Metastatic Donor-derived Malignancies Following Simultaneous Pancreas-kidney Transplant: Three Case Reports and Management Strategies

Abstract

Background. Stopping immunosuppression in a transplant patient with donor-derived malignancy offers the theoretical benefit that reconstitution of the patient’s immune system will allow “rejection” of the malignancy, as the malignancy also originates from allogeneic tissue. However, this option exists with the caveat that the patient’s allograft(s) will likely be rejected too. In simultaneous pancreas-kidney (SPK) recipients, the normal continued functioning and possible absence of malignancy in either the unaffected kidney or pancreas further complicate this decision. Methods. The charts of 3 patients with donor-derived metastatic malignancies after SPK were retrospectively reviewed in detail. We provide treatment and management recommendations based on successful outcomes and a review of the existing literature. Results. Consistent with a broad review of the literature, in all 3 cases, complete immunosuppression cessation, removal of both grafts, and in 1 case treatment with an immune checkpoint inhibitor to augment the immune response was successful. One patient is doing well 1 year after successfully undergoing kidney retransplantation, while a second patient is active on the waitlist for SPK retransplantation after no evidence of metastatic disease for 2 years. Conclusion. The successful management of metastatic donor-derived malignancies requires allograft removal, immunosuppression cessation, and adjuvant therapy that includes occasional use of checkpoint inhibitors to augment the immune response.

Transmission of pancreatic adenocarcinoma by a single multiorgan donor to two kidney transplant recipients: A case report

“…Pancreatic cancer transmission has been reported to the Organ Procurement and Transplant Network (OPTN) as a possible donor-related malignancy in three recipients ( 7 ). Pancreatic tumor transmission has also been described in patients with combined pancreas-kidney transplantation ( 8 , 9 ) and liver transplantation ( 10 ). In addition, in 2003, Gerstenkorn et al described the case of a 56-year-old man who received a kidney from a patient with lymphangitis carcinomatosa of the lung, which was most likely of pancreatic origin.…”

“…Graft nephrectomy and discontinuation of immunosuppression are the most common and successful forms of treatment in the unfortunate event of cancer transmission in kidney transplantation ( 12 , 13 ). Successful treatment of donor-derived metastatic pancreatic tumors has already been described in an algorithm proposed for patients with metastatic disease after kidney/pancreas transplantation ( 9 ). The basis of treatment appears to be cessation of immunosuppression, which allows recovery of the recipient’s immune system that eliminates the donor tumor cells, and must inevitably be followed by nephrectomy of the graft.…”

Donor-derived duodenal adenocarcinoma of a bladder-drained pancreas allograft

“…These have been managed with cessation of immunosuppression, allograft resection and systemic antineoplastic therapy. 5,6 In bladder-drained pancreata, urothelial carcinomas have been noted at the junction of the duodenal mucosa and bladder urothelium. 8 Consistent with OPTN/DTAC events reporting data, 2 these donor-derived cancers have frequently been aggressive with unfavorable outcomes.…”

“…Most reports of donor‐derived malignancies after pancreas transplantation have been pancreatic adenocarcinomas, 5,6 although sarcomas 7 have also been described. These have been managed with cessation of immunosuppression, allograft resection and systemic antineoplastic therapy 5,6 . In bladder‐drained pancreata, urothelial carcinomas have been noted at the junction of the duodenal mucosa and bladder urothelium 8 .…”

“…By 2000, the proportion had shifted to 35% bladder-drained vs. 65% enteric-drained, 4 progressing to less than 10% bladder-drained over the decade prior to this publication. 3 Most reports of donor-derived malignancies after pancreas transplantation have been pancreatic adenocarcinomas, 5,6 although sarcomas 7 have also been described. These have been managed with cessation of immunosuppression, allograft resection and systemic antineoplastic therapy.…”