Incidence and dynamics of Epstein-Barr virus reactivation after alemtuzumab-based conditioning for allogeneic hematopoietic stem-cell transplantation.
BACKGROUND
Reactivation of Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorder (PTLD) pose a significant risk after T-cell-depleted (TCD) allogeneic hematopoietic stem-cell transplantation (HSCT). The pattern of EBV reactivation in patients receiving allogeneic HSCT, incorporating in vivo or in vitro alemtuzumab as the method of TCD, is not known.


METHODS
Monitoring for EBV DNA was performed by quantitative polymerase chain reaction on whole blood in 111 consecutive adults undergoing HSCT using alemtuzumab-based TCD. Patients with more than 40,000 copies/mL were screened for PTLD, followed by the withdrawal of immunosuppression and a single infusion of rituximab.


RESULTS
The 2-year cumulative incidence of EBV DNAemia was 40.3%. In vivo alemtuzumab was associated with earlier EBV reactivation than in vitro alemtuzumab (100-day incidence 22.7% vs. 2.8%, P=0.006). Eighteen patients (16%) had EBV DNAemia of more than 40,000 copies/mL. In evaluable patients, the initial rate of increase in EBV DNA levels was significantly faster in those who went on to treatment with rituximab than in patients who were left untreated (mean doubling time 3.5 days vs. 4.2 days, P=0.003). Rituximab treatment induced rapid declines in EBV DNA with an average half-life of 1.2+/-0.7 days. Only one patient (0.9%) had histologic confirmation of PTLD and subsequently attained a complete remission with rituximab that persists at 18 months.


CONCLUSIONS
Alemtuzumab-based TCD is associated with a high frequency of EBV reactivation but a low (<1%) risk of PTLD using a strategy of preemptive rituximab therapy.
Carpenter
Ben
B
Department of Haematology, Royal Free Hampstead NHS Trust, London, United Kingdom.
Haque
Tanzina
T
Dimopoulou
Maria
M
Atkinson
Claire
C
Roughton
Michael
M
Grace
Sarah
S
Denovan
Shari
S
Fielding
Adele
A
Kottaridis
Panagiotis D
PD
Griffiths
Paul
P
Mackinnon
Stephen
S
Emery
Vincent
V
Chakraverty
Ronjon
R
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000453:epidemiology; D016016:Proportional Hazards Models; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000379:methods*; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D004279:DNA, Viral; D000074323:Alemtuzumab