Epstein-Barr virus-DNA load monitoring late after lung transplantation: a surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression.
BACKGROUND
Posttransplant lymphoproliferative disease (PTLD) is a serious complication after lung transplantation and its relation with Epstein-Barr virus (EBV) is well recognized. It has been postulated that preemptive reduction of immunosuppression guided by EBV-DNA load may lead to a significantly lower incidence of PTLD, because of the reconstitution of T-cell control. In this report, we describe the feasibility of this approach in terms of safety with regard to the risk of acute as well as chronic allograft rejection in 75 lung transplant recipients transplanted between 1990 and 2001 and followed for this study from June 1, 2001 until January 1, 2006.


METHODS
From all patients visiting our outpatient clinic, EBV-DNA load was measured at least twice a year during the study period. In patients with positive results, measurements were repeated every two to four weeks. EBV reactivation was defined as two consecutive EBV-DNA load measurements with a rising trend; with the last measurement exceeding 10.000 copies/mL under stable immunosuppression. In such case, immunosuppression was reduced.


RESULTS
EBV reactivation was observed in 26/75 patients (35%). One (1.5%) of these patients developed PTLD during the study period. Acute rejection, acceleration of chronic allograft rejection, or worse survival were not observed after reduction of immunosuppression.


CONCLUSIONS
Preemptive reduction of immunosuppression after lung transplantation guided by EBV-DNA load appears to be a safe approach for the prevention of PTLD in lung transplant recipients late after transplantation.
Bakker
Nicolaas A
NA
Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
Verschuuren
Erik A M
EA
Erasmus
Michiel E
ME
Hepkema
Bouke G
BG
Veeger
Nic J G M
NJ
Kallenberg
Cees G M
CG
van der Bij
Wim
W
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001989:Bronchiolitis Obliterans / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D002985:Clinical Protocols / Q000592:standards*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors
D015415:Biomarkers; D004279:DNA, Viral; D007166:Immunosuppressive Agents