Novel approaches to the treatment of primary amyloidosis

Primary (AL, amyloid light-chain) amyloidosis is a plasma cell disorder in which deposits of amyloid light-chain protein cause progressive organ failu re. It is important to recognise that amyloidosis is a dynamic process and chemotherapy-induced reduction of the activity of the plasma cell clone red uces the supply of the amyloid precursor protein and can result in a major regression of the deposits. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome. Proteinur ia is seen in three quarters of patients. Amyloid related nephrotic syndrom e and renal failure are potentially reversible. Fatigue, congestive heart f ailure, hepatomegaly, peripheral neuropathy, orthostatic hypotension, carpa l tunnel syndrome and macroglossia are other common features. The median su rvival is one to two years. Conventional-dose melphalan as standard treatme nt can prolong the median duration of survival by about ten months, but the clinical response rates with improvement of impaired organ function are lo w. Up-front high-dose chemotherapy with autologous peripheral blood stem ce ll transplantation is much more effective and can result in a major improve ment in the clinical condition of patients. However, the toxicity related t o this treatment can be relevant due to impaired organ function. Convention al-dose chemotherapy consisting of vincristine, doxorubicin and dexamethaso ne or high-dose dexamethasone or interferon-alpha are other possible approa ches to treatment. The improvement of patient condition with an effective c onventional-dose chemotherapy may increase the tolerability of high-dose ch emotherapy and reduce transplantation related problems.