A single-center experience of retransplantation for liver transplant recipients with a failing graft

With the accumulation of orthotopic liver transplantation (OLT) recipients, an increased number of patients with graft failure need retransplantation (re-OLT). This study was undertaken to examine our clinical experience of re-OLT for patients with poor graft function after primary transplantation at a single center. We analyzed retrospectively, the clinical data of 32 re-OLTs in 31 patients at our center from January 2004 to February 2007, including indications and causes of death, timing of retransplantation, and surgical techniques. The indications included bile leak (2 cases), biliary stricture (16 cases), recurrence of hepatocellular carcinoma (HCC) (5 cases), hepatic artery stenosis (4 cases), hepatic artery thrombosis (HAT) (2 cases), and hepatitis B recurrence (3 cases). The rate of re-OLT was 4.29%. All patients underwent modified piggyback liver transplantations with cadaveric allografts. No intraoperative mortality and acute rejection occurred. Overall, 17 of 31 patients (54.8%) died after re-OLT with survival times ranging from 2 weeks to 28 months. Another 14 patients were cured with survival times of 4 to 32 months. The perioperative mortality rate of patients who underwent re-OLT between 8 and 30 days after their initial transplantation was highest (66.7%). The most common cause of death after re-OLT was sepsis (47.1%), multiple-organ failure (17.6%), and recurrence of HCC (17.6%), whereas the majority of deaths posttransplantation were sepsis-related (54%) within 1 year. Re-OLT is the only therapeutic option for a failing liver graft. Proper indications and optimal operative time, advanced surgical procedures, reasonable individual immunosuppression regimens, and effective perioperative anti-infection treatments contribute to the improved survival of patients after re-OLT.     

肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验

目的  总结肝移植受者移植后淋巴组织增生性疾病（PTLD）的发病情况和诊疗经验。方法  回顾性分析734例肝移植受者的临床资料,收集肝移植受者中PTLD的发病情况、临床症状、实验室数据及影像学资料;分析PTLD受者的病理学结果与治疗方式;分析PTLD受者的预后情况。结果  肝移植受者PTLD发生率为2.2%（16/734）, 中位术后发病时间为8（3, 46）个月。PTLD的临床表现主要为发热、淋巴结肿大,部分出现贫血、肝脾肿大、肝功能异常和消化系统症状等。16例PTLD受者中,1例他克莫司血药浓度异常升高;6例转氨酶升高;14例爱泼斯坦-巴尔病毒（EBV）DNA载量升高;5例巨细胞病毒（CMV）DNA载量升高。13例受者正电子发射计算机体层显像仪（PET/CT）检查提示相关肿大淋巴结¹⁸F-氟代脱氧葡萄糖代谢增高;2例受者颈部及腹部CT检查提示相应区域多发淋巴结肿大;1例受者仅超声提示淋巴结肿大。16例PTLD受者均行病理学检查, 其中13例受者原位杂交结果提示EBV编码的小RNA（EBER）阳性。降低免疫抑制剂水平是PTLD受者的基础治疗方案,根据不同病理类型的PTLD可联合利妥昔单抗靶向治疗及化学药物治疗;针对肿大淋巴结,给予手术及放射治疗。1例受者因PTLD治疗致移植肝衰竭死亡。结论  肝移植术后免疫抑制剂的使用可增加PTLD的患病风险,PTLD在儿童肝移植受者中发生率高于成人,尽早诊断和合理治疗可极大地改善PTLD受者的预后。     

Post-transplant lymphoproliferative disorder (PTLD) presenting as painful lymphocele 12 years after a cadaveric renal transplant

We report a case of post-transplantation lymphoproliferative disorder presenting as a symptomatic lymphocele 12 years after cadaveric renal transplantation for IgA nephropathy. The presentation, imaging, and management are discussed. We review current literature concerning PTLD, post-transplantation lymphoceles, and state-of-the-art imaging techniques.     

Outcomes of kidney retransplantation in recipients with prior post‐transplant lymphoproliferative disorder

Post‐transplant lymphoproliferative disease (PTLD) is an uncommon but serious complication of solid organ transplantation. Reduction in immunosuppression is the mainstay of PTLD treatment, but it may precipitate graft loss. Retransplantation remains controversial, as immunosuppression resumption may trigger PTLD relapse. Herein, we describe the experience of eight patients who underwent kidney retransplantation after successful PTLD treatment. Epstein–Barr virus (EBV) serology was not known before the first transplantation. PTLD was diagnosed 62.5 months (range 5–323 months) after transplantation and was confined to the renal allograft (n = 1), lymph nodes (n = 2), gastrointestinal tract (n = 4), or central nervous system (n = 1). Immunosuppression tapering (8/8), chemotherapy (6/8), oral cavity lymphoma excision (1/8), and allograft nephrectomy (1/8) led to hematological remission in all patients. Retransplantation was performed at a median of 55.5 months (range 29–95   months) after PTLD diagnosis. After a median follow‐up of 62.5 months (range 2–125 months) allograft survival was 87.5% (seven functioning grafts, one failed graft from chronic rejection), with no recurrence of PTLD. In all, five patients remain alive; the other three died from causes other than PTLD. In conclusion, kidney retransplantation appears to be safe in patients with prior PTLD and without major risk of hematological recurrence provided that PTLD has remitted.     

Posttransplant lymphoproliferative disorder in pancreas transplantation: a single-center experience

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a rare, serious complication of transplantation. The characteristics and associations of this disease in pancreas recipients have not been extensively studied. METHODS: From January 1988 through December 2002, 787 pancreas and 569 kidney-pancreas transplants were performed at our institution. Eighteen pancreas recipients developed polymorphic PTLD or malignant lymphoma. Data on clinical course, organ involvement, molecular characteristics, and association with immunosuppression and recent cytomegalovirus (CMV) infection were compiled from the institutional transplant database. Patient survival was compared to recipients of liver and kidney transplants at the same center by using Kaplan-Meier analysis. RESULTS: The 5-year cumulative incidence of PTLD in simultaneous pancreas-kidney, pancreas after kidney, and pancreas transplant alone recipients was 2.5%, 1.2%, and 1.0%, respectively (P = 0.23). A noticeably, but not significantly, higher cumulative incidence was seen in the more recent era since 1995 (2.1% vs. 0.9%, P = 0.15). PTLD in pancreas recipients carried a worse prognosis than in liver or kidney for recipients B-cell, early-onset, and Epstein Barr virus-positive lesions. PTLD was more aggressive in pancreas recipients, with a higher stage at presentation and a trend to more bone marrow involvement. There appeared to be a tendency toward association with recent CMV infection. Since 1995, PTLD recipients have had a lower exposure to antilymphocyte preparations (25 +/- 5 vs. 10 +/- 0.8)(P < 0.05). CONCLUSIONS: PTLD in pancreas recipients remains a rare but aggressive disease, and carries a worse prognosis in comparison to other transplant recipients. These heavily immunosuppressed patients, who often face multiple transplants, may be at greater risk; CMV infection may play an antecedent role.     

Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

Systematic review and meta‐analysis of post‐transplant lymphoproliferative disorder in lung transplant recipients

A systematic review of papers in English on post‐transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random‐effects model, and heterogeneity among studies was quantitated using I² values. Fourteen studies published from 2005 to 2015 were included in the meta‐analysis. One hundred and sixty‐four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67‐fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98‐29.70; P = .003). pOR of death for early onset PTLD (<1 year post‐LT) vs late onset (> 1 year post‐LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20‐1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI ?0.48‐0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08‐2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31‐3.52, P = .94). This meta‐analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.     

Tuberculosis in Iranian kidney transplant recipients: a single-center experience

INTRODUCTION: Renal transplantation recipients are at a high risk of developing tuberculosis (TB) following transplantation, especially in developing countries, with high incidences of morbidity and mortality. In this report, we examined the risk factors and impact of TB on the outcome of kidney transplantation. PATIENTS AND METHODS: Among 1350 living donor Iranian kidney transplantations, 52 (3.9%) had TB diagnosed in various organs. Of these, 7 (13.5%) had TB pretransplantation and 40 (76.9%) were men. The overall mean age was 32.6 +/- 10.5 years. RESULTS: The interval between transplantation and diagnosis was 54.6 +/- 48.23 (range 4 to 140) months. In 34 (65.6%) patients TB was diagnosed after the first year posttransplantation. Pleuro/pulmonary TB was the most common form (68%). All posttransplant TB patients received a quadriple antituberculosis therapy; pyrazinamide, rifampicin, ethambutol, and isoniazide). Hepatotoxicity was seen in 16 (30%) patients, including 12 mild cases with normalization after temporary withdrawal of isoniazide and rifampicin, and four were severe, but mortality was not attributable to hepatocellular failure. Twelve patients (23%) died. Chronic allograft dysfunction occurred in 34 (65%) patients, 19 (37%) with graft loss. Pre-TB patients showed comparable posttransplant courses. CONCLUSION: TB is a common infection among renal transplant recipients in developing countries. The peak incidence is after the first year of transplantation and mortality is considerable. Hepatoxicity is a considerable risk of treatment, possibly as a result of additive toxic effects of immunosuppressive drugs. Chronic allograft nephropathy is a serious complication that has a negative impact on the graft survival.     

Posttransplantation lymphoproliferative disorder in kidney and heart transplant recipients receiving thymoglobulin: a systematic review

Posttransplantation lymphoproliferative disorder (PTLD) is an important complication of transplantation. Risk factors include increased overall immunosuppression exposure and inadequate antiviral prophylaxis; however, the effects of T-cell-depleting agents on PTLD are unclear. A systematic literature review was conducted to assess PTLD in clinical studies published 1999-2009 in transplant patients with ≥3 years follow-up who received Thymoglobulin for induction. Twenty studies were identified (12 kidney, 7 heart, and 1 liver), of which 3 were excluded for insufficient PTLD reporting. The final study group comprised 2,246 kidney and heart transplant recipients (liver study excluded) who received Thymoglobulin. At a median follow-up of 5 years, the incidence of PTLD was 0.98% (kidney, 0.93%; heart, 1.05%) among Thymoglobulin-treated patients. The cumulative Thymoglobulin dose reported in these studies was not associated with the development of PTLD (P = NS). However, incidence of PTLD was significantly lower with antiviral prophylaxis (0.63%) than without (1.87%; P = .013). Heart transplant recipients not receiving antiviral prophylaxis had the highest PTLD incidence, possibly attributable to a greater overall immunosuppressive burden. This analysis revealed that PTLD incidences in kidney and heart transplant recipients receiving Thymoglobulin were low overall and perhaps related more to concomitant anti-viral prophylaxis use.     

Sirolimus immunosuppression in pediatric heart transplant recipients: a single-center experience.

BACKGROUND: Sirolimus has been used in heart transplant recipients for treatment of rejection, alternative immunosuppression (IS) and promotion of regression and prevention of graft vasculopathy (coronary artery disease [CAD]). This study reports on our center's experience with 16 children who underwent heart transplantation. METHODS: Data were obtained by retrospective review. RESULTS: Median age at time of review was 12.3 years (n = 16, 5.1 to 18.0 years; 9 boys, 7 girls), and at time of transplant 7.5 years (6 months to 18.0 years). Median time of sirolimus introduction was 2.7 years (1 month to 8.2 years) post-transplant. Fifteen patients were on steroids, 10 on tacrolimus (FK) and mycophenolate mofetil (MMF), 5 on FK and 1 on MMF with no calcineurin inhibitors (CNIs). The average dose of sirolimus was 0.25 mg/kg or 7.0 mg/m(2) to maintain a target level of 5 to 15 mug/liter. Sirolimus was started for CAD in 6 patients (38%), rejection in 5 (31%), and in 5 with combinations of CNI intolerance, CAD, renal dysfunction and rejection. All 6 who received sirolimus for rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 3A) showed improvement on follow-up biopsies. Two of 3 who received sirolimus for renal dysfunction showed improvement (glomerular filtration rate [GFR] 43 to 67 and 32 to 106 ml/min per 1.73 m(2), respectively). Side effects included hyperlipidemia (38%), abdominal pain (31%), mouth ulcers (26%), anemia or neutropenia (12.5%), persistent pericardial effusion (6%) and interstitial lung disease (6%). Sirolimus therapy was discontinued in 3 patients due to side effects. CONCLUSIONS: In this study sirolimus was found to be a valuable IS agent for the management of rejection, significant renal dysfunction and CNI side effects. These results support the need for prospective studies of the role of sirolimus in primary rejection prophylaxis, primary CAD prophylaxis and CAD regression. There also exists a need to establish an adverse event profile for this drug.     

Long-term survival after cardiac retransplantation: a twenty-year single-center experience

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.     

Infectious complications in kidney transplant recipients: a single-center experience

To determine the patterns of infectious complications in renal transplant recipients in our center, we evaluated 48 patients (29 men and 19 women) who were transplanted between 1994 and 2003. The average age of the patients was 29 years. Thirty (62.5%) and 18 (37.5%) transplants were from living related and cadaveric donors, respectively. Posttransplant immunosuppression consisted of azathioprine or mycophenolate mofetil (MMF), prednisone, antithymocyte globulin (ATG), and cyclosporine or tacrolimus. The acute rejection episodes were treated with pulse doses of methylprednisolone; steroid-resistant rejection was treated with ATG or muromonab (OKT3). All patients received prophylaxis with sulfadoxine-pyrimethamine; none received prophylaxis against cytomegalovirus (CMV) infection. Thirty-nine (81%) recipients developed 77 confirmed episodes of infection; 35 (46%) episodes occurred in the early postoperative period, 28 (36%) in the first month and 14 (18%) after 6 months. According to the type of infection, there were 24 urinary tract, 16 CMV, seven herpetic, nine general septic, six fungal, four pneumonia, one disseminated nocardial, and 10 miscellaneous episodes. All 26 (100%) patients who had acute rejection episodes developed infections compared with 13/22 (59%) who did not have rejection (P < .01). There was a significant correlation between CMV disease and acute rejection and/or tacrolimus or MMF use. CMV infection occurred after the additional immunosuppressive treatment for acute rejection in 10 patients or during the use of tacrolimus or MMF in six patients. We conclude that CMV infection was the most frequent opportunistic pathogen in our renal transplant population and related to the intensive antirejection therapy, followed by urinary tract infections within 3 months after surgery.     

Post-transplantation lymphoproliferative disorder in living-donor liver transplantation: a single-center experience

Background

Post-transplantation lymphoproliferative disorder (PTLD) is a group of life-threatening complications of organ transplantation, which occurs most frequently in pediatric patients. This retrospective study evaluates a single-institution experience of five cases of PTLD after living-donor liver transplantation (LDLT).

Patients and method

We reviewed the records of 78 pediatric patients (<18?years old) and 54 adult patients, who underwent LDLT between July 1991 and December 2009.

Result

PTLD was diagnosed in five pediatric patients, yielding an overall incidence of 3.8%. There were no significant differences between the pediatric patients with and those without PTLD in terms of their age, sex, reason for transplantation, calcineurin inhibitor, Epstein–Barr virus (EBV) serostatus, ABO compatibility, lymphocyte cross-matching, or episodes of biopsy proven rejection. Two patients with abdominal lymphadenopathy and one with gastrointestinal PTLD responded to a reduction in immunosuppression. Treatment with rituximab was necessary for another gastrointestinal PTLD patient. Diffuse large-B-cell lymphoma was diagnosed in one patient with mediastinal and lung masses. This patient was treated with chemotherapy and rituximab, followed by surgical resection. All patients survived and no evidence of recurrence has been found since.

Conclusion

Although PTLD is potentially life-threatening, it can be managed by appropriate and prompt treatment, with a good outcome.     

COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Polyomavirus-associated nephropathy in simultaneous kidney-pancreas transplant recipients: a single-center experience

BACKGROUND: With the introduction of more potent immunosuppressive agents, rejection rates have decreased markedly in simultaneous pancreas-kidney transplant (SPK) recipients. However, with more intense immunosuppression, opportunistic infections such as polyoma virus have been more frequent. The purpose of this article is to outline the clinical course of SPK patients who developed documented polyoma infection in the transplanted kidney. METHODS: A retrospective review of 146 consecutive SPK recipients from 1996 to 2002 was performed. Induction and maintenance immunosuppression, surgical complications, rejection episodes, and opportunistic infections were reviewed. Patients who developed biopsy-proven polyoma virus infection in the renal allograft were identified. RESULTS: Nine patients (6%) were identified who developed polyoma. All had received induction therapy with either OKT3 (5 mg/d for 10.5 days) or thymoglobulin (5.7 mg/kg). Patients without polyoma had received similar induction. Maintenance immunosuppression included Prograf/MMF in six patients, CsA/MMF in two, and CsA/azathioprine in one. Time to diagnosis was an average of 359.3 days (range 136 to 836) after transplantation. Two patients had undergone treatment for kidney rejection prior to the diagnosis of polyoma. Immunosuppression was decreased in all patients when polyoma was identified, and more recently Cidofovir has been administered. Despite these interventions, five of the nine lost kidney function (creatinine > 5.0 or resumption of dialysis). However, none of the nine developed pancreatic abnormalities as demonstrated by normal blood glucose and amylase and no requirement for exogenous insulin. Two patients underwent LRRT more than 1 year after polyoma diagnosis; both have normal kidney function (Cr < 1.5 mg/dL) at 4 years of follow-up. Polyoma virus was the leading cause of renal loss in this cohort of patients. CONCLUSIONS: Polyoma is a serious concern for SPK transplant recipients. The pancreas, however, is spared from clinical evidence of infection, and no rejection was noted when immunosuppression was decreased. These graft losses appear to be a penalty of more potent immunosuppression, and a better treatment strategy is needed to prevent renal graft loss when polyoma is diagnosed. Retransplantation can be considered based on our limited experience.     

Neoplasia in solid organ transplant recipients: single-center experience

The incidence of neoplasms among transplanted patients is increasing, being estimated at between 4% and 18% (mean = 6%). In this article we review the neoplasms in 2514 patients who underwent transplantation in our hospital between 1981 and 2002 including 1579 kidneys, 418 hearts, 430 livers, 70 lungs, and 17 pancreas. We observed 170 tumors in 117 patients. The most frequent neoplasm was skin and lip carcinoma (30 patients) followed by PTLD (18 patients). Our results concur with the literature with one exception, a low incidence of PTLD in heart transplants, which may only be explained due to the use of preventive therapy with antiretroviral drugs.     

Cyclosporine and low-dose ketoconazole in renal transplant recipients: a single-center experience

BACKGROUND: The high cost of cyclosporine A (CsA) is an impediment for low-income patients. Previous studies have used ketoconazole at doses between 200 and 400 mg/day to lower CsA consumption. METHODS: Ketoconazole and CsA were administered prospectively to renal transplant patients. Patients treated historically with CsA were used as a reference group. At different intervals posttransplant, clinical and laboratory data were recorded. RESULTS: The reference group (n=14) was treated with CsA from 1992 to 1997 and the CsA plus ketoconazole group (n=17) from 1998 to 2002. Follow-up was 76+/-22 and 29+/-14 months, respectively. CsA doses throughout the study were 4.0+/-1.3 and 1.6+/-0.6 mg/kg/day (a 60% reduction, P =0.00). Trough levels of CsA were 194+/-87 and 193+/-69 ng/mL, respectively. The ketoconazole dose was 54+/-17 mg/day. The monthly cost of CsA was reduced by 60%, including the cost of ketoconazole. CONCLUSIONS: CsA with ketoconazole resulted in a substantial dose and cost reduction that proved safe and effective.