Serum Free Light Chain in Lymphoproliferative Disorders
Serum Free Light Chain in Lymphoproliferative Disorders
Non-Hodgkin lymphoma comprises a large number of subtypes that show distinct biologic, molecular, and cytogenetic characteristics. Moreover, some patients experience clinical remission, some experience disease stabilization for a long period, and others experience rapid medical deterioration. Because of their highly variable clinical courses, identification of molecular and biological prognostic markers becomes mandatory to provide new insights into risk stratification of these patients.
Several studies have shown that M protein can be produced in other hematologic malignancies, mainly NHL. Using conventional techniques (PEL/IFE), Alexanian documented the presence of M protein in 7% of 640 patients with diffuse large B-cell lymphoma (DLBCL) and CLL. In a cohort study from the Mayo Clinic which included 430 patients with IgM monoclonal protein, 7% of patients had NHL and 5% had CLL. Lin et al studied 382 patients with lymphoid neoplasm with IgM M protein. Fifty-nine percent of these patients had Waldenström macroglobulinemia, 20% had CLL, 7% had marginal zone lymphoma (MZL), 5% had follicular lymphoma (FL), 3% had mantle cell lymphoma (MCL), 2% had DLBCL, and 4% were miscellaneous. Asatiani et al described 7 (27%) of 26 patients with extranodal MZL having an M-protein spike.
Table 1 summarizes the frequency of increased sFLCr from various studies in the literature. The initial evaluation of the frequency of monoclonal sFLC in patients with other B-cell malignancies was published by Martin et al in 2007. Frozen serum samples from 226 patients (NHL: n = 208, CLL: n = 18) collected at the Mayo Clinic/Lymphoma SPORE serum bank were tested for M protein with the sFLC assay, SPEP, and IFE. Overall, M protein was detected in 24% (54/226) of samples (NHL: n = 46, CLL: n = 8). Of these 54 patients, 34 (63%) were sFLC-positive (NHL: n = 27, CLL: n = 7), whereas 35 patients were identified by means of SPEP/IFE (NHL: n = 33, CLL: n = 2). In addition, M protein was detected in 19 patients (NHL: n = 13, CLL: n = 6) with sFLC only, and 20 patients (NHL: n = 19, CLL: n = 1) with SPEP/IFE only. Within NHL, the highest incidence of sFLC was in patients with MCL (9/25, 36%), followed by small lymphocytic leukemia (SLL) (6/25, 24%), lymphoma of mucosa-associated lymphoid tissue (3/19, 16%), lymphoplasmacytoid lymphoma (2/14, 14%), Burkitt lymphoma (2/17, 12%), DLBCL (2/25, 8%), and FL (3/75, 4%). In conclusion, the sFLC assay improved the detection of M proteins when combined with standard SPEP/IFE in a substantial fraction of patients with NHL/CLL. However, the relationship of M protein and sFLC to pathogenesis, disease course, response to therapy, prognosis, or survival in these patients with NHL or CLL was not investigated.
Lymphoproliferative Disorders and sFLC
Non-Hodgkin lymphoma comprises a large number of subtypes that show distinct biologic, molecular, and cytogenetic characteristics. Moreover, some patients experience clinical remission, some experience disease stabilization for a long period, and others experience rapid medical deterioration. Because of their highly variable clinical courses, identification of molecular and biological prognostic markers becomes mandatory to provide new insights into risk stratification of these patients.
Several studies have shown that M protein can be produced in other hematologic malignancies, mainly NHL. Using conventional techniques (PEL/IFE), Alexanian documented the presence of M protein in 7% of 640 patients with diffuse large B-cell lymphoma (DLBCL) and CLL. In a cohort study from the Mayo Clinic which included 430 patients with IgM monoclonal protein, 7% of patients had NHL and 5% had CLL. Lin et al studied 382 patients with lymphoid neoplasm with IgM M protein. Fifty-nine percent of these patients had Waldenström macroglobulinemia, 20% had CLL, 7% had marginal zone lymphoma (MZL), 5% had follicular lymphoma (FL), 3% had mantle cell lymphoma (MCL), 2% had DLBCL, and 4% were miscellaneous. Asatiani et al described 7 (27%) of 26 patients with extranodal MZL having an M-protein spike.
Table 1 summarizes the frequency of increased sFLCr from various studies in the literature. The initial evaluation of the frequency of monoclonal sFLC in patients with other B-cell malignancies was published by Martin et al in 2007. Frozen serum samples from 226 patients (NHL: n = 208, CLL: n = 18) collected at the Mayo Clinic/Lymphoma SPORE serum bank were tested for M protein with the sFLC assay, SPEP, and IFE. Overall, M protein was detected in 24% (54/226) of samples (NHL: n = 46, CLL: n = 8). Of these 54 patients, 34 (63%) were sFLC-positive (NHL: n = 27, CLL: n = 7), whereas 35 patients were identified by means of SPEP/IFE (NHL: n = 33, CLL: n = 2). In addition, M protein was detected in 19 patients (NHL: n = 13, CLL: n = 6) with sFLC only, and 20 patients (NHL: n = 19, CLL: n = 1) with SPEP/IFE only. Within NHL, the highest incidence of sFLC was in patients with MCL (9/25, 36%), followed by small lymphocytic leukemia (SLL) (6/25, 24%), lymphoma of mucosa-associated lymphoid tissue (3/19, 16%), lymphoplasmacytoid lymphoma (2/14, 14%), Burkitt lymphoma (2/17, 12%), DLBCL (2/25, 8%), and FL (3/75, 4%). In conclusion, the sFLC assay improved the detection of M proteins when combined with standard SPEP/IFE in a substantial fraction of patients with NHL/CLL. However, the relationship of M protein and sFLC to pathogenesis, disease course, response to therapy, prognosis, or survival in these patients with NHL or CLL was not investigated.