title: Prognostic significance of serum cystatin C in multiple myeloma.
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.
authors.affiliation: Department of Hematology, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany. holger.nueckel@uk-essen.de
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.forename: Christian
authors.initials: C
authors.lastname: Langer
authors.forename: Stefan
authors.initials: S
authors.lastname: Herget-Rosenthal
authors.forename: Marc
authors.initials: M
authors.lastname: Wichert
authors.forename: Roland
authors.initials: R
authors.lastname: Assert
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Peter
authors.initials: P
authors.lastname: Liebisch
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery; D011379:Prognosis; D033581:Stem Cell Transplantation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D055316:Cystatin C; D008558:Melphalan