Maintenance immunosuppression with the TOR inhibitor drugs, sirolimus and everolimus, is associated with a significantly reduced risk of developing any posttransplant de novo malignancy and non-skin solid malignancy.
Summary
Post‐transplant de novo malignancies are reviewed in three time periods: (i) the azathioprine (AZA) era from 1962 to 1980–1981, (ii) the cyclosporine (CYA) era (1980 to present) in which the calcineurin inhibitors, CYA and tacrolimus (TAC), were the mainstay of recipient immunosuppression, and (iii) the TOR inhibitor era starting in the year 2000. Both transplant registry and transplant center reports on malignancies occurring in the AZA era are reviewed. Reports from transplant centers and from the Cincinnati Transplant Tumor Registry (CTTR) in both the early CYA era (1980s) and the 1900–2000 CYA era are reported. Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003. The malignancy incidence associated with lymphocyte‐depleting antibody and corticosteroid immunosuppression is discussed. Reduced malignancy incidence recently reported with TOR inhibitors is compared with that of conventional immunosuppression. Important nondrug factors influencing the incidence of post‐transplant malignancies from seven single and three registry reports are detailed. The substantial role that de novo malignancies play in post‐transplant mortality is discussed. Finally, management recommendations for recipients who develop de novo post‐transplant malignancies are briefly presented.
Approximately 2% of deceased donor organ transplants result from donors with a past history of cancer. An analysis of Organ Procurement and Transplantation Network/United Network for Organ Sharing data on 39,455 deceased donors from 2000 to 2005 showed 1069 donors had a PHC, resulting in 2508 transplants, including 1236 kidneys, 891 livers, 199 hearts, 100 lungs, and 82 miscellaneous organs. The most common type of previous cancer in the donor was nonmelanoma skin cancer (n=776) followed by central nervous system malignancies (n=642) and carcinoma of the uterine cervix (n=336). One donor with a glioblastoma multiforme transmitted fatal tumors to three recipients. One donor with a history of melanoma 32 years earlier transmitted a fatal melanoma to a single recipient and, therefore, donors with a history of melanoma should not be used. Donors with a past history of cancer who have a nontraumatic cerebral hemorrhage cause concern because this hemorrhage may be the result of an unrecognized metastatic tumor.
In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, ''variance of practice'' to allow deceased donor, ABO blood group incompatible, A2 antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti-A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A 2 /A 2 B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan-Meier graft survival rates for the B recipients of A 2 /A 2 B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p-value ¼ 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation.
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