4.3 Article

Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder

Journal

CLINICAL TRANSPLANTATION
Volume 17, Issue 5, Pages 417-422

Publisher

WILEY
DOI: 10.1034/j.1399-0012.2003.00054.x

Keywords

lymphoproliferative disorder; Rituximab therapy; transplantation

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Introduction: Post-transplant lymphoproliferative disorders (PTLD) is a consequence of Epstein - Barr virus (EBV) infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The treatment of PTLD includes reduction/withdrawal of immunosuppression and chemotherapy. This study reports our center experience with humanized monoclonal antibody against CD-20 ( Rituximab) for the treatment of PTLD. Material and methods: Eight cases of PTLD after solid organ transplantation [ six kidney, one kidney/pancreas (KP) and one liver] occurred between September 1998 and October 2001. The mean time between transplant and the diagnosis of PTLD was 57.3 months ( range 3 months to 10 yr). Five patients underwent cadaveric transplant, five males and six were Caucasians with mean age of 48 yr ( range 20 - 67 yr). Results: The clinical presentation was as follows: lymphadenopathy-5, gastrointestinal bleeding-2 and tonsillar enlargement-1. The diagnosis was made by a lymph node biopsy in five, a gastric ulcer biopsy in two and a tonsillar biopsy in one case. Six of them had polymorphous, two had monoclonal B-cell lymphoma, and all were positive for CD-20. Six were related to EBV, documented by latent membrane protein (LMP) or Epstein - Barr encoded RNA ( EBER) staining. Immunosuppression at the time of PTLD diagnosis consisted of tacrolimus in six cases and cyclosporine A (CsA) in two with mycophenolate mofetil (MMF) and azathioprine-3 each and sirolimus-1. Rituximab was administered at a dose of 375 mg/m(2) once a week for 4 wk. There were no side effects seen with this therapy. Immunosuppression was reduced in all patients. Complete remission was observed in seven cases ( one required two courses). One patient who did not respond received chemotherapy. Patients were followed for a mean period of 22.5 months ( range 10 - 45 months post-PTLD diagnosis. At the last follow-up all eight patients were alive, seven with a functioning graft and one on maintenance dialysis. Three of these patients had been in remission for more than 2.5 yr. Conclusion: Rituximab is an effective agent in the treatment of PTLD without the morbidity characteristic of chemotherapy. Chemotherapy should be reserved only for those refractory to Rituximab therapy.

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