Non-HLA Antibodies Post-Transplantation: Clinical Relevance and Treatment in Solid Organ Transplantation

Author(s):  
Duska Dragun ◽  
Björn Hegner
BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.


2007 ◽  
Vol 86 (8) ◽  
pp. 599-607 ◽  
Author(s):  
Sylvain Choquet ◽  
Stephan Oertel ◽  
Veronique LeBlond ◽  
Hanno Riess ◽  
Nathalie Varoqueaux ◽  
...  

2007 ◽  
Vol 25 (31) ◽  
pp. 4902-4908 ◽  
Author(s):  
Britta Maecker ◽  
Thomas Jack ◽  
Martin Zimmermann ◽  
Hashim Abdul-Khaliq ◽  
Martin Burdelski ◽  
...  

Purpose To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. Patients and Methods A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. Results PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). Conclusion Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.


2016 ◽  
Vol 3 (4) ◽  
pp. 4
Author(s):  
Mina Al-Badri ◽  
Kunam Reddy ◽  
Paru David ◽  
Raymond Heilman ◽  
Christine Snozek ◽  
...  

A 21-year-old female with end stage renal disease underwent a non-related renal transplantation from a deceased pregnant donor. The recipient had a negative serum pregnancy test prior to her surgery. However postoperatively, a rise in her serum human chorionic gonadotrophin (hCG) level, which lasted several days, was documented. Solid organ transplantation is known to transmit various infections, malignant cells and antibodies from donor to recipient but no previous reports described transmission of hCG. This case report highlights the importance of considering this possibility when managing post-transplantation hormonal disturbances. Further research is warranted to evaluate the different mechanisms through which transmission occurs between donor and recipient.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2932-2932
Author(s):  
Sylvain Choquet ◽  
Shaida Varnous ◽  
Claire Deback ◽  
Corinne Amiel ◽  
Jean Louis Golmar ◽  
...  

Abstract Background: Post-transplantation lymphoproliferative diseases (PTLD) represent a rare but aggressive graft complication. Patients who have received a solid organ transplantation have a 20 to 120 fold higher incidence of non-Hodgkin’s lymphoma. EBV reactivation represents a major predictive factor for PTLD, especially during the first year after transplantation, but there is no consensual attitude in this situation Aim: We conducted a monocentric prospective study in the Hospital of Pitie Salpêtriere, Paris, France, on all new heart or lung-heart transplanted patients. EBV viral load was systematically followed and confirmed reactivations were treated or surveyed, depending on viral load. Methods: 101 patients were included between January 2004 and December 2006. Twelve to 15 blood samples per year were analysed. If the viral load was more than 50N, patients were treated by diminution of the immunosupression and one injection of rituximab (375 mg/m2), between 10N and 50N, only the immunosupression was modified, and rituximab was used in case of failure, and below 10N, a simple survey was decided. Correlation with CMV reactivation has been analysed. Results: 45 (44%) patients presented an EBV reactivation. A simple survey has been sufficient in 29 cases, immunosupression decrease was the only treatment in 8 cases, 2 patients had to be treated in a second step by rituximab, because of stability or increase of the viral load beside the immnosupression modification, and 6 patients have been treated by rituximab as first treatment. All EBV reactivations have been controlled by this attitude, no PTLD has been diagnosed during this period and graft rejection rate did not change. From 1987 to December 2003, 24 PTLD have been treated in the same unit (18 EBV positive, 1 unknown), of which 13 were early PTLD (all EBV positive) with a diagnosis of less than one year after transplantation. We did not find any correlation between EBV and CMV reactivations. Conclusion: EBV reactivation after organ transplantation can be managed by diminution of immunosupression and/or rituximab, depending on viral load, without serious complication. A prolongation of this study and a longer follow-up are necessary to know if this attitude decreases the incidence of early EBV positive PTLD.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 592-592
Author(s):  
Sylvain Choquet ◽  
Shaida Varnous ◽  
Claire Deback ◽  
Alain Pavie ◽  
Véronique Leblond

Abstract Abstract 592 Background: PTLD represent a rare but aggressive graft complication. Patients who have received a solid organ transplantation have a 20 to 120 fold higher incidence of non-Hodgkin's lymphoma. EBV reactivation represents a major predictive factor for PTLD, especially during the first year after transplantation, but there is no consensual attitude in this situation Aim: We conducted a monocentric prospective study in the Hospital of Pitie Salpêtriere, Paris, France, on all new heart transplanted patients. EBV viral load (EVL) on whole blood samples was systematically followed and confirmed reactivations were treated depending on viral load. Methods: All heart transplanted patients who had at least one EVL between January 2004 and December 2008 were included. Immunosuppression consisted on anti-lymphocyte sera, ciclosporin, mycophenolate-mofetyl (MM) and prednisone. Twelve to 15 blood samples per year were analysed. If the EVL was more than 105 copies/ml, a CT scan or a PET-san was performed in order to detect any PTLD and patients were treated by diminution of the immunosupression (DIS), mainly by MM arrest. One injection of Rituximab (R) (375 mg/m2) was used in case of failure and/or if EVL was over 106 copies/ml. Results: A total of 251 patients were included, 59 femals/192 men, of a median age of 50 years [16-72]. All but 6 were EBV positive before the graft. Reactivations were detected in 29 cases (11,55%) and treated by DIS only in 20 cases, DIS followed by R in 5 and directly by DIS and R in 4. All EBV negative patients developed a primoinfection in the first year, 2 with an EVL over 105, one presented non documented hepatic lesions which disappeared after DIS. All EBV reactivations were controlled, with a relapse in only one case (reactivations treated the first time by DIS, 10 months later by DIS and R and 6 months later by DIS). With a median follow-up of 1118 days [53-2100] only one PTLD has been diagnosed (in a patient lost to follow up and taken in charge in an other unit) and 24 patients died (9,5%). Analyse of DIS +/− R on graft rejection and potential link between CMV reactivation and EBV reactivation will be presented at the ASH. From 1987 to December 2003, 24 (1,8/year) PTLD have been treated in the same unit (18 EBV positive, 5 negative, 1 unknown), of which 13 were early PTLD (all EBV positive) diagnosed within one year post transplantation. Conclusions: EBV reactivation after organ transplantation can be managed by diminution of immunosupression and/or rituximab, depending on viral load, without serious complication. This adapted management seems to decrease dramatically the incidence of EBV positive PTLD. Disclosures: Choquet: ROCHE: Consultancy. Leblond:ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.


2018 ◽  
Vol 14 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Philip J. Bierman

There is an increasing number of long-term survivors of Hodgkin and non-Hodgkin lymphoma. These people may have a need for subsequent solid organ transplantation, often as a result of late effects of their lymphoma treatment. There is abundant literature demonstrating that patients with a history of lymphoma are appropriate candidates for solid organ transplantation. Long-term survival without relapse and with a functioning graft is possible. Patients with a history of post-transplantation lymphoproliferative disorders and patients who have received a prior hematopoietic stem-cell transplantation may also be candidates. Although high-level supporting evidence is not available, most guidelines recommend a waiting period of 2 to 5 years after lymphoma treatment before patients undergo solid organ transplantation. Each patient with a history of lymphoma requires a multidisciplinary approach and should be evaluated on a case-by-case basis before consideration of solid organ transplantation.


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