2025 Southeastern Residency Conference

Title: Association Between Time-To-Therapeutic Tacrolimus Concentrations and Acute Rejection Following Heart and Kidney Transplant

Authors: Raymond Lin, Kwame Asare, Victoria Burnette

Introduction: Available evidence illustrates that greater time-in-therapeutic range tacrolimus therapy correlates with less acute rejection. There is minimal available evidence demonstrating that faster achievement of therapeutic tacrolimus concentrations is associated with better outcomes in terms of graft rejection and graft loss. Patients are at the highest risk of acute allograft rejection during the first 6 months post-transplant, necessitating more intense immunosuppression early on after transplant. This intense immunosuppression puts patients at risk for opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), cytomegalovirus (CMV), urinary tract infections (UTI), BK virus, etc. Tacrolimus is the first-line calcineurin inhibitor due to superior efficacy compared to cyclosporine. Major adverse events include nephrotoxicity, and neurotoxicity (seizures, tremors, paresthesias, headache, PRES, AMS). The purpose of this study was to evaluate incidence of biopsy proven acute rejection (BPAR) and/or graft failure in patients who achieved therapeutic tacrolimus concentrations <10 days after medication initiation compared to patients who achieved therapeutic tacrolimus concentrations >10 days after medication initiation.

Methods: This study was a single center, retrospective chart review of adult patients admitted to Ascension Saint Thomas Hospital West (ASTHW) for heart and/or kidney transplant who received tacrolimus as part of maintenance immunosuppression between August 1, 2022 and September 1, 2023. Patients who were pregnant or incarcerated were excluded. Patients were divided into two groups based on the time-to-therapeutic range tacrolimus concentrations following treatment initiation: < 10 days or > 10 days. The primary outcome was incidence of  BPAR and/or graft failure <6 months following heart and/or kidney transplantation. Secondary outcomes included incidence of infection, neurotoxicity, nephrotoxicity, and hospital readmission at 6 months post-transplant.

Results: A total of 99 patients were included in our analysis, of whom 48 were stratified into the achieved therapeutic tacrolimus concentrations  <10 days after medication initiation group and 51 into the achieved therapeutic tacrolimus concentrations >10 days after medication initiation group. The primary outcome of BPAR and/or graft failure occurred in 10 (10%) patients, with 4 patients in the <10 days group and 6 patients in the >10 days group (P= 0.74). There were no statistically significant differences between the groups in occurrence of CMV (8% vs. 8%, P> 0.99), UTI (8% vs. 16%, P= 0.359), BK virus (4% vs. 2%, P= 0.61), other treated bacterial, viral, or fungal infections (33% vs. 25%, P= 0.392), tremor (29% vs. 24%, P= 0.524), acute kidney injury (54% vs. 65%, P= 0.286), or readmission at 6 months (33% vs. 33%, P> 0.99).

Conclusion: In this study of kidney and/or heart transplant recipients receiving tacrolimus as maintenance immunosuppression, there were no statistically significant differences in rates of BPAR and/or graft failure, infection, neurotoxicity, nephrotoxicity, or readmission. Future studies evaluating time-to-therapeutic range should consider the varying time-in-therapeutic ranges.

Title: Clinical Outcomes for Recipients of Kidney Transplantation from Hepatitis C Virus-Infected Donors
Authors: Caitlyn Tyus, Sally Sikes, Caroline Gatzke, Victoria Burnette
Objective: To assess allograft survival status at one year post-transplant for recipients of Hepatitis C Virus (HCV) NAT-positive donor kidneys in comparison to those who received kidneys from NAT-negative donors
Self Assessment Question: Does receiving a kidney from an HCV NAT-positive donor affect allograft survival status at one year post-transplant compared to HCV NAT-negative donor kidney recipients?
Background: According to the Organ Procurement and Transplantation Network, over 86% of individuals currently awaiting organ transplantation are specifically in need of a kidney. Despite this high demand, a significant number of potentially life-saving organs have been discarded due to donor Hepatitis C virus (HCV) infection. Since the introduction of direct-acting antivirals (DAAs) in 2014, these treatments have demonstrated to be both safe and effective for managing HCV in patients with chronic kidney disease (CKD) and kidney transplant recipients. Nonetheless, kidneys from HCV-positive donors still faced a 48% increased risk of discard in 2019.
Methods: This study was a single-center retrospective chart review conducted at Ascension Saint Thomas Hospital West (ASTHW) to compare clinical outcomes of deceased-donor kidney transplants from HCV-infected donors versus donors without HCV. The study included patients who received a deceased-donor kidney transplant at ASTHW between November 11, 2020 - October 18, 2023. Patients were included when the following criteria was met: kidney transplant recipient, age ≥18 years at time of transplant. Exclusion criteria included patients with a history of transplant, documentation of  dual-organ transplant, pregnant individuals, and incarcerated patients. The primary outcome was the allograft survival status at one year post-transplant for recipients of NAT-positive donor kidneys in comparison to those who received kidneys from NAT-negative donors. Secondary outcomes included incidence of HCV following transplant, rate of HCV recurrence following DAA therapy, and the utilization of various HCV treatment regimens.
Results:  In total, 350 patients were screened, with 91 meeting inclusion criteria, and 84 available for follow-up at one year post-transplant (42 in the HCV Donor Positive (POS) group and 42 in the HCV Donor Negative (NEG) group). There was no significant difference in allograft survival status at one year post-transplant between groups (p=0.457). Secondary outcomes conveyed that 64% of patients who received HCV NAT(+)  kidneys actually contracted HCV following organ transplantation. The HCV treatment of choice was sofosbuvir-velpatasvir, with glecaprevir-pibrentasvir being utilized in two patients due to the drug interaction between sofosbuvir-velpatasvir and amiodarone. Clearance of HCV was achieved by 85% of patients following initial therapy, two patients (7.5%) reported  HCV breakthrough following clearance, one patient (3.7%) experienced treatment failure, and one patient expired during HCV treatment (unrelated to HCV or treatment). The HCV treatment failure was determined to be caused by medication noncompliance. One of the HCV breakthroughs following clearance patients was due to medication noncompliance, while the other was due to the drug interaction and administration timing between sofosbuvir-velpatasvir and magnesium oxide. The secondary treatment following breakthrough or failure was sofosbuvir-velpatasvir-voxilaprevir. 
Conclusion:  In this study, there was no significant difference in allograft survival between HCV-positive and HCV-negative donor kidney transplant recipients. Interestingly, 36% of patients who received HCV NAT-positive donor kidneys did not contract HCV or require DAA therapy following transplantation; this result was correlated with donor kidneys with HCV NAT-positive but HCV antibody negative results. Limitations of this study included small sample size and inability to represent other HCV treatment regimens. Utilizing HCV-positive donor

Title: Incidence of oral candidiasis post kidney transplant in patients with or without oral nystatin prophylaxis 
Authors: Hannah Green, Alexandra Pyatt, Lindsay Reulbach, Rachel Gustafson, Carlos Zayas, and Alex Ewing 
 
Background: Renal transplant recipients (RTRs) are at increased risk for fungal infections, particularly oral candidiasis (OC), due to maintenance immunosuppression. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend 1-3 months of fungal prophylaxis with oral fluconazole, clotrimazole troches, or nystatin suspension. However, the American Society of Transplantation does not endorse routine Candida prophylaxis. The necessity of fungal prophylaxis is questioned given the low incidence of OC, ease of treatment, and potential non-adherence to nystatin. The purpose of this study aimed to evaluate the incidence of OC within 60 days post-transplant in patients with and without 30-day nystatin prophylaxis. 
 
Methods: A single-center, retrospective study was conducted at Prisma Health Greenville Memorial Hospital in patients 18 years or older who underwent a single renal transplant between July 2023 and January 2024 (with prophylaxis) and February 2024 to August 2024 (without prophylaxis). Exclusion criteria included concomitant use of systemic antifungals, antifungal use within 30 days prior to transplant, a history of OC, or a history of prior transplant or dual organ transplant. The primary outcome was the incidence of OC within the first 60 days post-transplant. Secondary outcomes included the occurrence of esophageal candidiasis (EC), systemic fungal infections, inpatient readmissions for OC, and the duration of OC treatment. 
  
Results: A total of 173 transplant patients were screened and 132 were included in the final analysis with 64 in the without prophylaxis group and 68 in the prophylaxis group. At baseline, more patients in the prophylaxis group were on tacrolimus and mycophenolate maintenance regimens, had steroids withdrawn, and used fewer additional steroids. The incidence of OC was similar between groups, with two cases in each (2.9% vs. 3.1%, p=1.000), all of which were treatable. None of the secondary outcomes were statistically significant, though two cases of EC occurred in the prophylaxis group. Only one patient in the prophylaxis group required readmission for OC, and both OC cases in the without prophylaxis group involved additional steroid use. 
 
Conclusions: The findings of this study demonstrate that the incidence of OC was low and, when it occurs, was easily treatable. There was no statistically or clinically significant difference in OC incidence between the prophylaxis and without prophylaxis groups, despite the latter group being more immunosuppressed. Given the comparable rates of OC between the two groups, nystatin prophylaxis does not appear to be warranted in this transplant population. Therefore, no modifications to current clinical practices are recommended. 

Title: Time to Cytomegalovirus Viremia After Valganciclovir Discontinuation in Intermediate and High-Risk Kidney Transplant Recipients


Authors: Morgan Pickard, Kwame Asare, Caren Azurin, Taylor Nickens


Objective: Duration from valganciclovir discontinuation to cytomegalovirus viremia in intermediate and high-risk kidney transplant recipients


Self Assessment Question: Does valganciclovir discontinuation impact time to CMV viremia in intermediate and high-risk kidney transplant recipients? 


Background: Cytomegalovirus (CMV) infection is the most common opportunistic infection following solid organ transplantation, particularly affecting transplant recipients at intermediate (INT) (recipient positive) and high-risk (donor positive, recipient negative) for CMV reactivation. Reactivation can lead to serious complications such as tissue invasion and increased risk of rejection, opportunistic infection, and mortality. Valganciclovir (VGCV) is guideline approved for prophylaxis in these two groups, but its use can be limited by adverse effects such as leukopenia, which occurs in about 50% of patients. Despite the widespread use of VGCV, there is limited research examining whether the duration from VGCV discontinuation to CMV viremia varies between INT and high-risk kidney transplant recipients. This study aimed to evaluate if there is a difference in the mean duration from VGCV discontinuation to CMV viremia between these two groups.


Methods: This single-center retrospective chart review utilized electronic medical records and organ transplant tracking record (OTTR) software at Ascension Saint Thomas Hospital West (ASTHW), with data collected from March 2018 to April 2024. Kidney transplant recipients were identified via OTTR, and data from INT and high-risk groups were analyzed. Patients were categorized into INT and high-risk groups and screened for eligibility based on inclusion/exclusion criteria. Eligible participants were adults (≥ 18 years) who received a kidney transplant, were at INT or high-risk for CMV, discontinued VGCV, and developed CMV viremia. Exclusion criteria included dual organ transplants, pregnancy, incarceration, and restarting VGCV after rejection. The primary outcome assessed the difference in the mean duration from VGCV discontinuation to CMV viremia between the two groups. Secondary outcomes included rejection rates, readmission, resistant CMV, and bacterial, viral, or fungal infections after CMV viremia.
Results: A total of 202 patients were included, with 147 in the INT-risk and 55 in the high-risk groups. CMV viremia developed in 1 (6%) INT and 6 (43%) high-risk patients following VGCV discontinuation during the prophylactic period (p = 0.018). There were no significant differences in the duration of VGCV discontinuation to CMV viremia (42 vs. 43 days, p = 0.999). Additionally, there were no significant differences between the groups in rejection rates (0% vs. 0%, p = 0.999), readmission rates (100% vs. 50%, p = 0.999), infection rates (0% vs. 0%, p = 0.999), and resistant CMV rates (0% vs. 17%, p = 0.999). However, CMV developed in 37 (25%) INT and 12 (24%) high-risk individuals within 3 months following prophylaxis. The time from VGCV discontinuation to CMV viremia during this time was significant between the groups (56 vs. 36 days, p = 0.021). The average interval between CMV tests was also significant (21 vs. 12 days, p  < 0.0001).


Results: A total of 202 patients were included, with 147 in the INT-risk and 55 in the high-risk groups. CMV viremia developed in 1 (6%) INT and 6 (43%) high-risk patients following VGCV discontinuation during the prophylactic period (p = 0.018). There were no significant differences in the duration of VGCV discontinuation to CMV viremia (42 vs. 43 days, p = 0.999). Additionally, there were no significant differences between the groups in rejection rates (0% vs. 0%, p = 0.999), readmission rates (100% vs. 50%, p = 0.999), infection rates (0% vs. 0%, p = 0.999), and resistant CMV rates (0% vs. 17%, p = 0.999). However, CMV developed in 37 (25%) INT and 12 (24%) high-risk individuals within 3 months following prophylaxis. The time from VGCV discontinuation to CMV viremia during this time was significant between the groups (56 vs. 36 days, p = 0.021). The average interval between CMV tests was also significant (21 vs. 12 days, p  < 0.0001).


Conclusion: No significant differences were found in the time from VGCV discontinuation to CMV viremia, or in rejection, readmission, infection, or resistant CMV rates during the prophylactic period. However, our study found that stopping prophylactic VGCV increases CMV risk, especially in the high-risk group. CMV was common in the first three months post-prophylaxis. We recommend CMV monitoring every 14 days during this period.

Title: Comparative Outcomes of Post-Transplant Cyclophosphamide (PTCy) vs Non-PTCy-Based GVHD Prophylaxis Regimens in Allogeneic Hematopoietic Stem Cell Transplantation


Authors: Gyunash Akibova, Kristen Kilby, Henry Kent Holland, Justin LaPorte, Eva Karam 
 
Objective: This study aims to evaluate the long-term outcomes of PTCy-based GVHD prophylaxis in alloHSCT recipients over a 10-year period at Northside Hospital. The primary objective is to assess chronic GVHD-free relapse-free survival (CGFRFS) in patients receiving PTCy compared to those who did not. Secondary objectives include evaluating overall survival (OS), relapse-free survival (RFS), NRM, and the incidence of acute and chronic GVHD.
 
Background: Graft-versus-host disease (GVHD) is a significant complication following allogeneic hematopoietic stem cell transplantation (alloHSCT), particularly in patients with human leukocyte antigen (HLA)-mismatched or haploidentical donors. Traditional GVHD prophylaxis regimens, such as a calcineurin inhibitor (CI) and methotrexate (MTX), have been effective but are still associated with risks of acute and chronic GVHD, as well as non-relapse mortality (NRM). Post-transplant cyclophosphamide (PTCy) alone or in combination with a CI with or without mycophenolate has emerged as a promising approach for GVHD prophylaxis, showing favorable results in reducing GVHD incidence in alloHSCT recipients. A recent retrospective study at The Blood and Marrow Transplant Program at Northside Hospital suggested the benefits of PTCy beyond haploidentical transplants, prompting further investigation into its long-term outcomes.
 
Methods: This single-center, retrospective chart review will include patients who underwent alloHSCT at Northside Hospital between January 1, 2013, and December 31, 2023. Recipient health records will be identified using a proprietary database to identify patients who received an alloHSCT during the study period. Data will be extracted from electronic health records (Cerner Powerchart®, OncoEMR®) and hospital databases. Patients will be excluded if they are receiving a second alloHSCT. Key data points include patient demographics, HLA disparity, use of PTCy, GVHD incidence, time to GVHD onset, disease relapse, and survival outcomes. 
 
Results: In Progress
 
Conclusion: In Progress