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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 807-814
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
Åsa Gustafsson,
Victor Levitsky,
Jie-Zhi Zou,
Teresa Frisan,
Tina Dalianis,
Per Ljungman,
Olle Ringden,
Jacek Winiarski,
Ingemar Ernberg, and
Maria G. Masucci
From the Microbiology and Tumor Biology Center, Karolinska Institet;
Department of Pediatrics, Department of Immunology, Microbiology,
Pathology, and Infectious Diseases, Department of Hematology, and
Center for Allogeneic Stem Cell Transplantation, Huddinge Hospital,
Stockholm, Sweden.
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 107 EBV-specific
cytotoxic T-lymphocytes (CTLs)/m2 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.
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