Systemic immunoglobulin light-chain amyloidosis.
Amyloidosis is a rare disease in which amyloid fibrils compromise organ function and lead to death. Systemic immunoglobulin light-chain amyloidosis, usually caused by free light chains (FLCs) made by clonal plasma cells, is the most frequent type. Hereditary and senile systemic amyloidosis are less frequent types. Rarely, a patient with a tissue diagnosis of amyloidosis might have a monoclonal gammopathy and a hereditary protein. In systemic immunoglobulin light-chain amyloidosis, circulating clonal light chains can be measured with the FLC assay and provide a target for therapy aimed at eliminating the underlying plasma cell disorder while supporting the patient. Elimination of the pathologic FLC can lead to resorption of amyloid deposits and improvement in organ function. Monthly oral melphalan and dexamethasone for 1 year is effective therapy for patients not eligible for autologous stem cell transplantation (SCT) but carries a risk of myelodysplasia. For patients with limited organ involvement, SCT is an effective approach and, when followed after SCT by adjuvant thalidomide and dexamethasone for persistent plasma cell disease, achieves a high 1-year hematologic response rate. Complete hematologic responses can be durable beyond a decade and are usually associated with organ recovery. New agents, such as bortezomib and lenalidomide, have shown promising activity, and novel monoclonal antibody approaches are also under active investigation.
Comenzo
Raymond L
RL
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. comenzor@mskcc.org
D000686:Amyloidosis / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D003224:Congo Red / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D008854:Microscopy, Electron; D010265:Paraproteinemias / Q000628:therapy; D011228:Prealbumin / Q000235:genetics; D033581:Stem Cell Transplantation; D013997:Time Factors
D000970:Antineoplastic Agents; D007147:Immunoglobulin Light Chains; D011228:Prealbumin; D003224:Congo Red