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.
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.
Jaskula
Emilia
E
Ludwik Hirszfeld Institute of Immunology and Experi-mental Therapy, Polish Academy of Science, Wroclaw, Poland.
Dlubek
Dorota
D
Duda
Dorota
D
Bogunia-Kubik
Katarzyna
K
Mlynarczewska
Anna
A
Lange
Andrzej
A
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
D007371:Interferon-gamma