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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0210.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2341-2348
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Successful treatment of posttransplantation 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
From the Division of Hematology/Oncology, Department of
Medicine; Division of Transplantation, Department of Surgery;
Department of Pathology; Center for Biostatistics; and the
Comprehensive Cancer Center, The Ohio State University, Columbus.
Posttransplantation lymphoproliferative disorder (PTLD) is a
life-threatening Epstein-Barr virus (EBV)-associated B-cell malignancy occurring in 1% to 2% of renal transplantation 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 transplantation patients who
developed EBV-positive PTLD 8 to 94 months after allografting were
uniformly treated with acyclovir and IS reduction. All PTLDs were
EBV-positive diffuse large B-cell lymphomas. Ten patients (91%)
obtained a durable complete response (CR), and 9 (82%) have remained
in continuous CR with a median follow-up of 29 months. Five patients
(45%) lost their allograft. Of these, 4 patients had PTLD affecting
the transplanted kidney. Peripheral blood CD8+ T cells
increased significantly (P = .0078) from baseline in 8 responders available for analysis. One of 2 patients whose absolute CD8+ T-cell count subsequently dropped to baseline after IS
reduction relapsed. The expanded CD8+ T cells from 2 responders specifically recognized an immunodominant peptide from the
EBV lytic gene BZLF-1. Another lytic EBV gene, thymidine
kinase, was expressed in all 8 PTLDs 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 transplantation patients.
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