{"doi":"10.3390/jcm14124146","title":"Screening for Systemic Light-Chain Amyloidosis in Patients Over 60 with λ Monoclonal Gammopathies","abstract":"Background/Objectives: To reduce the early mortality of light-chain amyloidosis (AL), earlier diagnosis is needed. To pursue this goal, we conducted a multicenter study screening for AL λ-type (NCT04615572) in subjects > 60 years of age with λ smoldering myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), a light-chain differential (dFLC, λ minus κ) > 23 mg/L, and no prior amyloid diagnosis. Methods: Variables included AL-related IGVL gene usage and clonal plasma cell cytogenetic abnormalities, such as t(11;14) or gain 1q, which are present in 75% of AL cases. Here, 9 out of 33 λ IGVL genes, accounting for 90% of AL λ cases, were considered to be AL-related. Bone marrow was obtained, plasma cell cytogenetics and next generation sequencing for IGVL genes were performed, and subjects with AL-related IGVL genes were screened for AL using tissue studies. Results: From 2021 to 2023, we enrolled 30 subjects (19 M/11 F) with a median age of 68.5 years old (IQR 64.3–73), 17 SMM and 13 MGUS, with a median of 6% marrow plasma cells (range, 3.5–40). Here, 11 SMM and 4 MGUS cases had t(11;14) or gain 1q; 10/17 SMM and 12/13 MGUS had AL-related genes, and AL was ultimately confirmed by tissue biopsy in 3 with SMM. SMM, AL-related IGVL genes, and t(11;14) or gain 1q were found in 6 SMM subjects, including the 3 with AL (3/6 vs. 0/16; p < 0.05, Fisher’s exact, two-tailed). Conclusions: These results justify a larger study screening for AL in SMM to develop a likelihood algorithm for AL using dFLC, IGVL gene usage, and the presence of t(11;14) or gain 1q.","journal":"Journal of Clinical Medicine","year":2025,"id":544735,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":421808,"name":"Mahesh Mansukhani","orcid":"0000-0003-2044-0751","position":1,"is_corresponding":false},{"id":555075,"name":"Raymond T. Yeh","orcid":null,"position":2,"is_corresponding":false},{"id":1302335,"name":"Jiesheng Lu","orcid":null,"position":3,"is_corresponding":false},{"id":1302336,"name":"Hongai Xia","orcid":null,"position":4,"is_corresponding":false},{"id":1265473,"name":"Lahari Koganti","orcid":null,"position":5,"is_corresponding":false},{"id":1302337,"name":"Jiuhong Pang","orcid":null,"position":6,"is_corresponding":false},{"id":1301915,"name":"Denis Toskic","orcid":"0000-0002-3340-762X","position":7,"is_corresponding":false},{"id":290360,"name":"Stephanie Scalia","orcid":null,"position":8,"is_corresponding":false},{"id":1123977,"name":"Xun Ma","orcid":null,"position":9,"is_corresponding":false},{"id":834521,"name":"Lisa X. Lee","orcid":"0000-0002-0664-2253","position":10,"is_corresponding":false},{"id":356529,"name":"Sandy W. Wong","orcid":"0000-0003-1046-1807","position":11,"is_corresponding":false},{"id":1435245,"name":"Alfred Chung","orcid":"0000-0003-0196-5456","position":12,"is_corresponding":false},{"id":382455,"name":"Sascha A. Tuchman","orcid":"0000-0003-2109-1573","position":13,"is_corresponding":false},{"id":1435644,"name":"Terry Fogaren","orcid":null,"position":14,"is_corresponding":false},{"id":1302338,"name":"Nancy Coady Lyons","orcid":null,"position":15,"is_corresponding":false},{"id":1297225,"name":"Cindy Varga","orcid":"0000-0003-4882-5581","position":16,"is_corresponding":false},{"id":407168,"name":"Suzanne Lentzsch","orcid":"0000-0003-1708-7344","position":17,"is_corresponding":false},{"id":600813,"name":"Raymond L. Comenzo","orcid":"0000-0002-6255-5824","position":18,"is_corresponding":false},{"id":1301914,"name":"Ping Zhou","orcid":"0000-0002-4496-4085","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40565890","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}