Amyloidosis

Amyloidosis is a disease in which abnormal proteins form fibrillar tissue deposits that can 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; the other important type is hereditary, caused by variant forms of transthyretin and other proteins, whereas amyloid associated with chronic inflammation ("secondary") is rare in the developed world. AL can be misdiagnosed if a monoclonal gammopathy and a hereditary variant are present in the same patient. The aim of therapy in systemic AL amyloidosis is to reduce the amyloid-forming monoclonal light chain, 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 amyloidosis is risk-adapted melphalan with peripheral blood stem cell transplant (SCT). The hematologic response rate is 75% at 12 months when adjuvant therapy with thalidomide and dexamethasone is used post-SCT. Patients can achieve long-term durable remissions with organ recovery. Drugs effective in multiple myeloma are usually helpful in AL amyloidosis if tolerated. The use of novel antibody-based approaches for imaging amyloid and possibly for accelerating removal of deposits is under active investigation.