Amyloidosis is a group of disorders of varying etiology. The consistent pathologic event is the deposition of a characteristic insoluble protein in tissues and structures causing organ impairment. The most susceptible organs are the kidney, gastrointestinal tract, myocardium, and peripheral nerve. Amyloid is detectable by tissue biopsies where the characteristic apple-green fluorescence using the Congo red stain is seen. Rectal biopsies or subcutaneous fat biopsies have 80% to 90% sensitivity in confirming the presence of amyloid.

Primary amyloid is generally considered among the plasma cell dyscrasias, although an extremely low order of plasma cell proliferation is noted. Primary amyloid, or so-called AL amyloid. results from the deposition of immunoglobulin light chain in the susceptible organs. Secondary amyloid, also known as the AA type, is derived from “serum amyloid precursor protein” and is not associated with immunoglobulins. Secondary amyloid is associated with chronic conditions such as rheumatoid arthritis or chronic infections such as tuberculosis (TB).

Therapy for primary AL amyloid is generally directed at the presumed underlying lymphoproliferative cellular elements. Thus, melphalan and prednisone have been used most frequently. Unfortunately, response to therapy is difficult to follow because the total body burden of amyloid is unmeasurable.

In several studies from the Mayo Clinic, there appears to be an improvement in survival for those patients who take melphalan/prednisone versus placebo or colchicine. However, the studies have been complicated by design flaws and small numbers of patients. Most responses have been seen in patients with predominately renal, splenic, or hepatic involvement. The management of organ dysfunction remains important. Once patients develop symptomatic congestive heart failure, survival is poor. Those patients who have only a peripheral neuropathy have a median survival of more than 5 years.

Based on the success of high-dose strategies with the treatment of myeloma, high-dose strategies are also being applied to patients with amyloidosis. The initial results suggest that in selected patients there may be substantial benefit to this strategy.