Prolonged Survival With FK778 (Malononitrilamide) Monotherapy After Small Bowel Transplantation

A Large Animal Study

S. Zonta, M. Alessiani, J. Viganò, M. Doni, M. Bardone, T. Dominioni, M. De Martino, M. Scaglione, E. Vicini, C. Filisetti, A. Biroli, A. Bottazzi, C. Villa, P. Morbini, P. Dionigi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Malononitrilamide 715 (FK778) is a new class of immunosuppressant, derived from the active metabolite of leflunomide A77 1726. We investigated the efficacy of two different immunosuppressive induction protocols with tacrolimus plus FK778 followed by FK778 monotherapy. In a swine model of small bowel transplantation, we observed three groups, divided by different therapy regimens: group 1 (n = 5): no immunosuppressant (control group); group 2 (n = 10): oral tacrolimus (from postoperative day [POD] 0 to 30) and FK778 (from POD 0 to 60); group 3 (n = 8): oral tacrolimus, as group 2, and FK778 (from POD 7 to POD 60). Median survival was 11, 60, and 21 days in groups 1, 2, and 3, respectively. In group 1 all animals died of acute rejection; in group 2 the causes of death were technical complication (n = 1) and sepsis (n = 1); in group 3, one animal died from obstruction, two from pneumonia, one from peritonitis, one from sepsis. Group 2 accounted for 0.5 infection episode/animal versus 0.62 in group 3 (P <.05). Acute rejection was absent or mild in 66% and 75% of group 3 and 2 biopsies, respectively (P <.05). The D-xylose absorption curves from groups 2 and 3 were similar to those of the nontransplanted healthy animals. In conclusion, FK778 monotherapy after a consistent induction period with tacrolimus combined immunosuppression is able to extend survival and preserve optimal absorptive capacity of the small bowel allograft in our pig model. The association of tacrolimus and FK778 from day 1, compared to the delayed administration of FK778 from day 7, results in a significant reduction of infections and postoperative complications.

Original languageEnglish
Pages (from-to)2021-2023
Number of pages3
JournalTransplantation Proceedings
Volume39
Issue number6
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Transplantation
Tacrolimus
Immunosuppressive Agents
leflunomide
A 771726
Sepsis
Swine
2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide
Xylose
Group Psychotherapy
Infection
Peritonitis
Immunosuppression
Allografts
Cause of Death
Pneumonia
Biopsy
Control Groups

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Prolonged Survival With FK778 (Malononitrilamide) Monotherapy After Small Bowel Transplantation : A Large Animal Study. / Zonta, S.; Alessiani, M.; Viganò, J.; Doni, M.; Bardone, M.; Dominioni, T.; De Martino, M.; Scaglione, M.; Vicini, E.; Filisetti, C.; Biroli, A.; Bottazzi, A.; Villa, C.; Morbini, P.; Dionigi, P.

In: Transplantation Proceedings, Vol. 39, No. 6, 07.2007, p. 2021-2023.

Research output: Contribution to journalArticle

Zonta, S. ; Alessiani, M. ; Viganò, J. ; Doni, M. ; Bardone, M. ; Dominioni, T. ; De Martino, M. ; Scaglione, M. ; Vicini, E. ; Filisetti, C. ; Biroli, A. ; Bottazzi, A. ; Villa, C. ; Morbini, P. ; Dionigi, P. / Prolonged Survival With FK778 (Malononitrilamide) Monotherapy After Small Bowel Transplantation : A Large Animal Study. In: Transplantation Proceedings. 2007 ; Vol. 39, No. 6. pp. 2021-2023.
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abstract = "Malononitrilamide 715 (FK778) is a new class of immunosuppressant, derived from the active metabolite of leflunomide A77 1726. We investigated the efficacy of two different immunosuppressive induction protocols with tacrolimus plus FK778 followed by FK778 monotherapy. In a swine model of small bowel transplantation, we observed three groups, divided by different therapy regimens: group 1 (n = 5): no immunosuppressant (control group); group 2 (n = 10): oral tacrolimus (from postoperative day [POD] 0 to 30) and FK778 (from POD 0 to 60); group 3 (n = 8): oral tacrolimus, as group 2, and FK778 (from POD 7 to POD 60). Median survival was 11, 60, and 21 days in groups 1, 2, and 3, respectively. In group 1 all animals died of acute rejection; in group 2 the causes of death were technical complication (n = 1) and sepsis (n = 1); in group 3, one animal died from obstruction, two from pneumonia, one from peritonitis, one from sepsis. Group 2 accounted for 0.5 infection episode/animal versus 0.62 in group 3 (P <.05). Acute rejection was absent or mild in 66{\%} and 75{\%} of group 3 and 2 biopsies, respectively (P <.05). The D-xylose absorption curves from groups 2 and 3 were similar to those of the nontransplanted healthy animals. In conclusion, FK778 monotherapy after a consistent induction period with tacrolimus combined immunosuppression is able to extend survival and preserve optimal absorptive capacity of the small bowel allograft in our pig model. The association of tacrolimus and FK778 from day 1, compared to the delayed administration of FK778 from day 7, results in a significant reduction of infections and postoperative complications.",
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AU - De Martino, M.

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AU - Vicini, E.

AU - Filisetti, C.

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