HEMAPHERESIS Light-chain removal by plasmapheresis in myeloma-associated renal failure Christine Cserti, Richard Haspel, Christopher Stowell, and Walter Dzik BACKGROUND: Although plasmapheresis has been recommended to reverse nephrotoxic elevations of serum free light chains (sFLCs), there are scant pub- lished data on removal of sFLC measured with modern assays. STUDY DESIGN AND METHODS: sFLC levels were recorded in two patients with myeloma-associated renal failure receiving multiple plasmapheresis procedures. RESULTS: In one patient, presenting with acute renal failure 8 months after diagnosis of k-LC myeloma, 16 plasmapheresis procedures neither reduced sFLC levels (percent removal ranging from -70% to +40%) nor improved renal function. In another patient who pre- sented with leukemic immunoglobulin A-l myeloma and acute renal failure, sFLC decreased by 30 to 60 percent after each plasmapheresis procedure, but rebounded within 5 to 10 hours. Renal failure occurred despite plasmapheresis, and hemodialysis was required. CONCLUSIONS: In both patients, plasmapheresis failed to effectively lower sFLC levels. The results provide initial biologic data supporting the conclusions of a recent randomized multicenter clinical trial in which plasmapheresis was an ineffective adjunct to chemo- therapy for myeloma-associated acute renal failure. P lasmapheresis has been recommended in light- chain myeloma complicated by renal failure 1 based on nonrandomized reports 2-4 and two small, randomized trials. 5,6 Recently, a large, ran- domized, controlled trial of plasmapheresis in myeloma- related acute renal failure showed no difference in the composite outcome of death, dialysis dependence, or glomerular filtration rate of less than 0.29 mL per s 2 per m 2 (<30 mL/min per 1.73 m 2 ). 7 Wide 95 percent confidence intervals (CIs; -8.3%-29.1%) for the 11.3 percent differ- ence in composite outcome between the groups (57.9% with plasmapheresis vs. 69.2% without; p = 0.36) might have obscured detection of benefit or risk. Furthermore, serum free light chain (sFLC) levels were not quantified. Because the rationale for plasmapheresis is removal of sFLC, it is important to correlate clinical endpoints with the efficacy of sFLC removal. Literature directly addressing sFLC removal by plas- mapheresis is scarce, because measurements had been limited by semiquantitative low sensitivity techniques. In 1983, McLeod and coworkers 8 used crossed immunoelec- tropheresis to measure sFLC levels during plasmapheresis in three patients. Immediately after plasmapheresis, levels decreased by 40 to 60 percent, but increased again quickly. Sustained reductions were achieved only in the two patients who also received chemotherapy. Accurate nephelometric measurement of sFLC has been available since 2001. 9 To our knowledge, there are no reports using this method to verify that plasmapheresis effectively removes sFLC. We report quantitative sFLC levels in two patients with myeloma and renal insufficiency treated with plasmapheresis. MATERIALS AND METHODS sFLC levels were determined using a lambda free kit (FREELITE, The Binding Site Ltd., Birmingham, UK), a monospecific antibody coated onto polystyrene latex, and a nephelometer (BN II, Dade Behring, Deerfield, IL), which quantifies light chain turbidimetrically. Plasmapheresis was performed using a continuous-flow cell separator (COBE Spectra, Gambro BCT, Lakewood, CO). Each treat- ment processed approximately one blood volume, with saline and 5 percent albumin solution as replacement. ABBREVIATION: sFLC(s) = serum free light chain(s). From the Massachusetts General Hospital, Boston, Massachusetts. Address reprint requests to: Christine Cserti, MD, University Health Network, Toronto General Hospital, 3E-306, 200 Eliza- beth Street, Toronto, Ontario M5G-2C4; e-mail: christine. cserti@uhn.on.ca. Received for publication July 13, 2006; revision received August 13, 2006, and accepted August 22, 2006. doi: 10.1111/j.1537-2995.2006.01143.x TRANSFUSION 2007;47:511-514. Volume 47, March 2007 TRANSFUSION 511