Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation

Similarity to human PTLD and association with a porcine gammaherpesvirus

Christene A. Huang, Yasushi Fuchimoto, Zachary L. Gleit, Thomas Ericsson, Adam Griesemer, Rachel Scheier-Dolberg, Elizabeth Melendy, Hiroshi Kitamura, Jay A. Fishman, Judith A. Ferry, Nancy Lee Harris, Clive Patience, David H. Sachs

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Posttransplantation lymphoproliferative disease (PTLD) is a major complication of current clinical transplantation regimens. The lack of a reproducible large-animal model of PTLD has limited progress in understanding the pathogenesis of and in developing therapy for this clinically important disease. This study found a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic stem cell transplantation and characterized this disease in swine. Two days before allogeneic peripheral blood stem cell transplantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry and histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-cell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine provide a genetically defined large-animal model of PTLD with many characteristics similar to human PTLD. The availability of this reproducible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTLD in the clinical setting.

Original languageEnglish
Pages (from-to)1467-1473
Number of pages7
JournalBlood
Volume97
Issue number5
DOIs
Publication statusPublished - 2001 Mar 1
Externally publishedYes

Fingerprint

Miniature Swine
Cell Transplantation
Swine
Association reactions
Animals
Swine Diseases
Animal Models
Transplantation
Stem cells
Lymph Nodes
Blood
Peripheral Blood Stem Cell Transplantation
Tissue
Palatine Tonsil
Hematopoietic Stem Cell Transplantation
T-cells
Flow cytometry
Immunosuppression
Polymerase chain reaction
Cyclosporine

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation : Similarity to human PTLD and association with a porcine gammaherpesvirus. / Huang, Christene A.; Fuchimoto, Yasushi; Gleit, Zachary L.; Ericsson, Thomas; Griesemer, Adam; Scheier-Dolberg, Rachel; Melendy, Elizabeth; Kitamura, Hiroshi; Fishman, Jay A.; Ferry, Judith A.; Harris, Nancy Lee; Patience, Clive; Sachs, David H.

In: Blood, Vol. 97, No. 5, 01.03.2001, p. 1467-1473.

Research output: Contribution to journalArticle

Huang, CA, Fuchimoto, Y, Gleit, ZL, Ericsson, T, Griesemer, A, Scheier-Dolberg, R, Melendy, E, Kitamura, H, Fishman, JA, Ferry, JA, Harris, NL, Patience, C & Sachs, DH 2001, 'Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: Similarity to human PTLD and association with a porcine gammaherpesvirus', Blood, vol. 97, no. 5, pp. 1467-1473. https://doi.org/10.1182/blood.V97.5.1467
Huang, Christene A. ; Fuchimoto, Yasushi ; Gleit, Zachary L. ; Ericsson, Thomas ; Griesemer, Adam ; Scheier-Dolberg, Rachel ; Melendy, Elizabeth ; Kitamura, Hiroshi ; Fishman, Jay A. ; Ferry, Judith A. ; Harris, Nancy Lee ; Patience, Clive ; Sachs, David H. / Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation : Similarity to human PTLD and association with a porcine gammaherpesvirus. In: Blood. 2001 ; Vol. 97, No. 5. pp. 1467-1473.
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