Preemptive management of Epstein-Barr virus reactivation after hematopoietic stem-cell transplantation.
BACKGROUND
Epstein-Barr virus (EBV) reactivation after hematopoietic stem-cell transplantation can lead to posttransplant lymphoproliferative disease (PTLD), which carries a high mortality rate. Among therapeutic and prophylactic options being developed, B-cell depletion with monoclonal antibodies is encouraging. Because viral load after transplantation is correlated with PTLD occurrence, we developed a preemptive attitude based on polymerase chain reaction (PCR)-guided rituximab administration.


METHODS
We monitored 115 transplant patients with a quantitative PCR for EBV DNA performed on whole-blood samples. Criteria for treatment initiation were a single PCR above 40,000 DNA genome copies per milliliter (gCop/mL) or two rising values above 10,000 gCop/mL. Weekly rituximab infusion at the dose of 375 mg/m was administered until negative PCR results were available. We evaluated the incidence of EBV reactivation and PTLD development.


RESULTS
Nineteen patients (16.5%) met the criteria for treatment. Incidence of reactivation was the same in high-risk and standard-risk patients (12 vs. 7, P=0.38). One patient developed PTLD after discontinuation of therapy due to a serious adverse event. No other serious adverse events were noticed. Viral load disappeared after a median of three cycles of therapy, and weekly monitoring allowed prompt intervention. No PTLD-related death was observed, all-cause mortality in the treated population was 68%.


CONCLUSIONS
Our PCR-guided and rituximab-based preemptive approach to avoid PTLD after allogeneic hematopoietic stem-cell transplantation is feasible but probably overtreated patients. Prospective trials are strongly needed, they should use uniform PCR techniques and consider higher threshold values for treatment initiation.
Ahmad
Imran
I
Department of Clinical Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. imran.ahmad@bordet.be
Cau
Nguyen V
NV
Kwan
John
J
Maaroufi
Younes
Y
Meuleman
Nathalie
N
Aoun
Mickael
M
Lewalle
Philippe
P
Martiat
Philippe
P
Crokaert
Françoise
F
Bron
Dominique
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000628:therapy; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000601:surgery; D016133:Polymerase Chain Reaction; D000069283:Rituximab; D016019:Survival Analysis; D017741:Survivors; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D007155:Immunologic Factors; D000069283:Rituximab