New therapeutic approaches in primary systemic AL amyloidosis

Primary systemic AL (amyloid light-chain) amyloidosis is a plasma cell diso rder in which depositions of amyloid light-chain protein cause progressive organ failure. The prognosis of primary amyloidosis is generally poor, with a median survival of 1-2 years. There is no available treatment which impr oves impaired organ function by induction of amyloid mobilization. Since am yloidosis is a dynamic process, measures that reduce the supply of the amyl oid fibril precursor protein can result in a major regression of the deposi ts. Conventional-dose melphalan can prolong the median duration of survival from 8.5 to 18 months, but the clinical response rates with improvement of impaired organ function are low and the response is slow. Preliminary data suggest that VAD is effective in AL amyloidosis. Up-front high-dose chemot herapy with autologous peripheral blood stem cell transplantation can resul t in an improvement of the patient's clinical condition, but the treatment- related toxicity can be high, owing to impaired organ function. The use of VAD followed by high-dose chemotherapy is the concept of a German trial. Th e improvement of the patient's condition prior to high-dose chemotherapy by induction of a remission with VAD might reduce the transplantation-related morbidity and mortality in amyloidosis.