Molecular Monitoring of Minimal Residual Disease in the Peripheral Blood of Patients with Multiple Myeloma Mark Korthals, Nina Sehnke, Ralf Kronenwett,

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Molecular Monitoring of Minimal Residual Disease in the Peripheral Blood of Patients with Multiple Myeloma Mark Korthals, Nina Sehnke, Ralf Kronenwett, Thomas Schroeder, Tobias Strapatsas, Guido Kobbe, Rainer Haas, Roland Fenk Biology of Blood and Marrow Transplantation Volume 19, Issue 7, Pages 1109-1115 (July 2013) DOI: 10.1016/j.bbmt.2013.04.025 Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 MRD in PB at a single time point. MRD levels in PB were analyzed in samples obtained either at the time of first diagnosis (n = 12), approximately 1 week before (n = 21) or 3 months after (n = 32) HDT and PBSCT, or at the time of relapse (n = 22). Biology of Blood and Marrow Transplantation 2013 19, 1109-1115DOI: (10.1016/j.bbmt.2013.04.025) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Comparison of MRD levels of 67 paired samples from PB and BM of 36 patients. PB and BM samples were taken on the same day and represent different time points during the course of disease. PCR results of paired samples are indicated by lines. Biology of Blood and Marrow Transplantation 2013 19, 1109-1115DOI: (10.1016/j.bbmt.2013.04.025) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Correlation of the MRD levels in PB at single time points with the clinical outcome of patients. The EFS of patients with negative or positive PCR results in PB either at the time of first diagnosis (A), 1 week before (C), or 3 months after (E) HDT and autologous PBSCT was analyzed by Kaplan-Meier plots and the log rank test. Similarly, the OS of the patients with negative or positive PCR results at the time of first diagnosis (B), before (D), or after (F) HDT and autologous PBSCT was analyzed. FD indicates first diagnosis; pre-MRD, MRD level before HDT and autologous PBSCT; post-MRD, MRD level after HDT and autologous PBSCT. Biology of Blood and Marrow Transplantation 2013 19, 1109-1115DOI: (10.1016/j.bbmt.2013.04.025) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Sequential monitoring of MRD in PB. MRD levels in consecutive PB samples are shown for 29 patients with relapse after HDT and autologous PBSCT as a function of time after HDT. One log steps of the 2IgH/β-actin ratio are depicted by circles with different color fills. In 19 patients (66%) an increase of the 2IgH/β-actin ratio of more than 1 log step (arrows) could be detected in PB before clinical disease progression was observed. Biology of Blood and Marrow Transplantation 2013 19, 1109-1115DOI: (10.1016/j.bbmt.2013.04.025) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Comparison of the survival of patients with a molecular relapse before clinical relapse. The OS was calculated as time from clinical relapse and analyzed by Kaplan-Meier plots and the log rank test. Biology of Blood and Marrow Transplantation 2013 19, 1109-1115DOI: (10.1016/j.bbmt.2013.04.025) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions