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Blood, 15 June 2002, Vol. 99, No. 12, pp. 4364-4369
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Prevention of Epstein-Barr virus-lymphoproliferative disease by
molecular monitoring and preemptive rituximab in high-risk
patients after allogeneic stem cell transplantation
Joost W. J. van Esser,
Hubert G. M. Niesters,
Bronno van der Holt,
Ellen Meijer,
Albert D. M. E. Osterhaus,
Jan Willem Gratama,
Leo F. Verdonck,
Bob Löwenberg, and
Jan J. Cornelissen
From the Departments of Hematology, Virology,
Statistics, Clinical and Tumor Immunology, Erasmus Medical
Center/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; and
the Department of Hematology, Utrecht Medical Center, The Netherlands.
Recipients of a partially T-cell-depleted (TCD) allogeneic
stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD,
LPD-mortality, and abrogates viral reactivation in high-risk patients.
We monitored 49 recipients of a TCD allo-SCT weekly for EBV
reactivation by quantitative real-time polymerase chain reaction (PCR).
Preemptive therapy by a single infusion of rituximab was given
to patients with viral reactivation more than or equal to 1000 geq/mL.
Results were compared with an historical control group of patients
retrospectively monitored for EBV reactivation at similar intervals.
There were 17 prospectively monitored patients who showed EBV
reactivation more than or equal to 1000 geq/mL and 15 received
preemptive therapy. Median time to preemptive therapy
was 113 days (range, 41-202 days) after SCT. There were 14 patients who
showed complete response (CR) as characterized by prevention of EBV-LPD
and complete clearance of EBV-DNA from plasma, which was achieved after
a median number of 8 days (range, 1-46 days). One patient progressed to
EBV-LPD despite pre-emptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who
had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this
prospectively followed series to our historical cohort with the same
high-risk profile showed a reduction of EBV-LPD incidence (18% ± 9% versus 49% ± 11%, respectively) and a complete
abrogation of LPD-mortality (0% versus 26% ± 10%, respectively)
(P = .04) at 6 months from EBV-DNA more than or equal to
1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and
preemptive therapy by rituximab improves outcome in patients at
high risk of EBV-LPD.
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