title: IL15 levels on day 7 after hematopoietic cell transplantation predict chronic GVHD.
abstract: Chronic GVHD (cGVHD) is an important complication of allogeneic hematopoietic cell transplantation (HCT). As preemptive therapy might be efficacious if administered early post transplant, we set out to determine whether cGVHD can be predicted from the serum level of a biomarker on day 7 or 28. In a discovery cohort of 153 HCT recipients conditioned with BU, fludarabine and rabbit antithymocyte globulin (ATG), we determined serum levels of B-cell-activating factor, vascular endothelial growth factor, soluble TNF-α receptor 1, soluble IL2 receptor α, IL5, IL6, IL7, IL15, γ-glutamyl transpeptidase, cholinesterase, total protein, urea and ATG. Patients with low levels of IL15 (<30.6 ng/L) on day 7 had 2.7-fold higher likelihood of developing significant cGVHD (needing systemic immunosuppressive therapy) than patients with higher IL15 levels (P<0.001). This was validated in a validation cohort of 105 similarly-treated patients; those with low IL15 levels had 3.7-fold higher likelihood of developing significant cGVHD (P=0.001). Low IL15 was not associated with relapse; it trended to be associated with acute GVHD and was associated with low infection rates. In conclusion, low IL15 levels on day 7 are predictive of cGVHD, and thus could be useful in guiding preemptive therapy.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Pratt
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Ugarte-Torres
authors.forename: M
authors.initials: M
authors.lastname: Hoegh-Petersen
authors.forename: P J
authors.initials: PJ
authors.lastname: Podgorny
authors.forename: A W
authors.initials: AW
authors.lastname: Lyon
authors.forename: T S
authors.initials: TS
authors.lastname: Williamson
authors.forename: F M
authors.initials: FM
authors.lastname: Khan
authors.forename: M A
authors.initials: MA
authors.lastname: Chaudhry
authors.forename: A
authors.initials: A
authors.lastname: Daly
authors.forename: D A
authors.initials: DA
authors.lastname: Stewart
authors.forename: J A
authors.initials: JA
authors.lastname: Russell
authors.forename: A
authors.initials: A
authors.lastname: Grigg
authors.forename: D
authors.initials: D
authors.lastname: Ritchie
authors.forename: J
authors.initials: J
authors.lastname: Storek
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D019409:Interleukin-15 / Q000097:blood* / Q000276:immunology; D007938:Leukemia / Q000097:blood* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D019409:Interleukin-15