Analysis of the Reliability of Serial Paraprotein Determinations in Patients with Plasma Cell Dyscrasias

Serum protein electrophoresis on cellulose acetate membranes commonly is used to follow paraprotein levels, which helps determine therapy in patients with multiple myeloma. To recognize true changes in paraprotein levels, it is necessary to be able to distinguish true changes from random fluctuations due to intrasample variation. We, therefore, determined the interassay variability of concentration determinations for 14 paraproteins ranging from 0.5 to 5.2 g/dL and calculated standard deviations as a function of concentration. The minimum detectable difference for successive measurements was determined to be 2.8 times the appropriate standard deviation. Using these data, we constructed a nomogram from which the minimum detectable difference at a given paraprotein concentration could be read. To interpret temporal changes in paraprotein for an individual patient, a plot was constructed of the measured paraprotein concentration, plus or minus the minimum detectable difference obtained from the nomogram, against time. To evaluate the clinical usefulness of this procedure, we selected 11 patients with multiple myeloma whose serial paraprotein levels had been measured a total of 241 times (median of 20 times/patient) over one to four years. The changes in paraprotein levels were plotted and then correlated with the patient’s clinical status at each time point. The graphic representation of serial paraprotein values provided a clear picture of the course of a given patient’s disease and gave information that often was not apparent from clinical examination. This format should enable significant changes in paraprotein concentration to be detected at the earliest possible time.