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Adoptive immunotherapy with allogeneic EBV CTL for organ transplant patients with ebv induced lymphoproliferative disease

Publication ,  Journal Article
Sun, Q; Burton, RL; Ship, AM; Vaughan, WP; Salzman, DE; Lopez, R; Carabasi, MA; Pohlman, B; Lucas, KG
Published in: Blood
December 1, 2000

Epstein Barr virus (EBV) induced lymphoproliferative disease (EBV-LPD) following organ transplantation is a complex disorder, ranging from polyclonal lymphoproliferations to monoclonal lymphomas. While decreasing or discontinuing immunosuppression has been shown to result in regression of disease in many patients, for those with more aggressive disorders, EBV-LPD can be fatal. Adoptive immunotherapy with EBV specific cytotoxic T cells (CTL) is one potential therapy that has been used successfully in stem cell transplant recipients. We have treated two organ transplant patients with EBV-LPD who had persistent disease despite chemo/radiotherapy with allogeneic EBV CTL. Patient I had a large CNS lymphoma following a renal allograft and received three doses of 5 x l O6 CD3+ EBV CTIV kg from his HLA 4/6 antigen matched father. This patient had detectable increases in levels of EBV specific CTL at intervals following each infusion and is now in remission six months following the last CTL infusion. Patient 2 developed a high grade EBV positive B cell (ymphoma involving multiple lymph nodes and bone marrow six years following liver transplantation. Despite multi-agent chemotherapy and subsequent anti-B cell monoclonal antibodies, the patient continued to have a marrow that was diffusely infiltrated with EBV positive B cells. Following three doses of EBV CTL from his HLA 6/6 matched sibling (same schedule as above), this patient had a > 75% reduction of EBV-LPD cells in the bone marrow, with many cells appearing to undergo apoptosis. This patient continues to be clinically well two months post-infusion. Despite clinical/immunologic responses, donor cells were not detected from peripheral blood in either patient. These findings indicate that allogeneic "third party"EBV CTL can be used successfully for patients with EBV-LPD. The role of this form of therapy for other patient groups with EBV-induced malignancies, and the impact of giving chemotherapy prior to CTL to facilitate (at least temporary) engraftment are being investigated.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

December 1, 2000

Volume

96

Issue

11 PART II

Related Subject Headings

  • Immunology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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MLA
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Sun, Q., Burton, R. L., Ship, A. M., Vaughan, W. P., Salzman, D. E., Lopez, R., … Lucas, K. G. (2000). Adoptive immunotherapy with allogeneic EBV CTL for organ transplant patients with ebv induced lymphoproliferative disease. Blood, 96(11 PART II).
Sun, Q., R. L. Burton, A. M. Ship, W. P. Vaughan, D. E. Salzman, R. Lopez, M. A. Carabasi, B. Pohlman, and K. G. Lucas. “Adoptive immunotherapy with allogeneic EBV CTL for organ transplant patients with ebv induced lymphoproliferative disease.” Blood 96, no. 11 PART II (December 1, 2000).
Sun Q, Burton RL, Ship AM, Vaughan WP, Salzman DE, Lopez R, et al. Adoptive immunotherapy with allogeneic EBV CTL for organ transplant patients with ebv induced lymphoproliferative disease. Blood. 2000 Dec 1;96(11 PART II).
Sun Q, Burton RL, Ship AM, Vaughan WP, Salzman DE, Lopez R, Carabasi MA, Pohlman B, Lucas KG. Adoptive immunotherapy with allogeneic EBV CTL for organ transplant patients with ebv induced lymphoproliferative disease. Blood. 2000 Dec 1;96(11 PART II).

Published In

Blood

ISSN

0006-4971

Publication Date

December 1, 2000

Volume

96

Issue

11 PART II

Related Subject Headings

  • Immunology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology