title: Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+) lymphocytes are independent risk factors for cytomegalovirus reactivation with a high number of copies in hematopoietic stem cell transplantation recipients.
abstract: 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.
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experi-mental Therapy, Polish Academy of Science, Wroclaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskula
authors.forename: Dorota
authors.initials: D
authors.lastname: Dlubek
authors.forename: Dorota
authors.initials: D
authors.lastname: Duda
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.forename: Anna
authors.initials: A
authors.lastname: Mlynarczewska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000628:therapy / Q000821:virology; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000097:blood / Q000235:genetics / Q000401:mortality; D018900:Dinucleotide Repeats; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D006402:Hematologic Diseases / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014184:Transplantation, Homologous; D014775:Virus Activation
chemical_list: D007371:Interferon-gamma