Lack of IFN-gamma 2/2 homozygous genotype independently of recipient age and intensity of conditioning regimen influences the risk of aGVHD manifestation after HLA-matched sibling haematopoietic stem cell transplantation

A total of 110 patients (71 adults and 39 children) who received allogeneic haematopoietic stem cell transplantation from HLA-matched sibling donors were studied for the incidence of acute graft-versus-host disease (aGvHD) in relation to IFN-gamma gene microsatellite polymorphism. A strong tendency was observed towards the lower incidence of grades II-IV aGvHD in patients having an IFN-gamma 2/2 genotype as compared to the recipients with other IFN-gamma genotypes (0.12 vs 0.33, P = 0.06). This relationship was independent of the intensity of conditioning regimen and diagnosis. IFN-gamma polymorphic features, together with other clinical and biological factors (patient's age, donor-recipient gender, diagnosis, conditioning regimen, transplant material and GvHD prophylaxis), were subjected to multivariate analysis for aGvHD manifestation in order to exclude indirect association of the IFN-gamma 2/2 genotype. In multivariate analysis, myeloablative therapy (OR = 11.462, P = 0.013), recipient age (OR = 4.896, P = 0.009) and lack of IFN-gamma 2/2 genotype (OR = 4.311, P = 0.048) were found to significantly contribute to the development of grade II-IV aGvHD, while type of GvHD prophylaxis showed less-strong influence (OR = 2.963, P = 0.066). Thus, it appeared that the IFN-gamma 2/2 genotype constituted an independent and protective factor associated with a decreased risk of grade II-IV aGvHD. However, this genotype was not found to be associated with the risk of cGvHD or survival.