CAR-T therapy in solid organ transplant recipients with treatment refractory posttransplant lymphoproliferative disorder.

Chimeric antigen receptor T cells (CAR-T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor-associated antigen like CD19 in lymphoma. CAR-T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR-T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10-20 years after SOT who received CAR-T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR-T therapy such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR-T therapy. In addition, the PAK patient developed acute pancreatitis after CAR-T therapy. This case series identifies the challenges of using CAR-T therapy to manage refractory PTLD in SOT recipients and its possible complications.

Challenges of Diagnosing Antibody-Mediated Rejection: The Role of Invasive and Non-Invasive Biomarkers.

Kidney transplantation is the best treatment modality for end-stage kidney disease, leading to improvement in a patient's quality and quantity of life. With significant improvements in short-term outcomes, prolonging long-term allograft and patient survival remain ongoing challenges. The ability to monitor allograft function, immune tolerance and predict rejection accurately would enable personalization and better prognostication during post-transplant care. Though kidney biopsy remains the backbone of transplant diagnostics, emerging biomarkers can help detecting kidney allograft injury early enough to prevent permanent damage and detect injury before it is clinically apparent. In this review, we summarize the recent biomarkers that have shown promise in the prediction of acute rejection with a focus on antibody-mediated rejection in kidney transplantation.

Evaluation of a Ureteral Stent Removal Protocol in Adult Kidney Transplant Recipients.

Existing literature on best practices to reduce the risk of infectious complications associated with ureteral stent removal in kidney transplant recipients is limited. Prior to 2021, a formal process surrounding stent removal was not in place at our institution. In June 2021, a stent removal protocol was established. This protocol included the following: obtaining a preprocedure urine culture, prescribing universal culture-directed antimicrobial prophylaxis, earlier stent removal posttransplant, and patient education. We performed a retrospective quasi-experimental study of kidney transplant recipients who had their stents removed between July 2020 and June 2022. The primary outcome was the incidence of infectious complications within 30 days. Infectious complications were defined as urinary tract infection and bacteremia due to urinary source, as well as hospitalization, emergency department visit, or outpatient encounter for possible urinary tract infection. Secondary objectives included infectious and immunologic complications within 30 days to 1 year from transplant. During this study period, 239 adult kidney transplant recipients were included: 88 in the preprotocol group and 151 in the protocol group. The median time to stent removal was shorter in the protocol group (25 vs 36 days, P < .001). More patients in the protocol group received preprocedure antibiotics (99% vs 36%, P < .001). Infectious complications were higher in the preprotocol group (9% vs 3%, P = .035). Overall, the stent removal protocol was associated with fewer infectious complications (odds ratio, 0.18; 95% CI, 0.05-0.73). Further investigation is necessary to determine which individual interventions, if any, drive this benefit.