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[Cancer Research 62, 715-720, February 1, 2002]
© 2002 American Association for Cancer Research

Clinical Investigations

Biological and Prognostic Significance of Interphase Fluorescence in Situ Hybridization Detection of Chromosome 13 Abnormalities ({Delta}13) in Multiple Myeloma

An Eastern Cooperative Oncology Group Study1

Rafael Fonseca2, David Harrington, Martin M. Oken, Gordon W. Dewald, Richard J. Bailey, Scott A. Van Wier, Kimberly J. Henderson, Emily A. Blood, S. Vincent Rajkumar, Neil E. Kay, Brian Van Ness and Philip R. Greipp

Mayo Clinic Department of Hematology and Internal Medicine, Department of Laboratory Medicine and Pathology, Rochester, Minnesota 55905 [R. F., G. W. D., R. J. B., S. A. V. W., K. J. H., S. V. R., N. E. K., P. R. G.]; Eastern Cooperative Oncology Group Statistical Center, Dana Farber Cancer Institute, Boston Massachusetts 02115 [D. H., E. A. B.]; Virginia Piper Cancer Institute, Minneapolis, Minnesota 55407 [M. M. O.]; and University of Minnesota, Minneapolis, Minnesota 55455 [B. V. N.]

Chromosome 13 abnormalities ({Delta}13) have been associated with an unfavorable prognosis in patients with multiple myeloma (MM). The significance of this has been unresolved because of diverse methods of detection and heterogeneous groups of patients. We conducted a study of {Delta}13 in patients entered into the Eastern Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM (median follow-up of survivors >100 months) were studied for {Delta}13, using bone marrow samples obtained at study enrollment. We used interphase fluorescence in situ hybridization with the probes LSI13 (Rb)/D13S319 with simultaneous immunofluorescence detection of bone marrow plasma cells (PCs). We detected {Delta}13 in 176 of 325 (54%) evaluable patients. Patients with {Delta}13 were more likely to have a serum monoclonal protein at a concentration <=1 g/dl (22 versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), {lambda} light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and be female (60 versus 50%; P = 0.087). The PC labeling index and {Delta}13 correlated (P = 0.03). Patients with {Delta}13 were less likely to respond to treatment (74 versus 63%; P = 0.041) and had a significantly shorter median overall survival (34.9 versus 51 months; P = 0.021). The association of {Delta}13 and survival remained an independent prognostic variable in a regression model. Among patients with {Delta}13, those receiving IFN had a worse overall survival that those not receiving the medication (P = 0.03). The presence of {Delta}13 is an important and independent adverse prognostic factor in newly diagnosed MM and is associated with specific biological features.




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