Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder

Rolf N. Barth, Arthur J. Nam, Matthew G. Stanwix, Debra Kukuruga, Cinthia I. Drachenberg, Rachel Bluebond-Langner, Helen Hui-Chou, Steven T. Shipley, Stephen T. Bartlett, Eduardo D. Rodriguez

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts. METHODS: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques. Tacrolimus monotherapy was administered via continuous intravenous infusion for 28 days then tapered to daily intramuscular doses. RESULTS: Five of the six animals treated with tacrolimus monotherapy demonstrated rejection-free graft survival up to 177 days (mean, 113 days). All animals with prolonged graft survival developed posttransplant lymphoproliferative disorders (PTLD). Three animals converted to rapamycin after 28 days of rejection of their allografts, but did not develop PTLD. Genotypic analysis of PTLD tumors demonstrated donor origin in three of the five analyzed by short-tandem repeats. Sustained alloantibodies were detected in rejecting grafts and absent in nonrejecting grafts. CONCLUSIONS: Tacrolimus monotherapy provided prolonged rejection-free survival of composite facial allografts in a non-human primate model but was associated with the development of a high frequency of donor-derived PTLD tumors. The transplantation of a large volume of vascularized bone marrow in composite tissue allografts may be a risk factor for PTLD development.

Original languageEnglish (US)
Pages (from-to)1242-1250
Number of pages9
JournalTransplantation
Volume88
Issue number11
DOIs
StatePublished - Dec 2009
Externally publishedYes

Fingerprint

Lymphoproliferative Disorders
Primates
Allografts
Vascularized Composite Allotransplantation
Tacrolimus
Graft Survival
Composite Tissue Allografts
Transplants
Isoantibodies
Mixed Lymphocyte Culture Test
Macaca
Organ Transplantation
Sirolimus
Immunosuppressive Agents
Intravenous Infusions
Microsatellite Repeats
Neoplasms
Transplantation
Bone Marrow
Bone and Bones

Keywords

  • Composite tissue allotransplantation
  • Face transplant
  • Non-human primate
  • Posttransplant lymphoproliferative disorder
  • Tacrolimus

ASJC Scopus subject areas

  • Transplantation

Cite this

Barth, R. N., Nam, A. J., Stanwix, M. G., Kukuruga, D., Drachenberg, C. I., Bluebond-Langner, R., ... Rodriguez, E. D. (2009). Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder. Transplantation, 88(11), 1242-1250. https://doi.org/10.1097/TP.0b013e3181c1b6d0

Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder. / Barth, Rolf N.; Nam, Arthur J.; Stanwix, Matthew G.; Kukuruga, Debra; Drachenberg, Cinthia I.; Bluebond-Langner, Rachel; Hui-Chou, Helen; Shipley, Steven T.; Bartlett, Stephen T.; Rodriguez, Eduardo D.

In: Transplantation, Vol. 88, No. 11, 12.2009, p. 1242-1250.

Research output: Contribution to journalArticle

Barth, RN, Nam, AJ, Stanwix, MG, Kukuruga, D, Drachenberg, CI, Bluebond-Langner, R, Hui-Chou, H, Shipley, ST, Bartlett, ST & Rodriguez, ED 2009, 'Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder', Transplantation, vol. 88, no. 11, pp. 1242-1250. https://doi.org/10.1097/TP.0b013e3181c1b6d0
Barth, Rolf N. ; Nam, Arthur J. ; Stanwix, Matthew G. ; Kukuruga, Debra ; Drachenberg, Cinthia I. ; Bluebond-Langner, Rachel ; Hui-Chou, Helen ; Shipley, Steven T. ; Bartlett, Stephen T. ; Rodriguez, Eduardo D. / Prolonged survival of composite facial allografts in non-human primates associated with posttransplant lymphoproliferative disorder. In: Transplantation. 2009 ; Vol. 88, No. 11. pp. 1242-1250.
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abstract = "BACKGROUND: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts. METHODS: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques. Tacrolimus monotherapy was administered via continuous intravenous infusion for 28 days then tapered to daily intramuscular doses. RESULTS: Five of the six animals treated with tacrolimus monotherapy demonstrated rejection-free graft survival up to 177 days (mean, 113 days). All animals with prolonged graft survival developed posttransplant lymphoproliferative disorders (PTLD). Three animals converted to rapamycin after 28 days of rejection of their allografts, but did not develop PTLD. Genotypic analysis of PTLD tumors demonstrated donor origin in three of the five analyzed by short-tandem repeats. Sustained alloantibodies were detected in rejecting grafts and absent in nonrejecting grafts. CONCLUSIONS: Tacrolimus monotherapy provided prolonged rejection-free survival of composite facial allografts in a non-human primate model but was associated with the development of a high frequency of donor-derived PTLD tumors. The transplantation of a large volume of vascularized bone marrow in composite tissue allografts may be a risk factor for PTLD development.",
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AU - Barth, Rolf N.

AU - Nam, Arthur J.

AU - Stanwix, Matthew G.

AU - Kukuruga, Debra

AU - Drachenberg, Cinthia I.

AU - Bluebond-Langner, Rachel

AU - Hui-Chou, Helen

AU - Shipley, Steven T.

AU - Bartlett, Stephen T.

AU - Rodriguez, Eduardo D.

PY - 2009/12

Y1 - 2009/12

N2 - BACKGROUND: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts. METHODS: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques. Tacrolimus monotherapy was administered via continuous intravenous infusion for 28 days then tapered to daily intramuscular doses. RESULTS: Five of the six animals treated with tacrolimus monotherapy demonstrated rejection-free graft survival up to 177 days (mean, 113 days). All animals with prolonged graft survival developed posttransplant lymphoproliferative disorders (PTLD). Three animals converted to rapamycin after 28 days of rejection of their allografts, but did not develop PTLD. Genotypic analysis of PTLD tumors demonstrated donor origin in three of the five analyzed by short-tandem repeats. Sustained alloantibodies were detected in rejecting grafts and absent in nonrejecting grafts. CONCLUSIONS: Tacrolimus monotherapy provided prolonged rejection-free survival of composite facial allografts in a non-human primate model but was associated with the development of a high frequency of donor-derived PTLD tumors. The transplantation of a large volume of vascularized bone marrow in composite tissue allografts may be a risk factor for PTLD development.

AB - BACKGROUND: Composite tissue allotransplantation may have different immunosuppressive requirements and manifest different complications compared with solid organ transplantation. We developed a non-human primate facial composite tissue allotransplantation model to investigate strategies to achieve prolonged graft survival and immunologic responses unique to these allografts. METHODS: Composite facial subunits consisting of skin, muscle, and bone were heterotopically transplanted to mixed lymphocyte reaction-mismatched Cynomolgus macaques. Tacrolimus monotherapy was administered via continuous intravenous infusion for 28 days then tapered to daily intramuscular doses. RESULTS: Five of the six animals treated with tacrolimus monotherapy demonstrated rejection-free graft survival up to 177 days (mean, 113 days). All animals with prolonged graft survival developed posttransplant lymphoproliferative disorders (PTLD). Three animals converted to rapamycin after 28 days of rejection of their allografts, but did not develop PTLD. Genotypic analysis of PTLD tumors demonstrated donor origin in three of the five analyzed by short-tandem repeats. Sustained alloantibodies were detected in rejecting grafts and absent in nonrejecting grafts. CONCLUSIONS: Tacrolimus monotherapy provided prolonged rejection-free survival of composite facial allografts in a non-human primate model but was associated with the development of a high frequency of donor-derived PTLD tumors. The transplantation of a large volume of vascularized bone marrow in composite tissue allografts may be a risk factor for PTLD development.

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