Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation: relationship between viral load, EBV-specific T-cell reconstitution and rituximab therapy.
BACKGROUND
Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic stem-cell transplantation markedly improved with quantitative real-time polymerase chain reaction amplification of EBV DNA and visualization of EBV-specific CD8+ T cells with peptide-human leukocyte antigen (HLA) class I tetramers. We decided to combine these methods to evaluate posttransplant EBV reactivation and rituximab therapy.


METHODS
We followed 56 patients treated with an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19), or an unrelated cord-blood transplant (n=5). EBV DNA was quantified in plasma and in peripheral blood mononuclear cells (PBMC). Patient CD8+ T cells were stained with a panel of eight tetramers.


RESULTS
EBV DNA was detected in half of the patients, mainly in the MUD group (17/19). In 19 patients, viral DNA was detected only in the cellular compartment. All patients who controlled reactivation without rituximab and despite a viral load of greater than 500 genome equivalents (gEq)/150,000 PBMC mounted an EBV-specific CD8+ T-cell response in greater than 1.4% of CD3+CD8+ T cells. Plasmatic EBV genome was found in nine patients preceded by a high cellular viral load. Three of these patients controlled the reactivation before or without the introduction of rituximab, and they all developed a significant and increasing EBV-specific T-cell response. Patients with EBV-specific T cells at the onset of reactivation controlled viral reactivation without rituximab.


CONCLUSIONS
This study emphasizes the benefit of an early and close monitoring of EBV reactivation and CD8+-specific immune responses to initiate rituximab only when necessary and before the immune response becomes overwhelmed by the viral burden.
Clave
Emmanuel
E
Laboratoire d'Immunologie et d'Histocompatibilité, Unité INSERM U396, Institut Universitaire d'Hématologie, AP/HP, Hôpital Saint-Louis, Paris, France.
Agbalika
Félix
F
Bajzik
Véronique
V
Peffault de Latour
Régis
R
Trillard
Mélanie
M
Rabian
Claire
C
Scieux
Catherine
C
Devergie
Agnès
A
Socié
Gérard
G
Ribaud
Patricia
P
Adès
Lionel
L
Ferry
Christèle
C
Gluckman
Eliane
E
Charron
Dominique
D
Esperou
Hélène
H
Toubert
Antoine
A
Moins-Teisserenc
Hélène
H
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000628:therapy* / Q000821:virology*; D005312:Fetal Blood / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D019520:Living Donors; D008875:Middle Aged; D011159:Population Surveillance; D011184:Postoperative Period; D000069283:Rituximab; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D019562:Viral Load; D014775:Virus Activation
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab