Immunosuppression: practice and trends

Similar Results With Solitary Pancreas Transplantation Compared With Simultaneous Pancreas–Kidney Transplantation in the New Millennium

Invasive Aspergillosis (IA) is a rare but life-threatening fungal infection in immunocompromised hosts, including solid organ transplant (SOT) recipients. While extensively studied in other SOT populations, data on IA in pancreas transplant (PT) recipients are limited. Earlier studies reported mortality rates nearing 100%, whereas more recent data show that 12-week mortality still exceeds 20% despite improvements in antifungal therapy. Current prophylaxis strategies for PT recipients mainly focus on Candida species, and there are no clear, standardized recommendations for Aspergillus prevention. Given the paucity of focused data, the epidemiology, clinical characteristics, and outcomes of IA in PT recipients are not well defined. This study aimed to assess the incidence, clinical characteristics, and outcomes of IA among hospitalized PT patients using a nationally representative dataset. We conducted a descriptive analysis using the National Inpatient Sample (NIS) from 2016 to 2020. PT admissions were identified using International Classification of Diseases, Tenth Revision (ICD 10) codes for transplant status and procedures. IA was defined using validated ICD 10 codes. Baseline demographics, hospital characteristics, comorbidities, and outcomes, including sepsis, acute kidney injury (AKI), acute respiratory failure (ARF), invasive mechanical ventilation (IMV), all-cause in-hospital mortality, length of stay, and total hospitalization costs and charges were compared between PT admissions with and without IA. National estimates were calculated using discharge weights, and comparisons were performed using the chi-square test and adjusted Wald test. Multivariable analysis was performed to identify predictors of all-cause in-hospital mortality among PT admissions complicated by IA. Two-sided p values < 0.05 were considered statistically significant. Between 2016 and 2020, 65,980 PT-related hospitalizations were identified, of which 250 (0.4%) had IA. PT admissions complicated by IA were more commonly aged 41 to 60 years (59% vs. 46%, p = 0.012) and were less likely to have a Charlson Comorbidity Index greater than 3 (54% vs. 68.6%, p < 0.001) compared with PT hospitalizations without IA. The PT with the IA cohort had higher rates of sepsis (100% vs. 46.1%, p < 0.001), AKI (60% vs. 36.7%, p < 0.001), ARF (28% vs. 9.4%, p < 0.001), and IMV use (18% vs. 4%, p < 0.001) compared with the PT without the IA cohort. Among PT hospitalizations with IA, IMV use was independently associated with higher all-cause in-hospital mortality (adjusted odds ratio 48.777, p = 0.009). Overall, in-hospital mortality was significantly higher in PT hospitalizations with IA compared with those without IA (12% vs. 2%, p < 0.001). Mean length of stay was longer (24.86 vs. 6.13 days, p < 0.001), and total charges ($378,494 vs. $94,938, p < 0.001), and total costs ($93,019 vs. $24,463, p = 0.023) were significantly higher compared with PT hospitalizations without IA. Although rare, IA in PT recipients is associated with higher rates of sepsis, AKI, ARF, venous thromboembolism, prolonged hospitalization, increased mortality, and greater healthcare utilization. Despite the inherent limitations of administrative datasets, this nationally representative analysis highlights the substantial clinical and economic burden of IA in this high-risk population. These findings emphasize the need for targeted surveillance, early diagnosis, and evidence-based antifungal strategies in this vulnerable population.

Do we still need to demonstrate the survival benefit of pancreas transplantation?

Evaluation of Herpes Simplex Virus Infection Morbidity and Mortality in Pancreas and Kidney-Pancreas Transplant Recipients

The Use of Daclizumab, Tacrolimus and Mycophenolate Mofetil in African‐American and Hispanic First Renal Transplant Recipients

P411 Aims: Induction therapy with RATG is effective in preventing acute rejection in pancreas transplantation and has replaced OKT3 for induction therapy at most centers. T-cell depletion is more prolonged with RATG than OKT3 and the long-term effects of this have not been fully studied. We changed our pancreas protocol in 6/99 with the availability of RATG. In this study, we evaluate the 3-year outcomes (rejection rates, graft survival, patient survival, current maintenance immunosuppressive therapy) of pancreas transplant recipients who received RATG induction therapy and compare them to pancreas transplant recipients who received OKT3 induction therapy. Methods: A retrospective, single-center analysis was preformed of 37 pancreas transplant recipients who received RATG induction therapy between 6/99 and 12/99 compared to 52 pancreas transplant who received OKT3 induction between 1/98 and 6/99. All patients received tacrolimus (FK506), mycophenolate mofetil (MMF) and prednisone maintenance therapy. Median follow-up was no different between groups (4.18±1.3 yrs RATG vs. 4.67±1.7 yrs. OKT3). Results: Rejection rates (RR) and graft survival were similar in both groups at 1-year and 3-year post-transplant. Rejections occurring after 1-year post-transplant in the RATG-group were mostly (43%) due to noncompliance. Mean doses of FK506, MMF and prednisone were not significantly different between groups at 1-,2- or 3-year post transplant. FK506 levels were significantly higher at 1-year post transplant in the OKT3 group (13.1±4.6 ng/mL OKT3 vs. 10.5±3.4 ng/mL RATG, p=0.01) but were no different at 2- or 3-yrs. post-transplant. Mean ± Standard Deviation The average cost of a 7-day course of RATG therapy ($3873) in this study was lower than the cost of OKT3 therapy at an average dose of 35 mg/10 days ($4200) not including the cost of CD3 monitoring. The median length of stay (LOS) for the initial hospitalization was 10±1.5 days in the RATG group compared to 12±1.6 days in the OKT3 group (p=0.32). CMV infections occurred in 13.5% of RATG-induced patients compared to 19.2% of OKT3-induced patients (p=0.48). Conclusions: Pancreas transplants receiving RATG induction therapy with FK506, MMF and prednisone maintenance immunosuppression experienced comparable outcomes to those treated with OKT3 induction therapy with no increase in CMV infections. RATG induction therapy was less expensive than OKT3 with a decreased median LOS in the RATG group.FigureFigure

Long-Term Outcomes of Pancreas After Kidney Transplantation in Small Centers: Is It Justified?

Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

PurposePancreas transplantation (PT) is a definitive treatment for diabetes mellitus (DM), restoring endogenous insulin secretion and improving glycemic control. Despite its efficacy, PT is less common in South Korea compared to Western nations. This study aims to report the clinical outcomes of PT over 2 decades at a single center, focusing on surgical techniques, complications, and graft survival.MethodsA retrospective analysis of 69 PT recipients at Seoul National University Hospital between January 2002 and December 2023 was conducted. Data on recipient and donor demographics, surgical details, immunosuppressive regimens, and graft outcomes were collected. Graft survival was evaluated using Kaplan-Meier analysis, with subgroup comparisons using the log-rank test. Graft failure was defined as graft removal, PT re-registration, insulin dependence exceeding 0.5 units/kg/day for more than 90 days, or patient death.ResultsAmong the 69 recipients, 50 (72.5%) had type 1 DM, and 18 (26.1%) had type 2 DM. Simultaneous pancreas-kidney (SPK) transplantations comprised 84.1% (n = 58), and pancreas-after-kidney (PAK) transplantations accounted for 10.1%. The 1-year and 5-year death-censored pancreas graft survival rates were 92.7% and 89.6%, respectively, with no significant difference between SPK and PAK (P = 0.330). Graft failure occurred in 10 patients, primarily due to pancreatitis and rejection. Donor-related factors, particularly anoxic brain injury, were significantly associated with lower graft survival (P = 0.045).ConclusionPT outcomes in this cohort align with international standards, emphasizing the importance of donor selection and tailored immunosuppression. Expanding PT indications to include selective type 2 DM patients could benefit South Korea’s PT programs with adequate resource allocation.

691 Antilymphocyte induction with either OKT3 or ATGAM has been the standard practice in simultaneous kidney-pancreas transplantation (SKPT) in the U.S. Although the addition of antilymphocyte agents provides enhanced immunosuppression in the early post transplant period, it is associated with additional costs and adverse reactions. The introduction of potent immunosuppressive agents such as Tacrolimus (TAC) and Mycophenolate Mofetil(MMF) may allow SKPT to be performed without antilymphocyte induction. The purpose of this study was to evaluate the safety and efficacy of TAC, MMF and prednisone immunosuppression without antilymphocyte induction after SKPT. Since September, 1996, we performed 28 consecutive SKPTs without antilymphocyte induction. 20 were performed with portal-enteric and 8 with systemic-bladder drainage. 14 were male and 14 female. The mean recipient age was 39 years (range 27-54) with a mean duration of pretransplant diabetes of 26 yrs. Four patients had previous transplants. 14 patients were on dialysis at the time of transplant (PD 9 pts, hemo 5 pts). Mean HLA match was 1.1. Peak PRA was >50% in 2 patients. Mean waiting time for SKPT was 177 days (range 9-621). The first 10 patients received IV TAC for 2-5 days to ensure early therapeutic levels. Target 12 hour trough TAC levels for the first 3 months after SKPT were 15-20 ng/ml. The starting MMF dose was 2 gm/day and steroids were tapered according to protocol. All patients had primary function of the kidney grafts. Three patients died (massive CVA, sudden cardiac death, and post pancreatectomy). Four pancreas grafts (2 thrombosis, 1 chronic rejection and 1 death) and 3 kidney grafts (2 death and 1 chronic rejection) were lost with a median follow-up of 7.5 months (mean 9 months; range 4-16 months). Six patients (22%) had kidney rejection (5 biopsy proven and requiring antilymphocyte therapy) and 2 patients (8%) had pancreas rejection (both biopsy proven and requiring antilymphocyte therapy). The overall incidence of rejection was 25% and only 1 patient had >1 rejection episode. One kidney and one pancreas (same patient; 4%) were lost from rejection. 39% of patients had UTI and 43% had bacteremia. The incidence of CMV disease and EBV-lymphoma were 21% and 4%, respectively. All 25 surviving patients have excellent kidney function and 24 are insulin independent. Patient, kidney, and pancreas graft survival rates are 89%, 89%, and 86%, respectively. Conclusion: TAC, MMF, and prednisone immunosuppression without antilymphocyte induction is safe and effective after SKPT.

Background Fungal infections following pancreas transplantation carry significant morbidity and mortality with an estimated incidence of 3 to 28%. The American Society of Transplantation (AST) suggests considering fluconazole prophylaxis in pancreas transplant recipients (PTR) at high-risk of invasive candidiasis (IC). However, optimal dosage and duration of prophylaxis is unclear. Weekly fluconazole for prevention of IC has been previously reported in liver and bone marrow transplant recipients. We analyzed outcomes of once weekly fluconazole prophylaxis in PTR. Methods We retrospectively reviewed all pancreas transplants performed at our institution from January 2017 through September 2021. PTR at high-risk for IC were defined per AST criteria as those with enteric drainage, vascular thrombosis, and post-perfusion pancreatitis. Patients received once weekly oral fluconazole 200 mg for 12 weeks post-transplant for IC prophylaxis. We analyzed incidence of breakthrough IC within the first 6 months post-transplant. Results We identified a total of 22 PTR, all of whom received simultaneous kidney transplantation from deceased donors. Of these, 12/22 (55%) were male and 11/22 (50%) were African American. Median age at the time of transplantation was 39 years (IQR 34-46). The most common indication for transplantation was type 1 diabetes mellitus (17/22, 21%) with associated nephropathy. No donor organ cultures were positive for fungi and all pancreas transplants were performed using enteric drainage. Notably, one patient developed pancreas allograft thrombosis while another developed pancreatitis. No patients required early discontinuation of fluconazole due to intolerance or side effects and none developed breakthrough IC within 6 months post-transplant (Table 1). Table 1. Conclusion Weekly fluconazole prophylaxis has not been previously studied in PTR. In our cohort, this approach was well tolerated, with no cases of IC at 6 months post-transplantation in patients at high-risk. Randomized controlled clinical trials are needed to define the optimal strategy in this population. Disclosures M. Rizwan Sohail, MD, Aziyo Biologics: Honoraria|Boston Scientific Corporation: Honoraria|Medtronic: Grant/Research Support|TRYX: Grant/Research Support.

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008. Kaplan-Meier survival and multivariate Cox regression analyses were performed using the time interval between kidney and pancreas transplantation either as a categorical (less than one yr, between one and less than three yr, and greater than or equal to three yr) or as a continuous variable (months) to assess kidney graft and patient survival. Patients who received a pancreas transplant three yr or later after kidney transplantation had higher risk of death-censored kidney graft loss (HR 1.56, 95% CI 1.04, 2.32, p = 0.03). Each month beyond three yr between kidney and pancreas transplantation incurred 1% higher risk of subsequent death-censored kidney graft loss (HR 1.01, 95% CI 1.001, 1.02, p = 0.03). In conclusion, time interval between pancreas and kidney transplantation is an independent risk factor of kidney graft loss following pancreas transplantation. Shortening the time interval between pancreas and kidney transplantation to less than three yr may reduce the risk of kidney graft loss in qualified PAK transplant candidates.

Serum Sickness After Treatment With Rabbit Antithymocyte Globulin in a Heart Transplant Recipient With Previous Rabbit Exposure

Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3months to lifelong, depending on organ group) in SOT programs. We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program. Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204days post transplant). Of those who had received 6months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778days, respectively. Late onset PCP occurred in lung recipients who had received 12months of prophylaxis (lung 645-1414days, heart/lung 1583days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP. Our experience with late PCP cases in lung transplant recipients receiving only 1year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.

With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P=0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P<0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P=0.002), cytomegalovirus infection posttransplant (RR=2.41, P=0.001), a retransplant (versus primary transplant) (RR=2.27, P=0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P=0.04). As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.