338 Sirolimus rescue maintenance therapy for refractory pancreas rejection
Monday November 16, 2015 from 15:30 to 17:00
Room 110

Nancy A Radke, United States

Sr. Transplant Coordinator


University of Wisconsin Hospital and Clinics


Sirolimus rescue maintenance therapy for refractory pancreas rejection

Nancy Radke1, Dixon B Kaufman2, Hans W Sollinger2, Robert R Redfield2, Jon S Odorico2.

1Nursing, University of WIsconsin Hospital and Clinics, Madison, WI, United States; 2Surgery, Division of Transplantation, University of Wisconsin, Madison, WI, United States

Background: Pancreas allograft rejection episodes have been reported to occur in 10-35% of patients in the first year and account for as many as 6% of early pancreas graft losses.1  Most often, a combination of high dose intravenous corticosteroids (CS) and anti-thymocyte globulin (ATG) are used to treat these rejection episodes.
Whereas there are numerous studies that have evaluated the effectiveness of using sirolimus (SRL) instead of calcineurin inhibitors or mycophenolate sodium (MPA), as maintenance immunosuppressive therapy in pancreas transplantation2, there are few studies using SRL as an adjunct to tacrolimus (TAC) and MPA for maintenance therapy.3,4 Here, we evaluated our experience using SRL in combination with TAC, MPA and CS as rescue therapy for pancreas transplant patients experiencing biopsy proven acute rejection.
Methods: We retrospectively reviewed 802 primary and non-primary deceased donor pancreas transplants performed at our center between 2000-14.  All patients received induction antibody, and maintenance immunosuppressive therapy consisting of TAC, MPA and oral CS.   Of these 802 transplants, we identified 21 pancreas transplant patients (4 SPK, 6 PTA, 11 PAK or PAP) in whom SRL therapy was added for a minimum of 30 days as an additional maintenance immunosuppressive agent, after the patient was diagnosed with biopsy proven acute pancreas rejection. 7 were pancreas retransplants. All patients received 1-2 courses of CS, 7-10 days of ATG and continued TAC therapy; SRL was initiated thereafter for persistently elevated pancreatic enzymes. Patients were dosed to achieve a combined TAC/SRL level of 13-20 ng/ml.
Results: All patient’s pancreatic enzyme levels returned to normal after initiating SRL. By 6 and 12 months after starting sirolimus, actual pancreas graft survival was 90.5% and 85.7% respectively (19/21 at 6 months, 18/21 at 12 months). At 24 months, pancreas graft survival was 66.7% (14/21).  Duration of SRL therapy ranged from 50-1745 days (mean of 415 days). SRL therapy was eventually discontinued in all patients for: ongoing rejection +/- pancreas graft loss (7), worsening renal function or BK nephropathy (4), tapered off electively (4), wound healing problems (3), infection (2), and ovarian cysts (1).
Conclusions:  Sirolimus appears to show benefit for stabilization of refractory pancreas allograft rejection helping preserve pancreas function in 2/3rds of patients 2 years after rejection diagnosis in this series.


[1] Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) cases as reported to the International Pancreas Transplant Registry (IPTR). Clin Transpl. 2008: 45-56
[2] Ciancio G, Sageshima J, Chen L et al. Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single center trial at 10 years. Am J Transplant. 2012.12(12):3363-76
[3] Porubsky M, Gruesser AC, Rana A et al. Excellent outcomes can be achieved in young pancreas transplant alone recipients by addition of sirolimus to maintenance immunosuppression regimen. Transplant Proc. 2014, 46(6):1932-5.
[4] Kandula P, Fridell J, Taber TE et al. Impact of tacrolimus-sirolimus maintenance immunosuppression on proteinuria and kidney function in pancreas transplant alone recipients. Transplantation. 2012, 94(9):940-6.

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