title: Polyclonal immunoglobulin free light chain levels predict survival in myeloid neoplasms.
abstract: OBJECTIVE
  We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest.
  
  
  METHODS
  Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded.
  
  
  RESULTS
  Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95% CI, 1.3 to 2.7), and was 6.3 (95% CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels.
  
  
  CONCLUSIONS
  Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Christy M
authors.initials: CM
authors.lastname: Finke
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Preet Paul
authors.initials: PP
authors.lastname: Singh
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Katzmann
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000401:mortality*; D009391:Nephelometry and Turbidimetry; D011087:Polycythemia Vera / Q000276:immunology; D011237:Predictive Value of Tests; D055728:Primary Myelofibrosis / Q000276:immunology* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains