Monitoring of human cytomegalovirus and virus-specific T-cell response in young patients receiving allogeneic hematopoietic stem cell transplantation

• Published in: PloS one Vol. 7; no. 7; p. e41648
• Main Authors: Lilleri, Daniele, Gerna, Giuseppe, Zelini, Paola, Chiesa, Antonella, Rognoni, Vanina, Mastronuzzi, Angela, Giorgiani, Giovanna, Zecca, Marco, Locatelli, Franco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.07.2012; Public Library of Science (PLoS)
• Subjects: Adolescent; Binomial distribution; Biology; Blood; Care and treatment; CD4 antigen; CD8 antigen; Child; Child, Preschool; Cytokines; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus - physiology; Cytomegalovirus infections; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - immunology; Deoxyribonucleic acid; Development and progression; Disease susceptibility; DNA; Female; Graft-versus-host reaction; Health aspects; Health risks; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Immunity; Immunology; Infant; Infection; Infections; Lymphocytes; Lymphocytes T; Male; Medical research; Medicine; Patients; Species Specificity; Stem cell transplantation; Stem cells; T cell receptors; T cells; T-Lymphocytes - immunology; Therapy; Transplantation; Transplantation, Homologous - adverse effects; Transplants & implants; Viral infections; Viruses; Young Adult; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041648

In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, outcome of human cytomegalovirus (HCMV) infection results from balance between viral load/replication and pathogen-specific T-cell response. Using a cut-off of 30,000 HCMV DNA copies/ml blood for pre-emptive therapy and cut-offs of 1 and 3 virus-specific CD4(+) and CD8(+) T cells/µl blood for T-cell protection, we conducted in 131 young patients a prospective 3-year study aimed at verifying whether achievement of such immunological cut-offs protects from HCMV disease. In the first three months after transplantation, 55/89 (62%) HCMV-seropositive patients had infection and 36/55 (65%) were treated pre-emptively, whereas only 7/42 (17%) HCMV-seronegative patients developed infection and 3/7 (43%) were treated. After 12 months, 76 HCMV-seropositive and 9 HCMV-seronegative patients (cumulative incidence: 90% and 21%, respectively) displayed protective HCMV-specific immunity. Eighty of these 85 (95%) patients showed spontaneous control of HCMV infection without additional treatment. Five patients after reaching protective T-cell levels needed pre-emptive therapy, because they developed graft-versus-host disease (GvHD). HSCT recipients reconstituting protective levels of HCMV-specific T-cells in the absence of GvHD are no longer at risk for HCMV disease, at least within 3 years after transplantation. The decision to treat HCMV infection in young HSCT recipients may be taken by combining virological and immunological findings.