How We Manage Systemic Immunoglobulin Heavy Chain Amyloidosis (AH Amyloidosis) and Immunoglobulin Heavy-and-Light-Chain Amyloidosis (AH/AL Amyloidosis)

Clinical Practice Points•Immunoglobulin heavy chain amyloidosis (AH amyloidosis) and immunoglobulin heavy-and-light-chain amyloidosis (AH/AL amyloidosis) are extremely rare subtypes of immunoglobulin-derived amyloidosis. There is limited literature on how to diagnose and manage these disorders.•We describe two cases: an AH case managed with autologous hematopoietic stem-cell transplantation (HSCT), and an AH/AL case managed with daratumumab-based therapy provided as a salvage regimen with good outcome.•Utilizing HSCT for eligible patients and incorporating daratumumab-based therapy for HSCT-ineligible patients can provide excellent response with acceptable tolerability.•Immunofluorescence performs worse than laser microdissection/mass spectrometry when typing immunoglobulin-derived amyloidosis. Therefore, complementing immunofluorescence with mass spectrometry when available can be helpful when typing challenging cases of immunoglobulin-derived amyloidosis. •Immunoglobulin heavy chain amyloidosis (AH amyloidosis) and immunoglobulin heavy-and-light-chain amyloidosis (AH/AL amyloidosis) are extremely rare subtypes of immunoglobulin-derived amyloidosis. There is limited literature on how to diagnose and manage these disorders.•We describe two cases: an AH case managed with autologous hematopoietic stem-cell transplantation (HSCT), and an AH/AL case managed with daratumumab-based therapy provided as a salvage regimen with good outcome.•Utilizing HSCT for eligible patients and incorporating daratumumab-based therapy for HSCT-ineligible patients can provide excellent response with acceptable tolerability.•Immunofluorescence performs worse than laser microdissection/mass spectrometry when typing immunoglobulin-derived amyloidosis. Therefore, complementing immunofluorescence with mass spectrometry when available can be helpful when typing challenging cases of immunoglobulin-derived amyloidosis.