Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma in a Solid Organ Transplant

Jimenez-Zepeda et al. (1) reported in the recent issue of Transplantation that in the 34 patients identified preoperatively with monoclonal gammopathy of undetermined significance (MGUS) none went on to develop multiple myeloma. The authors concluded that routine testing for MGUS before transplantation is not prognostic nor a contraindication to transplant, and therefore it is not recommended. We argue for a more conservative approach, for there are patients with MGUS who are at high risk for progression to multiple myeloma, which is generally considered a contraindication to transplantation. It is now widely accepted that multiple myeloma is preceded by precursor MGUS disease (2). The rate of progression from MGUS to multiple myeloma is predicted to be roughly 1% per year (3). Recent data have allowed the clinician to risk stratify the patient with MGUS and prognosticate their risk of progression to multiple myeloma based on the amount of monoclonal protein, immunoglobulin type, and free light chain (FLC) ratio (4). Forty percent of patients with MGUS are considered low risk for progression to multiple myeloma with an absolute risk of progression at 20 years of 5%, as defined by serum protein electrophoresis less than 1.5, IgG subtype, and a normal FLC ratio (5). Absolute risk of progression can be as high as 58% in high-risk individuals, those who do not meet the above listed criteria (5). Even with this recent study by Jimenez-Zepeda et al. (1) in Transplantation, we contend that the outcome of preexisting (MGUS) after a solid organ transplant is largely unknown. It could be that the 34 patients who were identified were mostly low-risk patients and not high risk for progressing to multiple myeloma. In our practice, we report the occurrence of multiple myeloma in a patient 2 years after a deceased donor kidney transplant, who was found to have a diagnosis of MGUS preoperatively. M.K. is a 55-year-old woman who developed membranoproliferative glomerulonephritis in the 1990s, which progressed to end-stage renal disease, requiring hemodialysis in 2005. In 2007, she was transplanted with a 23-year-old deceased donor six-antigen match kidney. She did well postoperatively but developed a persistent anemia that was resistant to erythropoietin. Workup by hematology revealed an M spike of 3.6 g/dL. Bone marrow biopsy at the time revealed 70% plasma cells. We wondered if she had the presence of an M spike on her pretransplant serum. A serum protein electrophoresis on her 2005 serum revealed an M spike of 2.6 gm/dL and a FLC ratio of 22, clearly demonstrating the presence of MGUS preoperatively (Fig. 1).FIGURE 1.: A serum protein electrophoresis (SPEP) of a patient who had pretransplant monoclonal gammopathy of undetermined significance then went on to develop posttransplant multiple myeloma. This figure demonstrates her preoperative SPEP demonstrating an M spike (right most pink spike). The blue line represents the normal SPEP pattern. The gel appears in the top left corner. The patient subsequently went on to develop multiple myeloma 2 years after receiving a kidney transplant.Whether immunosuppressive regimens required by organ transplantation affect the progression of MGUS to multiple myeloma is still unknown and deserves more study. In a large retrospective study where the United Network for Organ Sharing data were matched with Medicare claims for posttransplantation lymphoproliferative disease, there does seem to be an increased risk of multiple myeloma after kidney transplant and an increase risk with T-cell-directed induction therapy (6). In all, it is likely that many MGUS patients are at low risk of progressing to multiple myeloma, as supported by a recent study by Jimenez-Zepeda et al.; however, as practitioners we need to determine which patients are at high risk of progressing to multiple myeloma after solid organ transplant—and those patients should generally be excluded from transplantation. Robert R. Redfield Ali Naji Department of Surgery Hospital of the University of Pennsylvania Philadelphia, PA