Cytomegalovirus (CMV) reactivation was analyzed in 92 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) in relation to the proportion of CD4(+) lymphocytes in blood and a microsatellite polymorphism within the first intron of the interferon-gamma (IFNG) gene. CMV reactivation was found in 50% of the HSCT recipients; in 30% of these individuals, the level of CMV copies exceeded 100 per 10(5) peripheral blood (PB) cells on at least one occasion during the 100-day post-HSCT observation period. This high CMV copy level was most frequently found between 31 and 60 days post-HSCT (P = .021). Patients with > or = 100 CMV copies/10(5) cells were characterized by poorer overall survival (OS) compared with those lacking CMV copies or having < 100 CMV copies/10(5) cells (P = .04), and they suffered from severe post-HSCT complications, including acute graft-versus-host disease (aGVHD) and relapse. Thus, patients with > or = 100 CMV copies/10(5) cells were designated as having clinically significant CMV reactivation. Patients with < 10% CD4(+) lymphocytes had a higher number of CMV DNA copies than those with higher proportions of CD4(+) lymphocytes (0.62 vs 0.21, P = .001; mean +/- SEM, 4422 +/- 1667 vs 937 +/- 662 CMV copies/10(5) cells, P < .001, for the proportion of cases with reactivation and numbers of copies, respectively). Similarly, patients carrying 2 IFNG 13-CA-repeat alleles (homozygotes) had more frequent CMV reactivation (0.50 vs 0.26; P = .039) and a higher CMV load (4111 +/- 1699 vs 950+/-591 CMV copies/10(5) cells; P = .041) compared with those with other IFNG microsatellite allele constellations. Multivariate analysis demonstrated that the IFNG 13-CA-repeat homozygous genotype (odds ratio [OR] = 0.221; P = .044), a low proportion of CD4(+) lymphocytes (OR = 0.276; P = .050), and a lack of optimal (10/10 alleles) donor-recipient HLA match (OR = 15.19; P = .006) were independent risk factors for CMV reactivation with a high number of copies.

Summary Recent studies have shown that interferon‐γ gene (IFNG) polymorphism constitutes a risk factor for acute and chronic graft‐versus‐host disease (GvHD) after allogeneic haematopoietic stem cell transplantation (HSCT). Patients with IFNG 3/3 have been found to be more prone to GvHD. This rather puzzling result, as 3/3 genotype is associated with a decreased IFN‐γ production, was investigated in the present study in the context of Epstein–Barr virus (EBV) reactivation. Microsatellite polymorphism (CA)n within the first intron of IFNG gene was assessed in 83 HSCT recipients and related to EBV load. Quantification of EBV copies was performed by a real‐time polymerase chain reaction in peripheral blood cells taken from the patients 2–3 months after HSCT. It was found, that patients having IFNG 3/3 genotype presented with a high number of EBV copies (over 10/105 blood cells) when compared with the recipients with other IFNG genotypes (10/14 vs. 17/69, P < 0·001). This association was independent of recipient's age, underlying disease, conditioning regimen, type of donor, source of stem cells or pretransplant donor and recipient EBV serological status. Thus IFNG 3/3 genotype, known to be associated with a decreased IFN‐γ production, appeared as a factor significantly contributing to the risk of EBV reactivation after allogeneic HSCT.

Summary: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 ¼ 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 ¼ 11.462, P ¼ 0.013), recipient age (OR ¼ 4.896, P ¼ 0.009) and lack of IFN-gamma 2/2 genotype (OR ¼ 4.311, P ¼ 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 ¼ 2.963, P ¼ 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.