What does AL (Amyloid Light-chain) amyloidosis stand for in a middle-aged to older adult patient?

What AL Amyloidosis Stands For

AL amyloidosis stands for Amyloid Light-chain amyloidosis, also previously known as "primary" amyloidosis, and represents a plasma cell disorder where monoclonal immunoglobulin light chains misfold and deposit as amyloid fibrils in organs. 1

Definition and Nomenclature

The "AL" designation specifically refers to:

• A = Amyloid (the fibrous protein deposits)
• L = Light chain (the immunoglobulin light chain protein that forms the amyloid) 1

The term "light chain amyloidosis" reflects the underlying pathophysiology where unstable immunoglobulin free light chains (FLCs) are secreted by a clonal plasma cell population in the bone marrow 1

Pathophysiologic Basis

The disease mechanism involves:

• A small, slowly proliferating bone marrow plasma cell clone produces excessive monoclonal immunoglobulin light chains 1
• These light chains fail to pair with heavy chains to form stable heterotetramers 2
• The unpaired light chains are inherently unstable and undergo misfolding 2, 3
• Lambda (λ) light chains are involved in 75-80% of cases, with kappa (κ) in the remaining cases 1, 4
• The misfolded proteins form amyloid fibrils that deposit extracellularly in various organs 1, 5

Clinical Distinction from Other Amyloidoses

AL amyloidosis must be distinguished from other systemic amyloidoses:

• ATTR amyloidosis involves transthyretin protein (either hereditary or wild-type/senile) 1, 6
• AA amyloidosis (secondary amyloidosis) results from deposition of amyloid A protein in chronic inflammatory conditions 1, 4
• AL is the most common form of systemic amyloidosis, affecting approximately 10 per million per year 1

Organ Involvement Pattern

AL amyloidosis characteristically affects:

• Heart and kidneys are the two most frequently involved organs 1
• Over 69% of patients have more than one organ involved at diagnosis 1
• Other commonly affected sites include gastrointestinal tract, liver, peripheral and autonomic nervous systems, and soft tissues 1
• Cardiac involvement is the main driver of prognosis and mortality 1

Association with Multiple Myeloma

The relationship between AL amyloidosis and multiple myeloma:

• Approximately 10-15% of multiple myeloma patients also have AL amyloidosis 1
• Conversely, 10% of AL amyloidosis cases are associated with multiple myeloma 1
• Both represent clonal plasma cell expansions, but the plasma cell burden is generally higher in multiple myeloma 1