new england journal
n engl j med
Robert A. Kyle, M.D., and S. Vincent Rajkumar, M.D.
From the Division of Hematology and Inter-nal Medicine, Mayo Clinic, Rochester, Min-nesota. Address reprint requests to Dr. Kyleat the Division of Hematology and InternalMedicine, Mayo Clinic, 200 First St. S.W.,Rochester, MN 55905, or at email@example.com.N Engl J Med 2004;351:1860-73.
Copyright © 2004 Massachusetts Medical Society.
ultiple myeloma is a plasma-cell neoplasm that is charac-
terized by skeletal destruction, renal failure, anemia, and hypercalcemia.
Although myeloma remains incurable, recent advances in its treatment, in-cluding the use of thalidomide and new drugs such as bortezomib and CC-5013, arepromising.
The most common symptoms on presentation are fatigue, bone pain, and recurrent in-fections.
New diagnostic criteria require the presence of at least 10 percent plasmacells on examination of the bone marrow (or biopsy of a tissue with monoclonal plas-ma cells), monoclonal protein in the serum or urine, and evidence of end-organ dam-age.
The end-organ damage that meets the criterion for the diagnosis consists of hy-percalcemia, renal insufficiency, anemia, or bone lesions (a group of findings referredto as CRAB).
Occasional patients presenting without a detectable monoclonal proteinbut otherwise meeting these diagnostic criteria are considered to have nonsecretory myeloma. The serum free light-chain assay is useful for monitoring many patients witholigosecretory and nonsecretory myeloma. The differential diagnosis includes mono-clonal gammopathy of undetermined significance (MGUS), smoldering (asymptom-atic) multiple myeloma, primary amyloidosis, solitary plasmacytoma, low-grade lym-phoma, chronic lymphocytic leukemia, and metastatic carcinoma.
The median length of survival after diagnosis is approximately three years. Recent advances have identified new prognostic markers, such as the complete deletion of chromosome 13 or its long arm, as detected by karyotyping; the t(4;14) or t(14;16)translocation; and increased density of bone marrow microvessels. These complement established markers of adverse outcomes, such as an increase in the plasma-cell–label-ing index, increased levels of serum beta
-microglobulin, low levels of serum albumin,plasmablastic features in the bone marrow, and circulating plasma cells.
evolution of mgus
The first pathogenetic step in the development of myeloma is the emergence of a lim-ited number of clonal plasma cells, clinically known as MGUS.
Patients with MGUSdo not have symptoms or evidence of end-organ damage, but they do have an annualrisk of 1 percent of progression to myeloma or a related malignant disease.
Approx-imately 50 percent of patients have translocations that involve the immunoglobulinheavy-chain locus on chromosome 14q32 and one of five partner chromosomes,11q13 (
) (the most common), 4p16.3 (
and MMSET), 6p21 (
Copyright © 2004 Massachusetts Medical Society. All rights reserved.Downloaded from www.nejm.org on March 14, 2005 . This article is being provided free of charge for use in Colombia.