EBV PCR in the diagnosis and monitoring of posttransplant lymphoproliferative disorder: results of a two-arm prospective trial.
While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population remains unclear. We performed a prospective 2-arm trial utilizing an EBV PCR panel measuring LMP-1, EBER-1 and EBNA-1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD. In Arm A, 1/31 (3%) patients developed a transient plasma EBV load. Thirteen of 31 (42%) had detectable intracellular EBV. In Arm B, 17 (49%) patients were diagnosed with PTLD. Thirteen (76%) had EBV-positive PTLD with 12/13 (92%) having detectable EBV by PCR. The EBV PCR panel had a high sensitivity (92%), specificity (72%), positive predictive value (PPV) (71%) and negative predictive value (NPV) (93%) for diagnosing EBV-positive PTLD and followed patients' clinical course well (p < 0.001). Comparing the individual PCR assays, plasma EBNA PCR was superior with high sensitivity (77%), specificity (100%), PPV (100%) and NPV (86%). We conclude that EBV PCR is a useful test for managing PTLD patients. While plasma EBNA PCR is the best single assay for diagnosing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.
Tsai
D E
DE
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA. detsai@mail.med.upenn.edu
Douglas
L
L
Andreadis
C
C
Vogl
D T
DT
Arnoldi
S
S
Kotloff
R
R
Svoboda
J
J
Bloom
R D
RD
Olthoff
K M
KM
Brozena
S C
SC
Schuster
S J
SJ
Stadtmauer
E A
EA
Robertson
E S
ES
Wasik
M A
MA
Ahya
V N
VN
D000998:Antiviral Agents / Q000627:therapeutic use; D017931:DNA Primers; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000188:drug therapy; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011183:Postoperative Complications / Q000821:virology; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D014763:Viral Matrix Proteins / Q000097:blood / Q000235:genetics
D000998:Antiviral Agents; D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1