TY - JOUR
T1 - Associations and prognostic interactions between circulating levels of hepcidin, ferritin and inflammatory cytokines in primary myelofibrosis
AU - Pardanani, Animesh
AU - Finke, Christy
AU - Abdelrahman, Ramy A.
AU - Lasho, Terra L.
AU - Tefferi, Ayalew
PY - 2013/4
Y1 - 2013/4
N2 - 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 × 109/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.
AB - 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 × 109/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.
UR - http://www.scopus.com/inward/record.url?scp=84875578130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875578130&partnerID=8YFLogxK
U2 - 10.1002/ajh.23406
DO - 10.1002/ajh.23406
M3 - Article
C2 - 23450619
AN - SCOPUS:84875578130
SN - 0361-8609
VL - 88
SP - 312
EP - 316
JO - American journal of hematology
JF - American journal of hematology
IS - 4
ER -