Oligoclonal Pattern/Abnormal Protein Bands in Post-Treatment Plasma Cell Myeloma Patients: Implications for Protein Electrophoresis and Serum Free Light Chain Assay Results

Abstract

BackgroundThe impact of autologous stem cell transplantation (ASCT) in plasma cell myeloma patients on the frequency, quality, and timing of oligoclonal pattern in serum protein electrophoresis/immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA) was evaluated.MethodsLaboratory results and clinical data for 251 patients with plasma cell myeloma, who had SPEP/SIFE and/or SFLCA performed between January 2010 and December 2016 were reviewed. The results for SPEP/SIFE and SFLCA were compared in patients with ASCT to those without ASCT. The implications of oligoclonal pattern in interpretation of SPEP/SIFE and SFLCA - κ/λ ratio were addressed.ResultsIn 251 patients, a total of 3,134 observations, of either SPEP/SIFE and/or SFLCA, were reviewed. One hundred fifty-nine patients received ASCT. The incidence of oligoclonal patterns was significantly higher after ASCT. More than half of the oligoclonal patterns developed in the first year after transplantation. In 13 of the 84 patients with lambda chain restricted plasma cell myeloma, the κ/λ ratio was kappa dominant in the presence of oligoclonal pattern. There was no reversal of κ/λ ratio in patients with kappa chain restricted plasma cell myelomas.ConclusionsASCT is associated with significantly higher incidence of oligoclonal patterns than with chemotherapy alone. The presence of oligoclonal patterns has the potential to interfere with the interpretation of SPEP/SIFE and ascertainment of complete remission. At a minimum, the oligoclonal pattern caused an incorrect kappa dominant κ/λ ratio in 15.5% of patients with lambda chain restricted plasma cell myeloma. If a similar rate were to be applied to the 167 kappa chain myeloma patients, about 26 of these would have displayed an erroneous kappa chain dominant κ/λ ratio. The presence of oligoclonal pattern further degrades the performance of already dubious SFLCA. The need for recording the location of monoclonal spike in SPEP/SIFE and higher resolution protein electrophoresis methods are highlighted.

Comparison of Serum Immunoglobulin Free Light Chains Assay and Serum Immunofixation Electrophoresis in Patient Transplanted for Multiple Myeloma

“…Nevertheless recently, some other authors [14][15][16][17] have raised doubts about the real usefulness of sFLC, especially since the number of false positives and false negatives compared to serum protein electrophoresis (SPE) and sIFE are quite substantial. In the other hand, many factors can enhance those discrepancies such as renal failure [18], propensity of sFLC (especially those λ) to aggregate or polymerase, which may contributes to underestimation of λ FLC [15], hyper or hypogammaglobulinemia [19].…”

“…But the point still remaining is that sFLC measurement has the same utility and impact on MM diagnosis and monitoring. While some authors [16,17] reject the utility of sFLC in the monitoring of MM, because there is neither any benefit from sFLC ratio normalization in clinical remission in myeloma patients in terms of progression-free survival or overall survival [16], nor any significance of the presence of sFLC, especially in autologous stem cell transplantation (ASCT) where the apparition of oligoclonal pattern (which aren't synonymous to malignant monoclonal proteins), further degrades the performance of sFLC assay [17]. Recently some authors Michallet M & Greil C [20,21] reported that the use of serum Heavy/light chain is valuable as diagnosis and monitoring tool in MM patients, and that it correlates with clinical outcome in those patients.…”

Prospective Identification of Oligoclonal/Abnormal Band of the Same Immunoglobulin Type as the Malignant Clone by Differential Location of M-Spike and Oligoclonal Band

“…SPEP was performed by agarose gel electrophoresis using Helena SPIFE 3000 system. Quantitative evaluation for the usual proteins and any M-proteins was performed by scanning the gel at 595 nm on an EDC densitometer [ 3 , 7 , 13 ]. If the monoclonal protein overlapped a normal protein band, the concentration of the combined peak was reported.…”

“…IgG kappa oligoclonal bands are the usual prominent “abnormal” bands and IgG kappa is also the most common immunoglobulin type of myelomas. Thus, for proper identification of stringent complete response and to avoid unnecessary treatment, it is imperative that we distinguish an oligoclonal band as not a residual or recurrent tumor, even though it is of the same immunoglobulin type as the initial malignant clone [ 13 ].…”

“…As reported in the results of a retrospective study, recording the location of the original monoclonal peak facilitates the identification of oligoclonal bands that may appear in a different area of the SPEP/SIFE results [ 13 ]. We also reported the use of recording the location of the peak as a tool in ensuring specimen integrity, a form of delta check for specimen mislabeling [ 14 ].…”