DOI: 10.1097/tp.0000000000005774 ISSN: 0041-1337

Second Report of the American Intestinal Transplant Working Group: New Insights Into Risk Factors, Treatment Regimens, and Outcomes of Malignancy After Intestinal Transplantation

C. E. Nicole Chiu, Masato Fujiki, Ronald Truong, Juliana M. Marquez, Robert Venick, Susan Feist, Syed-Mohammed Jafri, Razan Aburumman, Pierpaolo Di Cocco, Maria Jimena Alaniz, Jonathan Merola, Jennifer Garcia, Gennaro Selvaggi, Shaheed Merani, Alex Farell, Ruy J. Cruz, Armando Ganoza, George Mazariegos, Debra Sudan, Maria Cristina Segovia, Valberto Sanha, Alexander Kroemer, Cal Matsumoto, Carmel Alemayehu, Digvijay Patil, Vinona Muralidaran, Eric Pahl, Joshua Weiner

Background.

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.

Methods.

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.

Results.

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.

Conclusions.

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.

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