title: Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation.
abstract: The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/μl vs. 0.3/μl; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.
authors: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain; Clinical Hematology, Department of Hematology, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
authors: Ildefonso
authors: I
authors: Espigado
authors: Fátima
authors: F
authors: de la Cruz-Vicente
authors: Omar J
authors: OJ
authors: BenMarzouk-Hidalgo
authors: Irene
authors: I
authors: Gracia-Ahufinger
authors: Jose R
authors: JR
authors: Garcia-Lozano
authors: Manuela
authors: M
authors: Aguilar-Guisado
authors: Jose M
authors: JM
authors: Cisneros
authors: Alvaro
authors: A
authors: Urbano-Ispizua
authors: Pilar
authors: P
authors: Perez-Romero
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D000998:Antiviral Agents / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D011446:Prospective Studies; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000209:etiology / Q000276:immunology*; D014775:Virus Activation; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000998:Antiviral Agents
keywords: allogeneic stem cell transplantation; cytomegalovirus infection; cytomegalovirus-specific immune response