Summary of the EHA-ISA Working Group Guidelines for High-Dose Chemotherapy and Stem Cell Transplantation for Systemic AL Amyloidosis

The European Hematology Association (EHA) and International Society of Amyloidosis (ISA) recently agreed to collaborate on the development of guidelines for high-dose chemotherapy and stem cell transplantation (SCT) for the treatment of systemic light chain (AL) amyloidosis.1 A working group of key opinion experts of ISA was created, and the guidelines were developed and endorsed by the guidelines committee members of the EHA. The objectives were to provide healthcare professionals with clear guidance on the selection and management of patients with AL amyloidosis undergoing high-dose chemotherapy and SCT. Draft guideline was reviewed and agreed by the members of the writing group and approved by the board members of the ISA. The working group was chaired by Vaishali Sanchorawala, MD.

AL amyloidosis is usually caused by an indolent B-cell clone that produces an immunoglobulin light chain l in 75%-80% of cases and k light chains in the remaining cases. A high frequency (~40%-60%) of the chromosomal translocation t(11;14), which juxtaposes the immunoglobulin heavy chain locus (IgH) to the oncogene cyclin D1, characterizes this clone. Somatic mutations in IGLV (encoding the light chain variable region) reduce the fold stability of the native soluble protein and increase protein dynamics, which favors endoproteolysis and the production of soluble aggregates.