Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD can discriminate patients at high risk of steroid refractory acute GVHD

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 x 10(-4)) and IFNG (rs2069727; P = 4.4 x 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.