Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR.
BACKGROUND
Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.


METHODS
During the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by pp65 antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC) plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR.


RESULTS
Using ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/104 PBL (sensitivity, 71.4%; specificity, 89.7%). Twenty seven (90%) of the 30 analyzed patients had active CMV infection and two (6.7%) developed CMV disease. Eleven (40.7%) of these 27 patients had acute GVHD, 18 (66.7%) had opportunistic infection, 5 (18.5%) had chronic rejection and 11 (40.7%) died - one died of CMV disease associated with GVHD and bacterial infection.


CONCLUSIONS
The low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies.
Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, P.O. Box 6111, Zipe Code 13083-970, Campinas, SP, Brazil.
Renata M B
RM
Peres
Cláudia R C
CR
Costa
Paula D
PD
Andrade
Sandra H A
SH
Bonon
Dulcinéia M
DM
Albuquerque
Cristiane
C
de Oliveira
Afonso C
AC
Vigorito
Francisco J P
FJ
Aranha
Cármino A
CA
de Souza
Sandra C B
SC
Costa
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D003586:Cytomegalovirus Infections / Q000175:diagnosis*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012372:ROC Curve; D019562:Viral Load; D055815:Young Adult
D000956:Antigens, Viral; D004279:DNA, Viral