title: Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis.
abstract: Iron homeostasis is dysregulated in primary myelofibrosis (PMF), given the high prevalence of anemia, need for red blood cell (RBC) transfusions, and disease-associated inflammatory state. We measured plasma hepcidin levels in 203 consecutive PMF patients at the time of first referral; hepcidin levels were significantly higher as compared to healthy controls (P < 0.0001), and were correlated with hemoglobin of <10 g/dL, RBC transfusion requirement, serum ferritin of >500 µg/L, higher dynamic international prognostic scoring system (DIPSS)-plus risk category, the presence of circulating blasts, age of >65 years, and leukocyte count of <4 × 10(9) /L. Increased hepcidin levels predicted for inferior survival independent of six out of the eight DIPSS-plus prognostic parameters (hazard ratio [HR] = 1.8; P = 0.02), but not when RBC transfusion requirement, hemoglobin of <10 g/dL, or increased serum ferritin were included in the Cox model. Multivariable analysis that considered the four overlapping prognostic variables revealed that increased hepcidin (HR = 1.9; P = 0.03) and increased ferritin (HR = 2.3; P = 0.04), but not hemoglobin of <10 g/dL or RBC transfusion requirement, independently retained their significance for predicting survival. Accordingly, increased levels of both hepcidin and serum ferritin (seen in 29% of patients) predicted inferior survival independent of DIPSS-plus or increased inflammatory cytokine levels (HR = 2.4; P = 0.002), and could be considered in future prognostic models for PMF.
authors: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. Pardanani.animesh@mayo.edu
authors: Animesh
authors: A
authors: Pardanani
authors: Christy
authors: C
authors: Finke
authors: Ramy A
authors: RA
authors: Abdelrahman
authors: Terra L
authors: TL
authors: Lasho
authors: Ayalew
authors: A
authors: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D017707:Erythrocyte Transfusion; D005260:Female; D005293:Ferritins / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007501:Iron / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000097:blood* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D016207:Cytokines; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D005293:Ferritins; D007501:Iron