Blood Spotlight Systemic light chain amyloidosis: an update for treating physicians

The systemic amyloidoses comprise an increasing number of diseases characterized by multiorgan deposition of misfolded and aggregated autologous proteins as b-pleated sheet fibrils. Immunoglobulin light chain (AL) amyloidosis is the most common (incidence ;10 patients per million per year) and the most severe because it often targets the heart. A small, usually indolent plasma cell (PC) clone synthesizes an unstable, misfolded light chain (LC), which is prone to aggregate and form amyloid fibrils. This process causes systemic toxicity and devastating organ dysfunction. Genetic characteristics of amyloid LCs have been associated with kidney and heart predilection, but mechanisms of tissue specificity and organ dysfunction are poorly understood. Over the past decade, effective regimens have been developed markedly improving survival, but the 25% to 30% early death rate has not changed, with patients dying within a few weeks of cardiac failure due to late diagnosis. Early diagnosis remains the, as yet, elusive key for improving the care of this dreadful but treatable disease.