Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance

Summary

This open-label, proof-of-principle two center cohort study will evaluate the ability of autologous hematopoietic stem cell transplantation to induce tolerance in recipients of deceased or live donor liver transplants (ASCOTT). A maximum of 10 participants will be entered at a minimum of 3 months post liver transplant. The participants will undergo autologous hematopoietic stem cell transplants (HSCT) to "re-educate" their immune systems to accept the graft without the need for long term immunosuppression (tolerance).

Timeline

Start

2015-12

Primary completion

2020-04-30

Completion

2020-04-30

Publications

• Background Sykes M, Levy G. Advances in transplantation. Semin Immunol. 2011 Aug;23(4):222-3. doi: 10.1016/j.smim.2011.08.013. Epub 2011 Sep 22. No abstract available.
• Background Sayegh MH, Carpenter CB. Transplantation 50 years later--progress, challenges, and promises. N Engl J Med. 2004 Dec 23;351(26):2761-6. doi: 10.1056/NEJMon043418. No abstract available.
• Background Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can't live without .. J Immunol. 2013 Dec 15;191(12):5785-91. doi: 10.4049/jimmunol.1390055.
• Background Selzner N, Grant DR, Shalev I, Levy GA. The immunosuppressive pipeline: meeting unmet needs in liver transplantation. Liver Transpl. 2010 Dec;16(12):1359-72. doi: 10.1002/lt.22193.
• Background Kaplan B, Qazi Y, Wellen JR. Strategies for the management of adverse events associated with mTOR inhibitors. Transplant Rev (Orlando). 2014 Jul;28(3):126-33. doi: 10.1016/j.trre.2014.03.002. Epub 2014 Mar 12.
• Background Gotthardt DN, Bruns H, Weiss KH, Schemmer P. Current strategies for immunosuppression following liver transplantation. Langenbecks Arch Surg. 2014 Dec;399(8):981-8. doi: 10.1007/s00423-014-1191-9. Epub 2014 Apr 20.
• Background Sachs DH, Kawai T, Sykes M. Induction of tolerance through mixed chimerism. Cold Spring Harb Perspect Med. 2014 Jan 1;4(1):a015529. doi: 10.1101/cshperspect.a015529.
• Background Kawai T, Sachs DH, Sykes M, Cosimi AB; Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013 May 9;368(19):1850-2. doi: 10.1056/NEJMc1213779. No abstract available.
• Background Xie L, Ichimaru N, Morita M, Chen J, Zhu P, Wang J, Urbanellis P, Shalev I, Nagao S, Sugioka A, Zhong L, Nonomura N, Takahara S, Levy GA, Li XK. Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance. Liver Transpl. 2012 Apr;18(4):444-54. doi: 10.1002/lt.22480.
• Chruscinski A, Juvet S, Moshkelgosha S, Renner E, Lilly L, Selzner N, Bredeson C, Grant D, Adeyi O, Fischer S, Demetris AJ, Zhang J, Epstein M, Macarthur M, Clement AM, Khalili K, Allan D, Altouri S, Bence-Bruckler I, Cattral M, Fulcher J, Galvin Z, Ghanekar A, Greig P, Huebsch L, Humar A, Kew A, Kekre N, Kim TK, McDiarmid S, Martin L, McGilvray I, Sabloff M, Sapisochin G, Selzner M, Smith R, Tinckam K, Yi TJ, Levy G, Atkins H. Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study. Transplantation. 2022 Mar 1;106(3):562-574. doi: 10.1097/TP.0000000000003829.

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Indications