*Purpose: A pancreas transplant provides patients with brittle diabetes the opportunity of good long-term metabolic control. However, it requires long-term immunosuppression with its associated risks including development of PTLD. Although immunosuppressive protocols have become standardized over the last decade, including regular use of antibody induction therapy, reports on the incidence of, and risk factors for, short- and long-term development of PTLD are scarce.

*Methods: To assess the incidence of PTLD 13,287 primary successfully transplanted pancreas transplants (82% SPK, 10% PAK and 8% PTA) were included; transplants were performed between 1/1/2006 and 12/31/2019 and reported to the IPTR/UNOS. Median follow-up time was 68 months. The incidence of PTLD was based on the UNOS reports or information about PTLD leading to graft failure. Description of patient and donor characteristics was generated. To define risk factors for the development of PTLD several multivariable Cox regression models with time dependent variables were established including factors which proved to be significant in the univariate model. Possible risk factors were transplant type, transplant year, recipient and donor age, gender, ethnicity, EBV and CMV serology, HLA mismatch, depleting and non-depleting induction therapy, maintenance immunosuppression, and the treatment of acute rejection episodes of the pancreas and/or kidney.

*Results: A total number of 160 cases of PTLD were identified – in SPK, 110 cases; in PAK, 27; and in PTA, 23. The 1-year (5-year) rate of PTLD were: for SPK, 0.4% (0.9%); for PAK, 0.2% (1.7%): and for PTA, 1.7% (2.3%). The rate in solitary pancreas transplants was significantly higher compared to SPK (p<0.0001), see Figure 1. The EBV serostatus of 76% of the recipients and 80% of the donors was positive. In 12 % of recipients and 13% of donors the EBV serostatus was unknown.

The result of the first cox regression identified solitary pancreas transplant, negative EBV recipient serostatus, male gender, white race, induction therapy with depleting antibodies, and acute rejection treatment as risk factors. No significant impact of the interaction between recipient and donor EBV serology was found. A more detailed analysis is shown in Table 1.

*Conclusions: The rate of PTLD was higher in solitary transplants: they received more immunosuppression than SPK due to their increased immunogenicity. Negative recipient serostatus carried the highest risk for the development of PTLD. Of note, the risk of PTLD was high when Campath or TMG for more than 4 days was given for induction therapy.

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