In a study reported in the British Journal of Haematology, Staron et al found that the prevalence of plasma cell and lymphoproliferative disorders among blood relatives of probands with light chain (AL) amyloidosis was low overall and varied according to proband AL amyloidosis subtype. Despite congruence of light chain isotypes in affected families, there was no apparent correlation with organ involvement.
The study involved data on 1,621 patients in the prospectively maintained database at the Boston University Amyloidosis Center diagnosed with systemic or localized AL amyloidosis between 2000 and 2021 who had family history information available.
Key Findings
Among the 1,621 patients, a total of 44 probands (2.7%) were identified, with 52 relatives affected. The number of probands was:
- 30 (2.7%) among 1,103 patients with systemic AL amyloidosis (36 affected relatives)
- 5 (4.5%) among 110 with multiple myeloma–associated AL amyloidosis (6 affected relatives)
- 4 (6.0%) among 67 with lymphoplasmacytic lymphoma–associated AL amyloidosis (4 affected relatives)
- 5 (1.5%) among 341 with localized AL amyloidosis (6 affected relatives).
The most common plasma cell and lymphoproliferative disorders in family members were multiple myeloma (n = 26, 48%) and AL amyloidosis (n = 9, 18%), followed by monoclonal gammopathy of undetermined significance (n= 6, 12%), non-Hodgkin lymphoma (n = 5, 10%), lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia (n = 4, 8%), and chronic lymphocytic leukemia (n = 3, 6%).
The isotype of the clonal immunoglobulin was known for both members in a subset of families; in these kinships, there was 100% congruency in light chain isotype among relatives. Despite the congruence of light chain isotypes, there was no apparent correlation in organ involvement between members of families with multiple cases of systemic AL amyloidosis. For example, among six individuals from three families, only 4 of 10 affected organs were overlapping.
The investigators concluded, “[We] described familial aggregations of plasma cell and lymphoproliferative disorders in systemic and localized AL amyloidosis. These findings help generate hypotheses about familial influences in AL amyloidosis. Directions for future research include sequencing of germline light chain variable region genes and running genome-wide association studies to look for shared mutations in familial cases.”
Vaishali Sanchorawala, MD, of the Amyloidosis Center, Boston University School of Medicine, is the corresponding author for the British Journal of Haematology article.
Disclosure: The Amyloidosis Center database is supported by the Amyloid Research Fund of Boston University School of Medicine. For full disclosures of the study authors, visit onlinelibrary.wiley.com.
