EBV PCR in the Diagnosis and Monitoring of Posttransplant Lymphoproliferative Disorder: Results of a Two-Arm Prospective Trial

Abstract

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 diagnos- ing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.

The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases

“…Although EBV DNA qPCR assays are commonly used in the posttransplant setting, [1][2][3][4] no consensus exists with regard to how to use EBV DNA in the blood to diagnose and/or manage EBV 1 PTLD.…”

Posttransplant Lymphoproliferative Diseases During Childhood: Review

“…Ancak yapılan bu analizin spesifisitesi dü-şüktür ve tanısal test olarak bakıldığında gereksiz bir analiz olduğu bildirilmektedir. 82,83 Yüksek riskli bir hastada PTLH düşündüren klinik varlığında, EBV viral yükü yüksek bulunursa, bu takdirde EBV iliş-kili PTLH'de test sonucu anlam kazanmaktadır. En iyi çalışılmış ve en umut veren analiz, T-hücre restorasyonu veya EBV spesifik T-hücre yanıtının analizidir.…”

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

“…However, the whole PCR panel was needed to rule out the presence of EBV-related PTLD. 92 Finally, pre-emptive decisions are very variable between different centers, ranging from more intensive monitoring to reduction of immunosuppression and antiviral therapy to monoclonal anti-CD20 therapy. In order to improve positive predictive value of EBV viremia, some authors propose to combine EBV PCR with measurements of T cell immunity like absolute lymphocyte count (<300/mm³) or the absence of EBV-specific CD8-positive cytotoxic T cells.…”