Post-transplant lymphoproliferative disorder (PTLD) is a serious complication resulting in mortality and renal graft failure. PTLD is a heterogeneous disorder, which causes different clinical forms of disease from non-specific viral syndrome to malignant lymphoma and has various etiologies, clinical features, and treatment strategies. Here, we report on a patient who had a PTLD in the hilum of a transplanted kidney at 5 months after renal transplantation. The PTLD resulted in hydronephrosis of the transplanted kidney and graft dysfunction by local urinary tract obstruction. Despite treatment including immunosuppression reduction and rituximab administration, we removed the transplanted kidney from the recipient because the PTLD did not respond to the therapy.
Humans ; Hydronephrosis ; Immunosuppression ; Kidney Transplantation ; Kidney* ; Lymphoma ; Lymphoproliferative Disorders* ; Mortality ; Rituximab ; Transplants ; Urinary Tract*

Lung transplantation is a viable option for patients with chronic obstructive pulmonary disease (COPD), and emphysema is the most common indication to undergo lung transplantation. A total of seven lung and one heart-lung transplantations were performed between July 1996 and June 2004 at the Yongdong Severance Hospital, and herein, three emphysema patients who underwent single lung transplantations are reviewed. There were 2 males and 1 female, with a mean age of 50 years (35, 57 and 58 years). They all underwent an operation, without cardiopulmonary bypass, and there was no operative mortality. The mean survival was 12 months (4 months, 15 months and 17 months) and all succumbed to death due to activation of pulmonary tuberculosis, post-transplantation lymphoproliferative disease and cytomegalovirus (CMV) gastritis associated with asphyxia. Infection was the most common postoperative complication, resulting in longer hospital stays, higher medical expenses and shorter survival rates, necessitating aggressive prophylactic management. The accumulation of experience, modifications to operative procedures and perioperative care may lead to improved early and long- term survival in patients with emphysema undergoing single or bilateral lung transplantations.
Adult ; Aged ; Asphyxia/mortality ; Cytomegalovirus Infections ; Fatal Outcome ; Female ; Gastritis/mortality/virology ; Humans ; *Lung Transplantation ; Lymphoproliferative Disorders/mortality ; Male ; Middle Aged ; Pulmonary Emphysema/*surgery ; Survival Analysis ; Tuberculosis, Pulmonary/mortality

Liver biopsies are used routinely in the assessment of graft dysfunction following liver transplantation and generally considered to be the most reliable method for the diagnosis of posttransplant complications with overlapping clinical and laboratory findings. To investigate posttransplant complications causing graft dysfunction and usefulness of liver biopsy, we analysed clinicopathologic features of 65 posttransplant liver biopsies, 2 autopsies and an explanted liver, taken from 20 patients. The frequencies of posttransplant complications were acute cellular rejection in 9 patients (45%), postoperative infection in 11 patients (55%), of which cytomegalovirus (CMV) infection and systemic invasive aspergillosis with candidiasis occured in 10 patients (50%) and 1 patient (5%), respectively. Remainders were hepatic arterial thrombosis in two (10%), primary graft dysfunction due to fatty donor liver in one (5%), and posttransplant lymphoproliferative disorder (PTLD) in two (10%). There were no chronic rejection or recurrent disease. Postoperative mortality was 25%. Histologic grade by Banff schema was well correlated with clinical parameters associated with unfavorable short term prognosis. CMV infection was associated with acute cellular rejection in 6 out of 10 patients (60%). Immunohistochemical staining for CMV was more sensitive method than CMV in situ hybridization or histologic detection of viral inclusion on tissue section. It was unique that one case of PTLD developed under the circumstances of the lowest dosage of immunosuppression and took grave outcome. Based on these results, we concluded that clinicopathologic correlation with integration of all the clinical and laboratory findings is necessary in the interpretation of accurate and early diagnosis of posttransplant liver biopsies. The interrelationship between chronic rejection and CMV infection as well as pathogenetic factors of PTLD remains to be clarified through further ongoing observation.
Aspergillosis ; Autopsy ; Biopsy* ; Candidiasis ; Cytomegalovirus ; Diagnosis ; Early Diagnosis ; Humans ; Immunosuppression ; In Situ Hybridization ; Liver Transplantation ; Liver* ; Lymphoproliferative Disorders ; Mortality ; Primary Graft Dysfunction ; Prognosis ; Thrombosis ; Tissue Donors ; Transplants

The posttransplantation lymphoproliferative disorders (PTLD) are not rare complications of solid organ transplants. The incidence varies with the type of transplantation and the nature and intensity of the immunosuppressive regimens. PTLDs are unique in that they have a predilection for extranodal sites, a strong and probably causal association with Ebstein-Barr virus infection, and a poor response to the cytolytic chemotherapeutic or irradiation regimens used for treatment of malignant lymphoma. The outcomes of treatment have been disappointing, with mortality from PTLD or related complications of over 50% of patients. We experienced two cases of PTLDs in liver transplant recipients presenting with liver mass and intraabdominal lymphadenopathy. PTLDs were diagnosed by autopsy and a liver biopsy. In the case diagnosed by a liver biopsy, EBV was detected by in situ hybridization. Despite reduction of immunosuppression and conservative management, both patients died.
Autopsy ; Biopsy ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; In Situ Hybridization ; Incidence ; Liver Transplantation* ; Liver* ; Lymphatic Diseases ; Lymphoma ; Lymphoproliferative Disorders* ; Mortality ; Transplantation ; Transplants

Lymphoproliferative disorders are among the most serious and potentially fatal complications of chronic immunosuppression in organ transplant recipients. Post-transplant lymphoproliferative disorder (PTLD) is the second common malignancy occurring in patients with kidney transplantation and has a high mortality rate. The pathogenesis of PTLD in most cases appears to be related to B cell proliferation induced by infection with Epstein-Barr virus (EBV) in the setting of chronic immunosuppression. The PTLD may present a solitary tumor around the hilum of transplant kidney, but it may not by easily considered as the cause of hydronephrosis in transplant kidney because the prevalence of PTLD is low and surgical complications such as lymphocele, stricture and hematoma that obstruct the transplant ureter are much more common. Early detection is important because reduction of immunosuppressive agents may reverse progression of the disease. Furthermore, several effective treatment options were recently introduced. Here we report a case of PTLD presenting with hydronephrosis, which was completely resolved by a multimodality therapeutic approach.
Cell Proliferation ; Constriction, Pathologic ; Hematoma ; Herpesvirus 4, Human ; Humans ; Hydronephrosis* ; Immunosuppression ; Immunosuppressive Agents ; Kidney Transplantation* ; Kidney* ; Lymphocele ; Lymphoproliferative Disorders* ; Mortality ; Prevalence ; Transplants ; Ureter

BACKGROUND/AIMS: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. METHODS: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. RESULTS: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. CONCLUSIONS: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.
Age of Onset ; Arthritis, Rheumatoid ; Asian Continental Ancestry Group ; Autoimmune Diseases ; Clinical Study* ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Korea ; Lymphoma ; Lymphoma, Non-Hodgkin* ; Lymphoproliferative Disorders ; Methotrexate ; Mortality ; Retrospective Studies*

PURPOSE: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. METHODS: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. RESULTS: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. CONCLUSION: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.
Allografts ; Child ; Drug Therapy ; Epstein-Barr Virus Infections ; Female ; Fever ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; In Situ Hybridization ; Incidence ; Kidney ; Kidney Transplantation ; Liver ; Lymphoproliferative Disorders* ; Male ; Medical Records ; Mortality ; Organ Transplantation* ; Retrospective Studies ; Rituximab ; Seoul ; Tacrolimus ; Transplants* ; Viral Load

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.
Adolescent ; Age Factors ; Child ; Child, Preschool ; End Stage Liver Disease/mortality/*surgery ; Female ; Graft Rejection/epidemiology ; Graft Survival ; Herpesviridae Infections/etiology ; Humans ; Infant ; Liver Transplantation/*adverse effects/*statistics & numerical data ; Lymphoproliferative Disorders/*etiology ; Male ; Proportional Hazards Models ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Vascular Diseases/etiology

OBJECTIVETo summarize the clinical characteristics, early diagnosis, comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.

METHODData of 6 cases with PTLD seen between January 2011 and December 2013 were retrospectively analyzed. The anti-rejection drug dose adjustments, the effect of rituximab, antiviral therapy and comprehensive treatment program after surgery were explored.

RESULT(1) The diagnosis of PTLD was confirmed by histologic findings. Six cases of PTLD including 3 males and 3 females were diagnosed as congenital biliary atresia and underwent split liver transplantation. The occurrence rate of PTLD was 2.9%. (2) The median time to the development of PTLD was less than 6 months. The initial symptom of PTLD in all patients was fever and clinical manifestations of PTLD were non-specific, depending on the involving organs. Five cases of PTLD developed gastrointestinal symptoms, including diarrhea, abdominal pain, and abdominal distension. One case developed respiratory symptoms, including cough and tachypnea. Three cases had lymph node involvement. In 2 cases pathophysiology involved polymorphic lymphocyte proliferation and in 4 cases B lymphocyte proliferation. (3) Two cases died, in whom EBV DNA was not detected and were diagnosed as PTLD by surgical pathology before death. Four survived cases had high EBV-DNA load and then were diagnosed as PTLD by biopsy pathology. (4) Of the 6 cases of PTLD, 2 cases died and 4 cases survived. The overall mortality was 33%. The dead cases were only treated with laparotomy because of intestinal obstruction or perforation and the survived cases were treated with tacrolimus at reduced doses or discontinuation and rituximab. In 2 cases antiviral therapy (acyclovir) was continued, including 1 cases of intestinal obstruction treated with surgical repair. All the survived patients were followed up for 4 months to 1 year and no evidence has been found.

CONCLUSIONEBV infection is the high risk factor for PTLD after liver transplantation. Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD. Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD. A reduction in the dose of tacrolimus is suggested. Operation therapy can also play a role in the management of local complications.

Antiviral Agents ; administration & dosage ; Biliary Atresia ; therapy ; DNA, Viral ; analysis ; Drug Therapy, Combination ; Early Diagnosis ; Epstein-Barr Virus Infections ; diagnosis ; therapy ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Infant ; Liver Transplantation ; adverse effects ; Lymphoproliferative Disorders ; diagnosis ; etiology ; mortality ; therapy ; Male ; Pediatrics ; Postoperative Complications ; Retrospective Studies ; Survival Rate ; Tacrolimus ; administration & dosage