Serum Free Light Chains in Lymphoma: A Phenotype-First Framework for Biological Interpretation, Analytical Control, and Clinical Use.
- 1National Institute for Infectious Diseases, "Lazzaro Spallanzani," IRCCS, Via Portuense 292, 00149 Rome, Italy.
- 2Blue Wave Therapeutics GmbH, Kreuzstrasse 4, CH-4123 Allschwil, Switzerland.
Abstract
Serum free light chains (sFLC) reflect immunoglobulin production and renal clearance, making abnormal results biologically heterogeneous in lymphoma. We reviewed clinical, translational, and analytical evidence using a documented PubMed search. Three operational patterns should be distinguished: monoclonal-pattern elevation, polyclonal-pattern elevation, and ratio-only abnormality. The kappa-plus-lambda concentration is an overlapping measure of total circulating burden rather than a fourth exclusive phenotype. In diffuse large B-cell lymphoma, some cohorts reported International Prognostic Index-adjusted associations and improved model discrimination, whereas other studies did not confirm independent prognostic value. Evidence in classical Hodgkin lymphoma and chronic lymphocytic leukemia also depends on endpoint, adjustment, and treatment setting. Prediagnostic associations in human immunodeficiency virus infection, transplantation, and population cohorts do not establish screening utility. In Waldenström macroglobulinemia, involved-chain kinetics may supplement established assessment in selected patients, although clinical benefit from sFLC-directed management has not been demonstrated. Historical treatment regimens, overlapping cohorts, inconsistent renal adjustment, assay differences, and limited external validation restrict transferability. The proposed framework integrates phenotype, renal function, assay, sampling time, and disease context. It is an interpretive proposal, not a validated prognostic score or treatment algorithm.
Related
- Analytical and Biological Factors Associated with Oncogenic Variant Yield in Tumor-Agnostic Plasma ctDNA Profiling
- Case Report: Suspected biventricular arrhythmogenic cardiomyopathy presenting as a dilated cardiomyopathy-like phenotype with multimodal phenotyping and cautious genetic interpretation
- HbA1c and skeletal muscle health in type 2 diabetes: phenotype-specific associations across different analytical directions and mechanistic insights
- Circulating tumor DNA in Hodgkin lymphoma: biological classification, molecular residual disease, and integration with PET response
- Clinical and Biological Correlates of Resistance and Relapse After CD19-Directed CAR T-Cell Therapy in Large B-Cell Lymphoma: A Structured Narrative Review
BibTeX
@article{bibas2026serum,
title = {{Serum Free Light Chains in Lymphoma: A Phenotype-First Framework for Biological Interpretation, Analytical Control, and Clinical Use.}},
author = {Michele Bibas and Barbara Amoroso and Elena Matteini and Andrea Antinori and Valentina Mazzotta},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = sep,
doi = {10.3390/curroncol33100580},
url = {https://europepmc.org/article/MED/42930147},
note = {CC BY},
}
RIS
TY - JOUR
TI - Serum Free Light Chains in Lymphoma: A Phenotype-First Framework for Biological Interpretation, Analytical Control, and Clinical Use.
AU - Michele Bibas
AU - Barbara Amoroso
AU - Elena Matteini
AU - Andrea Antinori
AU - Valentina Mazzotta
PY - 2026
DA - 2026/09/28
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100580
UR - https://europepmc.org/article/MED/42930147
AB - Serum free light chains (sFLC) reflect immunoglobulin production and renal clearance, making abnormal results biologically heterogeneous in lymphoma. We reviewed clinical, translational, and analytical evidence using a documented PubMed search. Three operational patterns should be distinguished: monoclonal-pattern elevation, polyclonal-pattern elevation, and ratio-only abnormality. The kappa-plus-lambda concentration is an overlapping measure of total circulating burden rather than a fourth exclusive phenotype. In diffuse large B-cell lymphoma, some cohorts reported International Prognostic Index-adjusted associations and improved model discrimination, whereas other studies did not confirm independent prognostic value. Evidence in classical Hodgkin lymphoma and chronic lymphocytic leukemia also depends on endpoint, adjustment, and treatment setting. Prediagnostic associations in human immunodeficiency virus infection, transplantation, and population cohorts do not establish screening utility. In Waldenström macroglobulinemia, involved-chain kinetics may supplement established assessment in selected patients, although clinical benefit from sFLC-directed management has not been demonstrated. Historical treatment regimens, overlapping cohorts, inconsistent renal adjustment, assay differences, and limited external validation restrict transferability. The proposed framework integrates phenotype, renal function, assay, sampling time, and disease context. It is an interpretive proposal, not a validated prognostic score or treatment algorithm.
SN - 1198-0052
SN - 1718-7729
ER -