Background: Long-term survival of recipients of solid organ transplants is hampered by chronic rejection, disease recurrence and immunosuppression-induced toxicity. Self-tolerance is re-established after autologous hematopoietic stem cell transplantation (aHSCT) for patients with autoimmune disease. We are testing whether aHSCT can induce tolerance in liver transplant recipients.

Methods: Patients with autoimmune liver disease treated with liver transplantation who are > 3 months post-transplant and 18 to 55 yrs old were eligible for the trial. Hematopoietic stem cells were mobilized and cryopreserved using CD34 cell immunomagnetic selection. Busulfan, cyclophosphamide and rabbit αntithymocyte globulin were administered to ablate auto- and allo-reactivity followed by aHSCT. Immunosuppressive medications were discontinued at the time of aHSCT and everolimus was to be given to expand regulatory T cells for the first 6 months. Patients were followed for evidence of tolerance or rejection.

Results: 75 liver transplant patients were screened, 13 pts were evaluated. One pt declined participation, liver disease was too advanced in 4 pts and too mild in 2 pts. 6 pts were enrolled and 5 have undergone HSCT. All pts had evidence of recurrent primary sclerosing cholangitis (PSC) with moderate to severe ductopenia and fibrosis at a median of 98 months (15-233 mo.) prior to HSCT. The median age was 40 (36-44) yrs. 4 pts were male, 3 pts received living and 2 pts received cadaveric liver grafts and 1 pt had two liver transplants. 4 pts had ulcerative colitis (UC). Pts received a mean 7.21×10⁶ purified CD34/kg. Grade 3-4 non-hematologic toxicity was seen in all patients. Immunosuppression was discontinued in all 5 patients: 2 are alive at 406 and 518 days after HSCT and one died at 212 days post-HSCT of heart failure. One patient developed liver decompensation due to veno-occlusive disease and was re-transplanted 166 days post-HSCT, and one patient died 87 days post HSCT of hemophagocytosis.

Conclusion: These results suggest that while aHSCT can induce tolerance in liver transplant recipients, toxicity is a significant problem that needs to be addressed.

CITATION INFORMATION: Chruscinski A., Atkins H., Macarthur M., Anne Marie C., Grant D., Bredsen C., Renner E., Lilly L., Selzner N., Adeyi O., Smith R., Moshkelgosha S., Humar A., Juvet S., Levy G. An Open-Label Proof-of-Principle Phase 2a Study to Evaluate Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance (ASCOTT) Am J Transplant. 2017;17 (suppl 3).

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