amyloidosis is a heterogeneous group of extracellular protein deposition diseases. Age-related amyloidosis may be systemic or localized. The systemic forms include associated-myeloma AL amyloidosis and senile systemic amyloidosis which is the only clear-cut systemic form related to age and derived from normal transthyretin. In localized amyloidosis, the fibril protein precursors are synthesized in the tissue involved by the amyloid. In most cases, localized age-related amyloidosis does not appear to cause clinical disease with the exception of amyloid associated with Alzeihmer's disease and type 2 diabetes mellitus. The significance of aortic amyloidosis, amyloidosis of seminal vesicles, amyloid of the endocrine glands, and articular amyloidosis remains unknown.
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PMID:[Amyloidosis and aging]. 1248 87

Thalidomide is an effective therapy for multiple myeloma, although its mechanisms of action remain unclear. Light chain-associated (AL) amyloidosis is a plasma cell disorder related to multiple myeloma, but in AL amyloidosis, fibrillar tissue deposits of clonal immunoglobulin light chains produce organ dysfunction. To test the toxicity and efficacy of thalidomide in AL amyloidosis we initiated a phase I/II trial for patients with AL amyloidosis, most of whom had failed prior therapy with high-dose melphalan and autologous stem cell transplantation. This trial was designed as an individualized 6-month dose-escalation study with reevaluation of bone marrow plasmacytosis and serum and urine monoclonal proteins after 3 and 6 months. Sixteen patients were enrolled in the study with a median age of 62 years (range, 37-70 years). Fourteen patients had renal involvement, 4 had cardiac involvement, 4 had liver involvement, and 2 had predominant soft tissue or lymph node involvement. The median maximum tolerated dose was 300 mg, with fatigue and other central nervous system side effects being the major dose-limiting toxicities. Side effects not frequently reported for other patient populations included exacerbation of peripheral and pulmonary edema and worsening azotemia. In all, 50% of patients experienced grade 3/4 toxicity, and 25% had to discontinue the study drug. No complete hematologic responses were seen, but 25% of patients had a significant reduction in Bence-Jones proteinuria. Thus, while thalidomide has activity in AL amyloidosis, it also has significant toxicity in this patient population.
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PMID:Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. 1267 75

We report here a case of a 58-year-old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 microg/mL) in sera was within the normal range (0-8.0 microg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: kappa and lambda light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the lambda light chain, and negative for the amino terminus of constant region of the kappa light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow-up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.
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PMID:A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine. 1518 72

AL amyloidosis is a rare disorder characterised by tissue deposition of a fibrillary proteinaceous material, formed from monoclonal immunoglobulin light (or exceptionally heavy) chains. Although it may complicate multiple myeloma or B-cell lymphomas, AL amyloidosis is often associated with a low burden of clonal plasma cells ("primitive" AL amyloidosis). The mechanisms involved in the formation of AL amyloid deposits remain unclear, but are probably related to structural peculiarities of monoclonal immunoglobulin light chains. AL amyloidosis is usually a systemic disease, often revealed by renal involvement, the most common complication of the disease. The longterm prognosis of AL amyloidosis is poor, mainly related to amyloid restrictive cardiomyopathy leading to congestive heart failure. Oral melphalan and prednisone is considered the standard treatment for AL amyloidosis, but with limited increase in the median survival. High-dose intra-venous melphalan with autologous stem cell transplantation is an effective treatment, aimed at eliminating the clonaly expanded plasma cells, which has been shown to induce complete hematologic remissions and to prolong survival. However, the tolerability of such treatment is low, limiting its use to selected patients. The development of new drugs, able to interfere with amyloid fibril deposition, may provide a new therapeutic approach.
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PMID:[Immunoglobulin light chain amyloidosis: recent molecular, clinical and therapeutic approach]. 1529 Nov 38

The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis.
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PMID:Eosinophilia and symptomatic pulmonary amyloidosis. 1557 19

AL amyloidosis is the most common type of systemic amyloidosis in humans, and it is frequently associated with multiple myeloma. But, AL amyloidosis is very rare in domestic animals. A 16-year-old Quarter horse gelding was diagnosed with systemic AL amyloidosis associated with multiple myeloma. Clinical problems were rapid weight loss, muscle atrophy, soft unformed stool, and ventral edema. Grossly, diffuse gastrointestinal hemorrhage, markedly thickened jejunal mucosa, and splenomegaly were present. Microscopically, diffuse severe amyloid deposits were present in the lamina propria of glandular stomach, duodenum, and jejunum. Much of the spleen and sternal bone marrow was replaced by neoplastic round cells, and multiple foci of amyloid were also present in the spleen and bone marrow. Electron microscopy revealed the neoplastic round cells to be of plasma cell origin, and the amyloid showed a strongly positive immunoreactivity with polyclonal anti-human immunoglobin lambda light-chain antisera. To our knowledge, this is the second report describing systemic AL amyloidosis in domestic animals-associated plasma cell neoplasia and the first associated with multiple myeloma, as is common in humans.
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PMID:Systemic AL amyloidosis associated with multiple myeloma in a horse. 1565 77


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