Extended pancreas donor program - the EXPAND study rationale and study protocol

Andrea Proneth, Andreas A Schnitzbauer, Florian Zeman, Johanna R Foerster, Ines Holub, Helmut Arbogast, Wolf O Bechstein, Thomas Becker, Carsten Dietz, Markus Guba, Michael Heise, Sven Jonas, Stephan Kersting, Jürgen Klempnauer, Steffen Manekeller, Volker Müller, Silvio Nadalin, Björn Nashan, Andreas Pascher, Falk Rauchfuss, Michael A Ströhlein, Peter Schemmer, Peter Schenker, Stefan Thorban, Thomas Vogel, Axel O Rahmel, Richard Viebahn, Bernhard Banas, Edward K Geissler, Hans J Schlitt, Stefan A Farkas, Andrea Proneth, Andreas A Schnitzbauer, Florian Zeman, Johanna R Foerster, Ines Holub, Helmut Arbogast, Wolf O Bechstein, Thomas Becker, Carsten Dietz, Markus Guba, Michael Heise, Sven Jonas, Stephan Kersting, Jürgen Klempnauer, Steffen Manekeller, Volker Müller, Silvio Nadalin, Björn Nashan, Andreas Pascher, Falk Rauchfuss, Michael A Ströhlein, Peter Schemmer, Peter Schenker, Stefan Thorban, Thomas Vogel, Axel O Rahmel, Richard Viebahn, Bernhard Banas, Edward K Geissler, Hans J Schlitt, Stefan A Farkas

Abstract

Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.

Methods/design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.

Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.

Trial registration: Trial registered at: NCT01384006.

Figures

Figure 1
Figure 1
Inclusion scheme.

References

    1. Sollinger HW, Odorico JS, Becker YT, D'Alessandro AM, Pirsch JD. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg. 2009;250:618–630.
    1. White SA, Shaw JA, Sutherland DE. Pancreas transplantation. Lancet. 2009;373:1808–1817. doi: 10.1016/S0140-6736(09)60609-7.
    1. Becker BN, Brazy PC, Becker YT, Odorico JS, Pintar TJ, Collins BH, Pirsch JD, Leverson GE, Heisey DM, Sollinger HW. Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease. Kidney Int. 2000;57:2129–2135. doi: 10.1046/j.1523-1755.2000.00064.x.
    1. Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman A, Magee JC, Cibrik D, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B. The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation. 2001;71:82–90. doi: 10.1097/00007890-200101150-00014.
    1. Tyden G, Bolinder J, Solders G, Brattstrom C, Tibell A, Groth CG. Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation. Transplantation. 1999;67:645–648. doi: 10.1097/00007890-199903150-00001.
    1. Ojo AO, Meier-Kriesche HU, Arndorfer JA, Leichtman AB, Magee JC, Cibrik DM, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B. Long-term benefit of kidney-pancreas transplants in type 1 diabetics. Transplant Proc. 2001;33:1670–1672. doi: 10.1016/S0041-1345(00)02635-X.
    1. Biesenbach G, Konigsrainer A, Gross C, Margreiter R. Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas-kidney transplantation in comparison to kidney transplantation alone. Transpl Int. 2005;18:1054–1060. doi: 10.1111/j.1432-2277.2005.00182.x.
    1. Giannarelli R, Coppelli A, Sartini M, Aragona M, Boggi U, Vistoli F, Rizzo G, Del Prato S, Mosca F, Marchetti P. Effects of pancreas-kidney transplantation on diabetic retinopathy. Transpl Int. 2005;18:619–622. doi: 10.1111/j.1432-2277.2005.00108.x.
    1. Koznarova R, Saudek F, Sosna T, Adamec M, Jedinakova T, Boucek P, Bartos V, Lanska V. Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Cell Transplant. 2000;9:903–908.
    1. Kennedy WR, Navarro X, Goetz FC, Sutherland DE, Najarian JS. Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med. 1990;322:1031–1037. doi: 10.1056/NEJM199004123221503.
    1. Loss M, Drewitz KP, Apfelbacher CJ, van Rosmalen MD, Rahmel A, Schlitt HJ, Loss J. Why offered pancreases are refused in the allocation process-a descriptive study using routine data from eurotransplant. Transplantation. 2013;95:1134–1141. doi: 10.1097/TP.0b013e318287d83f.
    1. Vinkers MT, Rahmel AO, Slot MC, Smits JM, Schareck WD. How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors. Transplant Proc. 2008;40:1275–1278. doi: 10.1016/j.transproceed.2008.03.142.
    1. Burke GW 3rd, Kaufman DB, Millis JM, Gaber AO, Johnson CP, Sutherland DE, Punch JD, Kahan BD, Schweitzer E, Langnas A, Perkins J, Scandling J, Concepcion W, Stegall MD, Schulak JA, Gores PF, Benedetti E, Danovitch G, Henning AK, Bartucci MR, Smith S, Fitzsimmons WE. Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results. Transplantation. 2004;77:1269–1275. doi: 10.1097/01.TP.0000123903.12311.36.
    1. Mineo D, Sageshima J, Burke GW, Ricordi C. Minimization and withdrawal of steroids in pancreas and islet transplantation. Transpl Int. 2009;22:20–37. doi: 10.1111/j.1432-2277.2008.00761.x.
    1. Boggi U, Mosca F, Vistoli F, Signori S, Del Chiaro M, Bartolo TV, Amorese G, Coppelli A, Marchetti P, Mariotti R, Rondini L, Del Prato S, Rizzo G. Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage. Transplant Proc. 2005;37:1274–1277. doi: 10.1016/j.transproceed.2005.01.024.
    1. Krieger NR, Odorico JS, Heisey DM, D'Alessandro AM, Knechtle SJ, Pirsch JD, Sollinger HW. Underutilization of pancreas donors. Transplantation. 2003;75:1271–1276. doi: 10.1097/.
    1. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant. 2004;4:2018–2026. doi: 10.1111/j.1600-6143.2004.00667.x.
    1. Nakamura T, Onozato W, Mitomi H, Naito M, Sato T, Ozawa H, Hatate K, Ihara A, Watanabe M. Retrospective, matched case–control study comparing the oncologic outcomes between laparoscopic surgery and open surgery in patients with right-sided colon cancer. Surg Today. 2009;39:1040–1045. doi: 10.1007/s00595-009-4011-z.
    1. Bodingbauer M, Pakrah B, Steininger R, Berlakovich G, Rockenschaub S, Wekerle T, Muehlbacher F. The advantage of allocating kidneys from old cadaveric donors to old recipients: a single-center experience. Clin Transplant. 2006;20:471–475. doi: 10.1111/j.1399-0012.2006.00508.x.
    1. Cohen B, Smits JM, Haase B, Persijn G, Vanrenterghem Y, Frei U. Expanding the donor pool to increase renal transplantation. Nephrol Dial Transplant. 2005;20:34–41. doi: 10.1093/ndt/gfh506.
    1. Watson CJ, Rudge C. Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation. Transpl Int. 2005;18:1388. doi: 10.1111/j.1432-2277.2005.00214.x. author reply 1389.
    1. Ridgway D, Manas D, Shaw J, White S. Preservation of the donor pancreas for whole pancreas and islet transplantation. Clin Transplant. 2010;24:1–19.
    1. Ridgway DM, White SA, Kimber RM, Nicholson ML. Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation. Transpl Int. 2005;18:828–834. doi: 10.1111/j.1432-2277.2005.00144.x.
    1. Muthusamy AS, Vaidya AC, Sinha S, Roy D, Elker DE, Friend PJ. Alemtuzumab induction and steroid-free maintenance immunosuppression in pancreas transplantation. Am J Transplant. 2008;8:2126–2131. doi: 10.1111/j.1600-6143.2008.02373.x.
    1. Salvalaggio PR, Schnitzler MA, Abbott KC, Brennan DC, Irish W, Takemoto SK, Axelrod D, Santos LS, Kocak B, Willoughby L, Lentine KL. Patient and graft survival implications of simultaneous pancreas kidney transplantation from old donors. Am J Transplant. 2007;7:1561–1571. doi: 10.1111/j.1600-6143.2007.01818.x.
    1. Andreoni KA, Brayman KL, Guidinger MK, Sommers CM, Sung RS. Kidney and pancreas transplantation in the United States, 1996–2005. Am J Transplant. 2007;7:1359–1375. doi: 10.1111/j.1600-6143.2006.01781.x.
    1. Desschans B, Van Gelder F, Van Hees D, de Rocy J, Monbaliu D, Aerts R, Coosemans W, Pirenne J. Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts. Acta Chir Belg. 2008;108:31–34.
    1. Fernandez LA, Di Carlo A, Odorico JS, Leverson GE, Shames BD, Becker YT, Chin LT, Pirsch JD, Knechtle SJ, Foley DP, Sollinger HW, D'Alessandro AM. Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes. Ann Surg. 2005;242:716–723. doi: 10.1097/01.sla.0000186175.84788.50.
    1. Neidlinger NA, Odorico JS, Sollinger HW, Fernandez LA. Can 'extreme' pancreas donors expand the donor pool? Curr Opin Organ Transplant. 2008;13:67–71. doi: 10.1097/MOT.0b013e3282f44a51.
    1. Singh RP, Rogers J, Farney AC, Moore PS, Hartmann EL, Reeves-Daniel A, Adams PL, Gautreaux M, Stratta RJ. Outcomes of extended donors in pancreatic transplantation with portal-enteric drainage. Transplant Proc. 2008;40:502–505. doi: 10.1016/j.transproceed.2008.02.014.
    1. Barth RN, Janus CA, Lillesand CA, Radke NA, Pirsch JD, Becker BN, Fernandez LA, Thomas Chin L, Becker YT, Odorico JS, D'Alessandro AM, Sollinger HW, Knechtle SJ. Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transpl Int. 2006;19:885–892. doi: 10.1111/j.1432-2277.2006.00388.x.
    1. Boggi U, Vistoli F, Signori S, Del Chiaro M, Amorese G, Vanadia Bartolo T, Croce C, Sgambelluri F, Marchetti P, Mosca F. Outcome of 118 pancreas transplants with retroperitoneal portal-enteric drainage. Transplant Proc. 2005;37:2648–2650. doi: 10.1016/j.transproceed.2005.06.081.
    1. Schadde E, D'Alessandro AM, Knechtle SJ, Odorico J, Becker Y, Pirsch J, Sollinger H, Fernandez LA. Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death. Transpl Int. 2008;21:625–636. doi: 10.1111/j.1432-2277.2008.00642.x.
    1. Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transplant. 2005;19:433–455. doi: 10.1111/j.1399-0012.2005.00378.x.
    1. Schenker P, Vonend O, Ertas N, Wunsch A, Viebahn R. Preprocurement pancreas allocation suitability score does not correlate with long-term pancreas graft survival. Transplant Proc. 2010;42:178–180. doi: 10.1016/j.transproceed.2009.12.036.
    1. Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transpl. 2005;4:433–455.
    1. Stegall MD, Dean PG, Sung R, Guidinger MK, McBride MA, Sommers C, Basadonna G, Stock PG, Leichtman AB. The rationale for the new deceased donor pancreas allocation schema. Transplantation. 2007;83:1156–1161. doi: 10.1097/01.tp.0000261104.27113.05.

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