title: IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes.
abstract: Recent studies suggest a powerful prognostic value for plasma cytokine levels in primary myelofibrosis (interleukin (IL)-2R, IL-8, IL-12, IL-15 and C-X-C motif chemokine 10 (CXCL10)) and large-cell lymphoma (IL-2R, IL-8, IL-10, IL-12, CXCL9 and CXCL10). To examine the possibility of a similar phenomenon in myelodysplastic syndromes (MDS), we used multiplex enzyme-linked immunosorbent assay to measure 30 plasma cytokines in 78 patients with primary MDS. Compared with normal controls (n = 35), the levels of 19 cytokines were significantly altered. Multivariable analysis identified increased levels of CXCL10 (P<0.01), IL-7 (P = 0.02) and IL-6 (P = 0.07) as predictors of shortened survival; the survival association remained significant when the Cox model was adjusted for the International Prognostic Scoring System, age, transfusion-need or thrombocytopenia. MDS patients with normal plasma levels of CXCL10, IL-7 and IL-6 lived significantly longer (median survival 76 months) than those with elevated levels of at least one of the three cytokines (median survival 25 months) (P<0.01). Increased levels of IL-6 were associated with inferior leukemia-free survival, independent of other prognostic factors (P = 0.01). Comparison of plasma cytokines between MDS (n = 78) and primary myelofibrosis (n = 127) revealed a significantly different pattern of abnormalities. These observations reinforce the concept of distinct and prognostically relevant plasma cytokine signatures in hematological malignancies.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. pardanani.animesh@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: C
authors.initials: C
authors.lastname: Finke
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: A
authors.initials: A
authors.lastname: Al-Kali
authors.forename: K H
authors.initials: KH
authors.lastname: Begna
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054357:Chemokine CXCL10 / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D015851:Interleukin-7 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C508600:IL6 protein, human; C508605:IL7 protein, human; D015850:Interleukin-6; D015851:Interleukin-7