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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0210.
Submitted February 8, 2002
Accepted April 16, 2002
Successful treatment of post-transplant lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8+ T-cell restoration
Pierluigi Porcu, Charles F Eisenbeis, Ronald P Pelletier, Elizabeth A Davies, Robert A Baiocchi, Sameek Roychowdhury, Srinivas Vourganti, Gerard J Nuovo, William L Marsh, Amy K Ferketich, Mitchell L Henry, Ronald M Ferguson, and Michael A Caligiuri*
Department of Medicine, The Ohio State University, Columbus, OH, USA
Department of Surgery, The Ohio State University, Columbus, OH, USA
Department of Pathology, The Ohio State University, Columbus, OH, USA
Center for Biostatistics, The Ohio State University, Columbus, OH, USA
Department of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
* Corresponding author; email: caligiuri-1{at}medctr.osu.edu.
Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening Epstein-Barr virus (EBV)-associated B cell malignancy occurring in 1-2% of renal transplant patients. Host- and PTLD-related factors determining the likelihood of tumor response following reduction of immune suppression (IS) and antiviral therapy remain largely unknown. Standard therapy for PTLD is not well established. Eleven consecutive renal transplant patients who developed EBV-positive PTLD eight to 94 months after allografting were uniformly treated with acyclovir and IS reduction. All PTLD were EBV-positive diffuse large B-cell lymphomas. Ten patients (91%) obtained a durable complete response (CR), and nine (82%) have remained in continuous CR with a median follow-up of 29 months. Five patients (45%) lost their allograft. Of these, four patients had PTLD affecting the transplanted kidney. Peripheral blood CD8+ T cells increased significantly (p=0.0078) from baseline in eight responders available for analysis. One of two patients whose absolute CD8+ T cell count subsequently dropped to baseline after IS reduction relapsed. The expanded CD8+ T cells from two responders specifically recognized an immunodominant peptide from the EBV lytic gene BZLF-1. Another lytic EBV gene, thymidine kinase, was expressed in all eight PTLD tested. IS reduction and antiviral therapy for PTLD after renal transplantation is a highly successful therapeutic combination, but the risk of graft rejection is significant, particularly in patients with PTLD involving the renal allograft. A sustained expansion of CD8+ T-cells and a cellular immune response to EBV lytic antigens may be important for PTLD clearance in renal transplant patients.
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