To describe the clinical presentation and management of two patients who developed pancreatic transplant rejection during treatment of post-transplant CNS lymphoma (PT-CNSL).

PT-CNSL is a rare neoplasm developing after immunosuppressive therapy following solid-organ transplantation. Treatment involves reducing immunosuppression, which risks graft rejection. In pancreas transplant recipients, this is associated with increased mortality rates with limited therapeutic alternatives.

Case Description:

Case 1: a 43-year-old female status post pancreas-kidney transplant was diagnosed with PT-CNSL in 2022, initially managed by withholding tacrolimus and initiating rituximab therapy at 375 mg/m2 IV (starting weekly for 3 months, then monthly). The lymphoma regressed with treatment until the patient experienced pancreatic graft rejection (lipase peak 1,124 U/L). This was treated by adding on low-dose tacrolimus which resulted in an improvement in graft rejection and allowed ongoing therapy with rituximab, yielding a complete response of the PT-CNSL.

Case 2: A 55-year-old female status post pancreas-kidney transplant in 2010, was diagnosed with PT-CNSL in 2021. Treatment involved discontinuation of mycophenolate and tacrolimus and initiation of rituximab at 375 mg/m2 IV (starting weekly for six months, then monthly). Although the lymphoma regressed, the patient experienced acute epigastric pain with a lipase peak of 2,715 U/L with CT of the abdomen illustrating acute pancreatitis. Due to concern for transplant rejection, low-dose tacrolimus was initiated along with rituximab, resulting in resolution of elevated lipase. Continued serial neuroimaging studies demonstrated a complete response.

PT-CNSL increases morbidity and mortality in pancreas transplant patients with limited treatment options. Treatment should balance maintaining CNS response with careful re-initiation of  immunosuppression in the setting of graft rejection; however, there is limited knowledge regarding ideal doses of immunosuppression. We demonstrate that low-dose tacrolimus to prevent graft rejection was safe and effective in treating two patients with PT-CNSL, highlighting the need for further investigation into optimal management strategies.