title: Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD can discriminate patients at high risk of steroid refractory acute GVHD.
abstract: Steroid refractory acute GVHD (SR aGVHD) is associated with high morbidity and mortality. This study attempted to generate a risk model for SR aGVHD using 259 single nucleotide polymorphisms (SNPs) in 53 genes of recipients and donors. A total of 268 patients with aGVHD who were treated with systemic steroids were included. Patients were randomly divided into training (n=180) and validation sets (n=88). Clinical risk factors were also evaluated. In the training set, 85 (47.2%) developed SR aGVHD. Gastrointestinal involvement (P<0.0001) and donor genotypes of IL6 (rs1800797; P=6.2 × 10(-4)) and IFNG (rs2069727; P=4.4 × 10(-4)) were significant risk factors. Scores were assigned to the above risk factors. Patients were divided into low (score 0, n=74) vs high risk (scores 1-3; n=106) in risk model. Higher incidence of SR aGVHD was noted in the high risk (61.3%) vs the low-risk group (27%; P<0.0001, odds ratio (OR) 4.28). Predictive effect of risk model was replicated in the validation set (P=0.0045, OR 3.74). This risk model was associated with response to therapy, overall and GVHD-specific survival and non-relapse mortality. Our study suggested that this risk model could identify patients at high risk of SR aGVHD with donor genotype of IL6 (rs1800797) and IFNG (rs2069727) along with gastrointestinal involvement of aGVHD.
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: E G
authors.initials: EG
authors.lastname: Atenafu
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Uhm
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Seftel
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kuruvilla
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: H A
authors.initials: HA
authors.lastname: Messner
authors.affiliation: Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D D H
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics / Q000401:mortality; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015996:Survival Rate; D061349:Unrelated Donors
chemical_list: C573415:IFNG protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D007371:Interferon-gamma