Second Report of the American Intestinal Transplant Working Group: New Insights Into Risk Factors, Treatment...

Intestinal transplantation requires high levels of long-term immunosuppression, putting recipients at high risk of developing malignancies. Factors influencing the incidence and outcomes of these malignancies remain poorly understood.

We conducted a retrospective multicenter study surveying 11 of 15 intestinal transplantation (ITx) centers in the United States, including 336 of 451 transplants performed between 2020 and 2025.

Forty-four patients developed de novo malignancies, including 34 posttransplant lymphoproliferative disorder, 5 skin carcinomas and 5 other carcinomas. Malignancy incidence was 13.1% at a mean follow-up time of 2.33 y. Overall survival did not significantly differ between all intestinal transplant recipients and those who developed malignancies. Malignancy incidence was significantly influenced by maintenance immunosuppression: tacrolimus + Steroids was associated with increased odds of malignancy and tacrolimus + mycophenolate mofetil + steroids with decreased odds. Subsequently reducing immunosuppression did not impact the incidence or severity of rejection. However, concurrent infection-especially opportunistic infection-was associated with higher mortality in the malignancy group.

Malignancy after ITx is likely related to greater T-cell immunosuppression with increased incidence associated with tacrolimus-predominant maintenance regimens and improved outcomes with multimodal regimens and the absence of infections. Our results suggest that reduced T-cell suppression and maintenance of some level of immunocompetence may decrease the incidence, morbidity, and mortality of malignancy after ITx without increasing rejection rates.