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Low-Dose Chemotherapy for Epstein-Barr Virus–Positive Post-Transplantation Lymphoproliferative Disease in Children After Solid Organ Transplantation

From the Departments of Pediatrics, Pathology and Microbiology, Surgery, and Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha, NE; Departments of Pediatrics and Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and Department of Pediatrics, Children's Hospital Research Medical Center, Seattle, WA

Address reprint requests to Thomas G. Gross, MD, PhD, Children's Hospital, 700 Children's Dr, Columbus, OH 43205-2696; e-mail: tgross{at}chi.osu.edu

PURPOSE: To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) –positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD.

PATIENTS AND METHODS: Eligible patients received cyclophosphamide (600 mg/m² intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles.

RESULTS: Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively.

CONCLUSION: This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.

Supported by Grant No. R03 CA 78204-01 (T.G.G.) from the National Cancer Institute and Grant No. 6605-01 from the Leukemia and Lymphoma Society (T.C.G., J.C.L., and T.G.G.).

Presented in part at the 3rd Symposium on Immunodeficiencies and Malignancies, Berlin, Germany, February 7-9, 2001; the 44th Annual Meeting of the Society of Hematology, Philadelphia, PA, December 6-10, 2002; and the 1st International Conference on Childhood Non-Hodgkin's Lymphoma, New York, NY, April 10-12, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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