Current and emerging views and treatments of systemic immunoglobulin light-chain (Al) amyloidosis.
Amyloidosis is a disease in which abnormal proteins form toxic intermediates and fibrillar tissue-deposits that compromise key viscera and lead to early death. In order to treat amyloidosis, the type of abnormal protein must be identified. The most common type is monoclonal immunoglobulin light chain or AL amyloidosis. One-third to one-half of patients with systemic AL amyloidosis has renal involvement in the form of glomerular, vascular and interstitial deposits of amyloid causing progressive proteinuria. Less than 5% of AL patients present with renal failure requiring dialysis; patients with renal involvement usually present with fatigue, peripheral edema, proteinuria and hypoalbuminemia. The aim of therapy in systemic AL amyloidosis is to reduce the amyloid-forming monoclonal light chains, measured with the serum free light chain assay, by suppressing the underlying plasma cell dyscrasia, while using supportive measures to sustain organ function. Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor light chain is eliminated. The most effective treatment for systemic AL is risk-adapted melphalan with peripheral blood stem cell transplant; oral melphalan and dexamethasone is the most effective therapy for patients who are not stem cell transplant candidates although it carries a risk of myelodysplasia and leukemia. Novel therapies currently under study include thalidomide, bortezomib and lenalidomide. With therapy, a majority of patients can achieve long-term durable remissions with stabilization or recovery of organ function. The use of novel antibody-based approaches for imaging amyloid and possibly for accelerating removal of deposits is under active investigation.
Comenzo
Raymond L
RL
Cytotherapy Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. comenzor@mskcc.org
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000502:physiology*; D007155:Immunologic Factors / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016030:Kidney Transplantation; D008558:Melphalan / Q000627:therapeutic use
D000682:Amyloid; D018906:Antineoplastic Agents, Alkylating; D007147:Immunoglobulin Light Chains; D007155:Immunologic Factors; D008558:Melphalan