Post-transplant Lymphoproliferative Disorder In Recipients Research Articles

Post-transplant Lymphoproliferative Disorder in Recipient’s Reconstructed Middle Hepatic Vein After Pediatric Living Donor Liver Transplant: A Case Report

BackgroundPost-transplant lymphoproliferative disorder (PTLD) is known as one of the most frequent post-transplant neoplastic diseases, which may lead to recipient and graft morbidity after liver transplant. PatientA 14-year-old boy received pediatric living donor liver transplant (right living graft) 29 months ago, with etiology of biliary atresia. During 22-month follow-up after transplant, computed tomography and positron emission tomography with computed tomography scan showed a single progressive mass locating in the graft cutting surface with occlusive reconstructed middle hepatic vein (MHV). Serology was negative for Epstein-Barr virus serology. Mild fever and pneumonia did not improve after 1-week intravenous antibiotics. PTLD was considered. ResultsA surgical resection was scheduled and performed in compliance with the Helsinki Congress and the Istanbul Declaration. During laparotomy, a single mass located in the reconstructed MHV from segment V to the inferior vena cava was confirmed. Postoperative immunohistochemical result showed CD 3(+), CD 20(+), CD 38(+), CD 10(−), CD 56(−), Ki-67(+, 20%-30%), Epstein-Barr virus–encoded RNA(−), and Epstein-Barr virus nuclear antigen 2(−). Polymorphic PTLD was eventually diagnosed. No recurrence or new set lesions were detected after 6-month follow-up. ConclusionsThis is the first case describing PTLD may originate from reconstructed MHV after pediatric living donor liver transplant. As a life-threatening complication of liver transplant, surgical resection should be considered as a safe and feasible treatment for the single resectable mass.

Post-Transplant Lymphoproliferative Disorders in Transplant Recipients: 14-Yr Experience at the Hospital Israelita Albert Einstein - Brazil

Introduction: The number of patients who have undergone organ and bone marrow transplantation continues to increase, as does long-term survival. Post-transplant lymphoproliferative disorders (PTLD) are potentially life-threatening complications after solid organ transplantation. Epstein-Barr virus (EBV) infection that leads to uncontrolled B cell proliferation and tumor formation. PTLD is relatively common malignancy after transplantation and is seen up to 10% of all solid organ transplant recipients, and varies considerably among the different types of organs transplanted. We sought to determine incidence and mortality risk of PTLD in recipients of Hospital Israelita Albert Einstein, Sao Paulo, Brazil.Patient and Methods: We conducted a retrospective observational study of 3006 recipients of lung, kidney, liver, pancreas, heart and bone marrow between 2002 and 2015. A total of 26 cases (0.8%) of PTLD were identified in 3006 transplants. Kaplan-Meier analysis was performed for PTLD patient survival after PTLD.Results: Median interval from transplantation to diagnosis was 49 (4-150) months. Median age was 49 years (12-73) and 73% were men. Histological subgroups included: Monomorphic PTLD (50%), Hodgkin Lymphoma (11,5%), Burkitt (15,3%), Anaplastyc large cell (7,6%) and Plasmacytic Hyperplasia (15,3%). Sixteen patients (61,5%) were EBV (+) and eleven (42,3%) were IPI III-IV only two had bone marrow infiltration. Treatment of PTLD varied according to stage and clinical circumstances: six patients (23%) were treated with Rituximab only and seventeen (65,3%) treated with R-chemotherapy. Nine (34,6%) patients died. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival, since 5 patients remain alive. The median overall survival was 1260 days, and 2-years overall survival was 65,4%.Conclusion: PTLD after solid organs transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome. We found a paucity of early onset PTLD in our cohort with only one case in the first posttransplant year. Potential contributing factors included a high prevalence of previous EBV virus exposure. The rate of PTLD malignancies in our group is comparable to that reported in other centers in Europe and North American, since it is the largest series reported by a single institution in South America. Consistent with the known antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival. DisclosuresNo relevant conflicts of interest to declare.

HLA Polymorphisms and Epstein-Barr Virus Infection In The Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundEpstein-Barr virus (EBV) infection/reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cause fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. The development of EBV infection/reactivation and EBV-associated diseases are closely related to the immune function. Human leukocyte antigen (HLA) molecules are responsible for antigen processing and presentation to the immune system. Thus, it is supposed that HLA polymorphisms might be associated with EBV infection/reactivation and EBV-associated diseases. In this study, HLA polymorphisms and EBV infection/reactivation or EBV-associated diseases in the recipients of allo-HSCT were analyzed. MethodsThree hundred and forty-nine recipients undergoing allo-HSCT were enrolled in this study between July 2008 to June 2013. For recipients and their donors, HLA-A, -B and HLA-DR were analyzed using PCR-sequence specific oligonueleotide probing (PCR-SSOP). The EBV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR). ResultsWith a median follow-up of 389 days post-transplantation (range, 7 to 1828 days), 96 cases developed EBV infection/reactivation and 40 developed EBV-associated diseases including 27 EBV-PTLD and 13 other EBV-associated diseases (i.e. 7 fever, 1 pneumonia, 2 encephalitis, 1 hepatitis, 1 encephalitis accompanying pneumonia and 1 enteritis accompanying hepatitis). The 3-year cumulative incidence of EBV infection/reactivation and EBV-associated diseases were 29.1%±2.6% and 13.1%±2.0%, respectively. 43.8% of the recipients with HLA-A11 developed EBV infection/reactivation, compared with 56.5% of those without HLA-A11 (p=0.039). Multivariate analysis showed that HLA-A11 was a protective factor for EBV infection/reactivation (OR 0.497, 95% confidence interval [CI] 0.284-0.869, p=0.014). The recipients who had the donors with HLA-A31 had a higher incidence of EBV-associated diseases than those whose donors did not have HLA-A31 (10.3% vs. 2.9%, p=0.046); more patients carried HLA-B44 suffered EBV-associated diseases than those not carried HLA-B44 (7.7% vs. 1.3%, p=0.035). In multivariate analysis, recipient HLA-B44 were confirmed to be a risk factor for EBV-associated diseases (OR 17.749, 95% confidence interval [CI] 1.946-161.917, p=0.011). The incidence of PTLD in the recipients with HLA-A74 was 7.4%, compared with 0.6% in those without HLA-A74 (p=0.031); the incidences of PTLD in recipients whose donors had and did not have HLA-DR04 were 37.0% and 20.2%, respectively (p=0.042). Multivariate analysis showed that recipient HLA-A74 (OR 11.350, 95%CI: 1.119-115.178, p=0.040) and donor HLA-DR04 (OR 3.227, 95%CI: 1.323-7.873, p=0.010) were risk factors for development of PTLD. ConclusionOur data suggest that HLA polymorphisms might affect EBV infection/reactivation and EBV-associated diseases. Disclosures:Liu:This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Three cases of posttransplant lymphoproliferative disorder in recipients of liver transplantation

Three cases of posttransplant lymphoproliferative disorder in recipients of liver transplantation

Postransplant lymphoproliferative disorder localized near the allograft in renal transplantation.

Posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, develops in approximately 1% of renal allograft recipients. Typically, PTLD is a proliferation of B-cells associated with Epstein-Barr virus (EBV) infection; it is said to be most often a systemic disease. Involvement occasionally is localized near the allograft. This is a retrospective analysis of all cases of PTLD in recipients of 1474 renal transplants performed at University of Alabama at Birmingham between 1993 and 1997. Of 14 patients developing PTLD, 10 had disease localized near the allograft. The mean interval from transplantation to diagnosis was 221 +/- 70 days. All patients presented with renal dysfunction; an ultrasound examination revealed a hilar mass, with hydronephrosis in five and stenosis of renal vessels in eight. No patient had lymphadenopathy, according to computerized tomographic or magnetic resonance imaging findings. After reduction of immunosuppressive therapy, seven required a nephrectomy because of rejection, progressive dysfunction, or mass enlargement. Tissue recovered in four patients was consistent with PTLD; the tumors in the remaining three patients were unresectable and regressed. One patient died 1 month after a nephrectomy, and another died 4 years after surgery; neither had evidence of PTLD when they died. Three patients retain functional grafts without clinical or radiographical evidence of progression. All patients with disseminated disease died. In a large cohort of renal allograft recipients, PTLD affected 1%. Disease localized near the allograft was the most common variant. For most patients with localized disease, the outcome was graft loss, and the mortality was low. Localized PTLD should be considered in the differential diagnosis of allograft dysfunction in the 1st posttransplant year.

Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants.

Posttransplant lymphoproliferative disorder (PTLD) has been treated with decreased immunosuppression, antiviral medications, anti-B lymphocyte agents, radiation therapy, and/or chemotherapy. However, a standardized stepwise approach to treatment has not been previously evaluated. In the present study, 19 consecutive patients presenting to a single institution with newly diagnosed PTLD were treated according to a sequential protocol that consisted of (1) a reduction in immunosuppressive medications plus, if feasible, resection or definitive radiation therapy of localized disease, (2) interferon-alpha, and (3) systemic chemotherapy. Of the 3 patients presenting exclusively with localized disease, two were treated with resection of pulmonary parenchymal nodules and one was treated with radiation therapy to a paraspinous mass, without evidence of recurrence at a mean follow-up of 31 months (range, 8 to 46 months). Sixteen patients presented with PTLD not amenable to local therapy, and they were treated daily with 3x10(6) units/m2 subcutaneous interferon-alpha. Total regression of PTLD (defined as disappearance of the tumor mass by physical examination or computed tomography scanning) was found in 8 of 14 patients who received at least 3 weeks of interferon therapy. Interferon-alpha therapy was continued for 6 to 9 months in the eight patients judged to be responders. None of these patients have relapsed to date with the same neoplastic clone. Two patients, however, developed new neoplastic clones. Seven patients received systemic chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n=1), EPOCH (etoposide, vincristine, and doxorubicin administered as a continuous infusion, with an intravenous bolus of cyclophosphamide and oral prednisone) (n=4), or EPOCH followed by DHAP (dexamethasone, cytarabine, and cisplatin) (n=2) after failure of interferon-alpha; five patients had a complete response. Only 1 of the 19 patients died of uncontrolled PTLD. These results suggest that the majority of solid organ transplant recipients who develop PTLD can be safely and successfully treated using a sequential approach to therapy.