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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5418-5422.
Prepublished online as a Blood First Edition Paper on February 20, 2009; DOI 10.1182/blood-2008-12-195008.
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CLINICAL TRIALS AND OBSERVATIONS
A monoclonal gammopathy precedes multiple myeloma in most patients
Brendan M. Weiss1,
Jude Abadie2,
Pramvir Verma3,
Robin S. Howard4, and
W. Michael Kuehl5
1 Hematology-Oncology Service, Department of Medicine and
2 Department of Pathology and Area Laboratory Services, Walter Reed Army Medical Center, Washington, DC;
3 Hematology-Oncology Service, Department of Medicine, Womack Army Medical Center, Fort Bragg, NC;
4 Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC; and
5 Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD
Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.
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