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Prognostic significance of serum cystatin C in multiple myeloma

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Abstract

Multiple myeloma (MM) is frequently complicated by renal insufficiency, which is associated with an unfavorable prognosis. Serum cystatin C is a new and accurate marker of glomerular filtration rate. Global gene expression analysis has revealed serum cystatin C as one of the most highly upregulated genes in MM. Recent data have shown serum cystatin C as an independent prognostic marker in MM. To further elucidate the prognostic significance of serum cystatin C, we investigated pretreatment serum cystatin C levels in 68 newly diagnosed patients homogeneously treated with high-dose melphalan followed by autologous stem cell transplantation. Median serum cystatin C level in MM patients was significantly higher than in the 66 healthy controls (1.07 vs. 0.74 mg/L [p = 0.002]). Median serum cystatin C levels significantly increased with higher International Staging System (ISS) stages (stage I 0.72 mg/L; stage II 0.89 mg/L; stage III 1.28 mg/L; p < 0.0001). Higher serum cystatin C was positively correlated with higher serum levels of creatinine (r = 0.84; p < 0.0001), β2-microglobulin (r = 0.72; p < 0.0001), LDH (r = 0.43; p = 0.0003), white blood cell counts (r = 0.61; p < 0.0001) and calcium (r = 0.29; p = 0.016), and negatively correlated with lower serum albumin levels (r = 0.44; p < 0.0001) and hemoglobin levels (r = 0.31; p = 0.01). Using ROC analysis, patients with serum cystatin C levels ≥0.95 mg/L (n = 24) had a significantly shorter event-free survival (EFS) and overall survival (OS) than patients with serum cystatin C levels <0.95 mg/L (median EFS: 26 vs. 44 months, p < 0.0001; median OS: 54 vs. 68 months, p = 0.05). Moreover, the combination of serum cystatin C level and genomic aberrations further refined the prognostic information (EFS and OS) provided by either one of the factors. The level of serum cystatin C is not only a sensitive marker of renal function, but also reflects tumor burden and delivers prognostic information in MM.

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Acknowledgments

We are indebted to numerous colleagues for their generous contribution of information on the clinical course and treatment histories of the study patients. Holger Nückel was supported by the Adolf Messer Stiftung.

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Authors and Affiliations

  1. Department of Hematology, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany

    Holger Nückel & Ulrich Dührsen

  2. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    Christian Langer, Hartmut Döhner & Peter Liebisch

  3. Department of Internal Medicine, Rotes Kreuz Krankenhaus Bremen, Bremen, Germany

    Stefan Herget-Rosenthal

  4. Department of Clinical Chemistry, Medical Faculty, University of Duisburg-Essen, Essen, Germany

    Marc Wichert & Roland Assert

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  1. Holger Nückel
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  2. Christian Langer
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  3. Stefan Herget-Rosenthal
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Correspondence to Holger Nückel.

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Nückel, H., Langer, C., Herget-Rosenthal, S. et al. Prognostic significance of serum cystatin C in multiple myeloma. Int J Hematol 95, 545–550 (2012). https://doi.org/10.1007/s12185-012-1049-2

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  • DOI: https://doi.org/10.1007/s12185-012-1049-2

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