Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative disease.
The evaluation of long-term cellular immunity to EBV in pediatric orthotopic liver transplant (OLT) recipients after treatment with the humanized anti-CD20 monoclonal antibody (Rituximab) has not yet been explored. At our institution, one child with EBV-related mononucleosis-like syndrome and five children with polymorphic-EBV-PTLD occurring 6-88 months after OLT were treated with Rituximab. Treatment was well tolerated. All children achieved complete remission. After Rituximab, B-lymphocytes were undetectable in the peripheral blood and EBV-load, monitored with real-time PCR, decreased to undetectable levels in all children from >4000 copies/microg DNA at diagnosis. Four to eight months after Rituximab, EBV-load increased (>4000 copies/microg DNA) in four children, and PTLD recurred in three. Their frequency of EBV-specific T-cell precursors, measured by Elispot analysis, remained lower than in healthy controls. Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve.
Savoldo
Barbara
B
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and the Methodist Hospital, Houston, Texas, USA. bsalvado@bcm.tmc.edu
Rooney
Cliona M
CM
Quiros-Tejeira
Ruben E
RE
Caldwell
Yvette
Y
Wagner
Hans-Joachim
HJ
Lee
Timothy
T
Finegold
Milton J
MJ
Dotti
Gianpietro
G
Heslop
Helen E
HE
Goss
John A
JA
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016031:Liver Transplantation; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D008297:Male; D000069283:Rituximab; D013997:Time Factors
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000069283:Rituximab