title: Early CMV viremia is associated with impaired viral control following nonmyeloablative hematopoietic cell transplantation with a total lymphoid irradiation and antithymocyte globulin preparative regimen.
abstract: The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control.
authors.affiliation: Division of Infectious Diseases, Stanford University Medical Center, Stanford, California 94305-5623, USA. joannas@stanford.edu
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Schaenman
authors.forename: Sumana
authors.initials: S
authors.lastname: Shashidhar
authors.forename: Chanu
authors.initials: C
authors.lastname: Rhee
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wong
authors.forename: Shelly
authors.initials: S
authors.lastname: Navato
authors.forename: Ruby M
authors.initials: RM
authors.lastname: Wong
authors.forename: Dora Y
authors.initials: DY
authors.lastname: Ho
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.forename: Laura
authors.initials: L
authors.lastname: Johnston
authors.forename: Janice M
authors.initials: JM
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D000961:Antilymphocyte Serum / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D015182:Lymphatic Irradiation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D014180:Transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents