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Blood, 15 January 2008, Vol. 111, No. 2, pp. 785-789.
Prepublished online as a Blood First Edition Paper on October 17, 2007; DOI 10.1182/blood-2007-08-108357.
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Submitted August 21, 2007
Accepted September 17, 2007
Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma
Angela Dispenzieri*, Robert A. Kyle, Jerry A. Katzmann, Terry M. Therneau, Dirk Larson, Joanne Benson, Raynell J. Clark, L. Joseph Melton III, Morie A. Gertz, Shaji K. Kumar, Rafael Fonseca, Diane F. Jelinek, and S. Vincent Rajkumar
Department of Internal Medicine, Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN, United States
Department of Internal Medicine, Division of Hematology and Oncology, Mayo Clinic College of Medicine, Scottsdale, AZ, United States
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, United States
* Corresponding author; email: dispenzieri.angela{at}mayo.edu.
We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active myeloma. Baseline serum samples obtained within 30 days of diagnosis were available in 273 patients with SMM seen from 1970 to 1995. At a median follow-up of surviving patients of 12.4 years, transformation to active disease has occurred in 59%. The best break-point for predicting risk of progression was a FLC ratio < 0.125 > 8 (hazard ratio, 2.3; 95% CI, 1.6-3.2). The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of plasma cells in the bone marrow (BMPC) and size of serum M-proteins (BMPC 10% and serum M protein 3 g/dL; BMPC 10% but serum M protein < 3 g/dL; and serum M protein 3 g/dL but BMPC < 10%). Incorporating the FLC ratio into the risk model, the 5 year progression rates in high-, intermediate-, and low-risk groups were 76, 51, and 25%, respectively. The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM.

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