Diagnosis and treatment of AL amyloidosis

AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which dep ositions of amyloid light-chain protein cause progressive organ failure. Vi rtually all patients with AL amyloidosis have a monoclonal protein in the s erum or urine or a monoclonal population of plasma cells in the bone marrow . The most common target organ is the kidney and renal amyloidosis manifest s as proteinuria or nephrotic syndrome in 3/4 of the patients. The median s urvival is one to two years. It is important to recognize that the amyloido sis is a dynamic process, and chemotherapy induced reduction of the activit y of the plasma cell clone reduces the supply of the amyloid precursor prot ein and can result in a major regression of the deposits. Amyloid-related n ephrotic syndrome and renal failure are potentially reversible. Conventiona l-dose melphalan as standard treatment can prolong the median duration of s urvival about 10 months, but the clinical response rates with improvement o f impaired organ function are low with a slow response. Upfront high-dose c hemotherapy with autologous peripheral blood stem cell transplantation is m uch more effective and can result in a major improvement of the patient's c linical condition, but the treatment-related toxicity can be relevant due t o impaired organ function. The initial use of a conventional-dose chemother apy consisting of vincristine, doxorubicin and dexamethasone (VAD) to achie ve a remission and subsequent high-dose chemotherapy is the concept of a Ge rman trial. The improvement of the condition of the patient by this approac h may increase the tolerability of high-dose chemotherapy and reduce transp lantation-related problems.