title: Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells.
abstract: A semiquantitative polymerase chain reaction assay was used to monitor the blood levels of Epstein-Barr virus (EBV)-DNA in 9 patients receiving allogeneic bone marrow transplants (BMT). Four of 5 recipients of HLA-mismatched T-cell-depleted grafts showed a 4- to 5-log increase of EBV-DNA within 1 to 3 months after BMT. Administration of 2 to 4 infusions of 10(7) EBV-specific cytotoxic T-lymphocytes (CTLs)/m(2) starting from the time of maximal virus load resulted in a 2- to 3-log decrease of virus titers in 3 patients. One patient, who received a T-cell culture lacking a major EBV-specific component, progressed to fatal EBV-positive lymphoma. Administration of EBV-CTLs before the onset of the EBV-DNA peak resulted in stabilization of the virus titers within 2 to 3 logs above the normal levels in the fifth patient. A moderate increase of virus titers was also detected in 3 of 4 patients receiving unmanipulated HLA-matched grafts, whereas 1 patient with Wiskott-Aldrich syndrome reached a 5-log increase of EBV-DNA load within 70 days after BMT. Our results suggest that a rapid increase of circulating EBV-DNA occurs in the absence of EBV-specific T-cell precursors or in the presence of congenital immune defects that prevent the reestablishment of virus-specific immunity. Prophylactic administration of EBV-CTLs early after BMT appears to provide the most effective protection against the development of EBV-associated lymphoproliferative disease.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Gustafsson
authors.forename: V
authors.initials: V
authors.lastname: Levitsky
authors.forename: J Z
authors.initials: JZ
authors.lastname: Zou
authors.forename: T
authors.initials: T
authors.lastname: Frisan
authors.forename: T
authors.initials: T
authors.lastname: Dalianis
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: O
authors.initials: O
authors.lastname: Ringden
authors.forename: J
authors.initials: J
authors.lastname: Winiarski
authors.forename: I
authors.initials: I
authors.lastname: Ernberg
authors.forename: M G
authors.initials: MG
authors.lastname: Masucci
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology / Q000628:therapy*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification*; D006648:Histocompatibility; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects; D016219:Immunotherapy, Adoptive; D007223:Infant; D008223:Lymphoma / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012306:Risk; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000150:complications / Q000453:epidemiology / Q000628:therapy*; D019562:Viral Load; D014766:Viremia / Q000628:therapy / Q000821:virology*
chemical_list: D004279:DNA, Viral; D006680:HLA Antigens