Adapted Management of EBV Reactivation After Solid Organ Transplantation: An Effective Prevention of Post Transplantation Lymphoproliferative Disorders (PTLD). Results of the Largest Prospective Study on 251 Patients

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.

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.


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 ◽  
...  

Perfusion ◽  
2020 ◽  
pp. 026765912093936
Author(s):  
Ernest G Chan ◽  
Matthew R Morrell ◽  
Patrick G Chan ◽  
Pablo G Sanchez

The ethical concerns of refusing lifesaving treatments after receiving an already limited resource such as a solid organ transplantation in a Jehovah’s Witness patient have been discussed in the literature. Many of these studies have concluded that with a multidisciplinary approach, solid organ transplantation is possible in the setting of Jehovah’s Witness patients. To date, there are no reported cases of bilateral sequential lung transplantation in the literature. We report two successful cases of bilateral sequential lung transplantation in Jehovah’s Witness patients with excellent long-term follow-up.


2012 ◽  
Vol 56 (11) ◽  
pp. 6041-6043 ◽  
Author(s):  
Tark Kim ◽  
Heungsup Sung ◽  
Yu-Mi Lee ◽  
Hyo-Lim Hong ◽  
Sung-Han Kim ◽  
...  

ABSTRACTThere are no data on the efficacy of secondary prophylaxis againstPneumocystispneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence ofPneumocystispneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered fromPneumocystispneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence ofPneumocystispneumonia during the follow-up, regardless of secondary prophylaxis.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 816-816 ◽  
Author(s):  
Ralf Ulrich Trappe ◽  
Daan Dierickx ◽  
Heiner Zimmermann ◽  
Franck Morschhauser ◽  
Peter Mollee ◽  
...  

Abstract Background: The PTLD-1 trial has demonstrated the efficacy and safety of 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF in CD20-positive PTLD after solid organ transplantation. Median overall survival (OS) was 6.6 years, a clear improvement over the preceding rituximab monotherapy trials (2.4 years). However, response to rituximab induction predicted OS after completion of therapy. Based on the hypothesis that rituximab consolidation might be sufficient treatment for patients already in a complete response (CR) after rituximab induction, trial treatment was changed in 2007 through a protocol amendment introducing risk-stratified sequential treatment (RSST): rituximab consolidation for patients in CR after rituximab induction and R-CHOP-21 consolidation for all others. Methods: In this international, multicenter phase II trial (PTLD-1, 3rd amendment; NCT00590447), treatment-naïve adult solid organ transplant recipients diagnosed with CD20-positive PTLD were treated with rituximab (375 mg/m2 IV) on days 1, 8, 15 and 22. After restaging, patients in CR continued with four three-weekly courses of rituximab monotherapy while all others received 4 cycles of R-CHOP-21 + G-CSF. In case of disease progression during rituximab monotherapy R-CHOP was commenced immediately. The primary endpoint was treatment efficacy measured as response rates and response duration. Analysis was by intention to treat. This is the final analysis of 152 patients treated with RSST from 2007 to 2014 at centers in Germany (72), Belgium (36), France (24), Australia (7), Poland (7) and Italy (6) with a median follow-up of 4.5 years. The 70 patients treated with rituximab followed by CHOP-21 in the original PTLD-1 trial (median follow-up 5.1 years) served as a control population. Inclusion criteria and follow-up schedule were identical; there were no significant differences in the transplant- and lymphoma-related baseline factors listed below. Results: 115/152 patients were male. 69/152 were kidney, 40 liver, 18 lung, 15 heart, 5 heart/kidney, 3 kidney/pancreas and 2 heart/lung transplant recipients. Median age at diagnosis was 56 years. PTLD was late (> 1 year after transplantation) in 120/152 (79%) of patients. 67/145 (46%) PTLD were EBV-associated. 130/152 patients had monomorphic, 20 polymorphic and 2 early lesion PTLD. The overall response rate (ORR) was 111/126 (88%, CR: 88/126 [70%]). Median duration of remission (DR) was not reached; the 3-year Kaplan-Meier estimate was 82% (compared to 71% in PTLD-1). In the intention-to-treat population (152 patients), the median time to progression (TTP) was not reached either. The 3-year Kaplan-Meier estimate was 78% (69% in PTLD-1). Median OS by intention-to-treat was 6.6 years (95% CI 5.5 - 7.6) with a 3-year estimate of 70% in comparison to 61% in PTLD-1. There was no significant difference in ORR, DR, TTP or OS between EBV-positive and EBV-negative PTLD. On the other hand, response to 4 applications of rituximab was a highly significant predictor of OS, TTP and progression-free survival (PFS) despite treatment stratification (all p<0.001). 37/148 patients (25%) achieved CR with 4 cycles of rituximab and were allocated to rituximab consolidation. In this group, TTP in the intention-to-treat population was significantly longer than in the corresponding group in the PTLD-1 trial (37 patients versus 14 patients, p<0.05). In the 111 patients allocated to R-CHOP consolidation, ORR was 78/92 (85%) with 55/92 (60%) complete remissions (89% and 60%, respectively, in PTLD-1). Median TTP was not reached, the 3-year estimate was 73% (69% in PTLD-1). In patients refractory to rituximab induction, the CR rate was 22/38 (58%) with R-CHOP compared to 3/11 (27%) in PTLD-1 with CHOP (p=0.07); median PFS was 1.4 years versus 0.3 years in PTLD-1, p<0.05. The frequency of grade 3/4 leukopenia and infections was 63% and 34%, respectively. Treatment-related mortality occurred in 7%. Conclusions: This largest trial cohort in PTLD to date demonstrates for the first time that treatment stratification by response to rituximab induction is feasible, safe and effective. Rituximab consolidation in early rituximab responders results in significantly better disease control compared to CHOP consolidation. The addition of rituximab to CHOP chemotherapy improves outcome in patients refractory to rituximab monotherapy. Disclosures Trappe: Mundipharma: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau. Zimmermann:Roche: Honoraria; Celgene: Other: Travel support. Morschhauser:Genentech Inc./Roche: Other: Advisory boards. Mollee:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zaucha:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau. Dührsen:Roche: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Hüttmann:Amgen: Research Funding; Roche: Research Funding. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau. Kliem:Astellas: Honoraria; Fresenius: Honoraria; Genzyme: Honoraria; Novartis: Honoraria; Roche: Honoraria; Raptor: Honoraria. Leblond:Janssen: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau. Choquet:Janssen: Consultancy; Roche: Consultancy.


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