Shelly Lichtenberg1,2, Ruth Rahamimov3,4,5, Hefziba Green3,4, Benjamin D Fox4,6, Eytan Mor4,5, Uzi Gafter4, Avry Chagnac3,4, Benaya Rozen-Zvi3,4. 1. Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel. shelly_licht@yahoo.com. 2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. shelly_licht@yahoo.com. 3. Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel. 4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Department of Organ Transplantation, Rabin Medical Center, Petah Tikva, Israel. 6. The Pulmonary Institute, Rabin Medical Center, Petah Tikva, Israel.
Abstract
PURPOSE: Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. METHODS: We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. RESULTS: Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. CONCLUSION: Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.
PURPOSE: Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. METHODS: We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. RESULTS: Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. CONCLUSION: Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.
Authors: Andrea K Viecelli; Wai H Lim; Petra Macaskill; Jeremy R Chapman; Jonathan C Craig; Philip Clayton; Solomon Cohney; Robert Carroll; Germaine Wong Journal: Transplantation Date: 2015-12 Impact factor: 4.939
Authors: C Carenco; E Assenat; S Faure; Y Duny; G Danan; M Bismuth; A Herrero; B Jung; J Ursic-Bedoya; S Jaber; D Larrey; F Navarro; G-P Pageaux Journal: Am J Transplant Date: 2015-02-03 Impact factor: 8.086
Authors: A J Matas; K J Gillingham; A Humar; R Kandaswamy; D E R Sutherland; W D Payne; T B Dunn; J S Najarian Journal: Am J Transplant Date: 2008-11 Impact factor: 8.086
Authors: Eric A Engels; Ruth M Pfeiffer; Joseph F Fraumeni; Bertram L Kasiske; Ajay K Israni; Jon J Snyder; Robert A Wolfe; Nathan P Goodrich; A Rana Bayakly; Christina A Clarke; Glenn Copeland; Jack L Finch; Mary Lou Fleissner; Marc T Goodman; Amy Kahn; Lori Koch; Charles F Lynch; Margaret M Madeleine; Karen Pawlish; Chandrika Rao; Melanie A Williams; David Castenson; Michael Curry; Ruth Parsons; Gregory Fant; Monica Lin Journal: JAMA Date: 2011-11-02 Impact factor: 157.335