Characteristics and Outcomes Following Pulmonary Cryptococcosis in Solid Organ Transplantation: Comparison With Nonsolid Organ Transplant Patients

CHEST Journal ◽  
2013 ◽  
Vol 144 (4) ◽  
pp. 1020A
Author(s):  
Angel Brown ◽  
Keith Wille ◽  
John Baddley ◽  
Peter Pappas
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Pulmonary Cryptococcosis ◽  
Transplant Patients

scholarly journals Strategy to achieve biomarker-driven immunosuppression after solid organ transplantation by an academic-industry partnership within the European BIO-DrIM consortium

2016 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Hans-Dieter Volk ◽  
Bernhard Banas ◽  
Frederike Bemelman ◽  
Oriol Bestard ◽  
Sophie Brouard ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Transplant Patients ◽  
End Stage

Solid organ transplantation has emerged as the “gold standard” therapy for end-stage organ failure as it improves both quality of life and survival. Despite the progress in short-term graft survival, that is closely associated with the impressive reduction of acute rejections within the first year, long-term graft and patient survival remain almost un-changed and unsatisfactory. Incomplete control of chronic allograft injury but particularly the adverse effects of long-term immunosuppression, such as graft toxicity, diabetes, cardiovascular events, infections, and tumours continue to challenge the long-term success. In general, immunosuppression is applied as one-size-fits-all strategy. This can result in over- and under-immunosuppression of patients with low and high alloresponsiveness, respectively. Trial- and -error strategies to minimize or even completely wean of immunosuppression have a high failure rate. Consequently, there is an unmet medical need to develop biomarkers allowing objective risk stratification of transplant patients. To achieve this goal, we engaged in an academic-industrial partnership. The central focus of the European-wide BIO-DrIM consortium (BIOmarker-Driven IMmmunosuppression) is the implementation of biomarker-guided strategies for personalizing immunosuppression to improve the long-term outcome and to decrease the adverse effects and costs of chronic immunosuppression in solid organ transplant patients. The concept includes four innovative investigator-driven clinical trials designed by the consortium.

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Future Directions ◽  
Prevention And Treatment ◽  
Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

scholarly journals Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins
Keyword(s):  
Organ Transplantation ◽  
Record Linkage ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Study Cohort ◽  
Solid Organ ◽  
Post Transplantation ◽  
Increased Risk ◽  
Risk Of Cancer

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.

Neurocognitive Effects of Solid Organ Transplantation

2010 ◽  
Author(s):  
Nataliya Zelikovsky ◽  
Debra S. Lefkowitz
Keyword(s):  
Organ Transplantation ◽  
Survival Rates ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Chronic Illnesses ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Neurocognitive Outcomes ◽  
Medical Advances

The first successful organ transplant was a kidney transplant performed between identical twins in 1954. Since that time, major medical advances have been made to help improve survival rates for transplant recipients. In 2008, there were 1,964 solid organ transplants performed for children under age 18 (2007 Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients [OPTN/SRTR] Annual Report 1997–2006). Currently, approximately 1,830 pediatric patients are awaiting some type of solid organ transplant (2007 OPTN/SRTR Annual Report 1997–2006). Organ transplantation in children is relatively recent compared to other treatments for children with chronic illnesses. The focus over the first few decades has been on medical advances and improving survival rates for transplant patients. In the recent years, increasing attention has been given to the developmental, neurocognitive, and psychosocial outcomes prior to transplant and in the short-term period post transplant. Most chronic illnesses and acute traumatic medical events have implications for neurocognitive outcomes. End-stage disease of the liver, kidney, heart, and lung are all believed to affect intellectual, academic, and neurocognitive functions. Gross neurodevelopmental deficits have become less common due to early medical intervention (e.g., improved nutrition, surgical intervention, reduced exposure to aluminum (Warady 2002). Organ transplantation is believed to ameliorate the deleterious long-term developmental and neurocognitive effects, but this topic has received little attention in the literature, and the available results with regard to intellectual, academic, and neurodevelopmental results have been mixed. In a combined sample of solid organ transplant patients, 40% had clinically significant cognitive delays (Brosig et al. 2006). Examining the impact of different underlying disease processes and transplantation of each solid organ separately is critical. Thus, we discuss the neurocognitive outcomes of each organ group separately in this chapter. Neurocognitive outcomes can be assessed in a variety of ways depending upon the age of the child. Among infants and toddlers, neurocognitive functioning is measured by an assessment of motor function, social and environmental interaction, and language development. Assessment of older children may involve the evaluation of intelligence, academic achievement, emotional and behavioral functioning, and adaptive skills.

scholarly journals A Single-Center Retrospective Study of 140 Patients with Post-Transplant Lymphoproliferative Disorder Following Solid Organ Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4227-4227
Author(s):  
Michael D Jain ◽  
Ryan Lam ◽  
Rashmi S Goswami ◽  
Krystyna Tybinkowski ◽  
Parneet K Cheema ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Competing Risks ◽  
Research Funding ◽  
Lymphoproliferative Disorder ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Early Relapse ◽  
Transplant Program ◽  
Poor Outcomes

Abstract Background: Post-transplant lymphoproliferative disorder (PTLD) is an uncommon, heterogeneous disease that occurs in the setting of immune suppression following solid organ transplantation. As the transplant population ages over time, the spectrum of PTLD histologies and their treatment has evolved; we report here our recent experience with PTLD from a large multi-organ transplant program. Methods: We identified patients from the Multi-Organ Transplant Program at University Health Network (UHN) who were diagnosed with PTLD between January 1, 2000 and December 31, 2015. We describe the characteristics and outcomes of this cohort, with a focus on the outcome of patients with the diffuse large B cell (DLBCL) subtype of PTLD treated in the rituximab era. Results: A total of 140 patients were diagnosed with PTLD at UHN during this time period (Table 1): 38% were female and median age at time of diagnosis was 50 (interquartile range, IQR Q1/Q3, 37 to 62 years). The most commonly implicated transplants were liver and kidney (33% and 32%), as well as lung (20%) and heart (7%). The median time from organ transplantation to PTLD diagnosis was 61 months (IQR 9 to 136), with 70% of cases occurring more than 12 months following solid organ transplant. Pathologically, the majority of the patients had monomorphic PTLD, with DLBCL (n = 86) being most common. Where classifiable by the Hans algorithm (n = 68), the majority of the DLBCL types were of the non-germinal center B cell type (non-GCB, 76.5%). Of 24 DLBCL patients with available FISH, 7 had a MYC translocation (29%). Treatment and outcome varied by PTLD subtype (Table 2). For the overall cohort (n = 140), the median OS was 5.1 years. Highlighting competing risks, less than half of patients died of PTLD, with the remainder of mortality due to complications of solid organ transplantation, or less commonly, due to treatment-related mortality. Polymorphic PTLD (n = 17) was treated in a variety of ways ranging from reduction in immunosuppression (RIS) alone to R-CHOP; median OS was 10.3 years. Less common histologic subtypes (Hodgkin, Burkitt, T cell) were treated with therapies specific to those lymphomas. For DLBCL (n = 86), treatment consisted of RIS alone (10.5%; OS 4.4 years) or RIS followed by local treatment (involved field radiation or surgical resection) (7.0%; OS not reached); single agent rituximab (R) (22.1%; OS not reached); sequential R followed by CHOP (11.6%; OS 1.5 years), or upfront R-CHOP (43.0%; OS 3.4 years). Median OS for patients classified as non-GCB was not worse than those classified as GCB (OS 6.2 vs. 4.7 years, p = 0.93). In the DLBCL cohort, 20 patients had progression during or after first line therapy, with 14 patients receiving additional treatment. Patients with early relapse during initial therapy or within the first 3 months (n = 13) did poorly compared to patients with later relapse occurring after 3 months (n = 7; median OS 0.7 vs 5.6 years, p < 0.01). This was similar to the entire cohort, where 40 patients relapsed and early relapsed/refractory patients also had poor outcomes compared to late relapsing patients (median OS 0.8 vs. 5.1 years, p <0.01). Six patients in the overall cohort had an autologous stem cell transplant for progressive disease; 4 remain in remission after 5 years (range, 1.3 to 5.8 years follow-up). Conclusion: In this recent retrospective cohort, PTLD was generally late onset and the median OS of all patients was 5 years. The most common histology was DLBCL (non-GCB subtype), but cell of origin did not influence outcome. Patients with early relapse or refractory disease had poor overall survival. Due to competing risks and comorbidities, many PTLD patients continue to have poor outcomes despite modern treatment strategies. Disclosures Jain: Roche Canada: Research Funding. Prica:Janssen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria. Kuruvilla:Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Honoraria; Roche Canada: Consultancy, Honoraria, Research Funding; Merck: Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria.

scholarly journals Incidence and Risk Factors Associated with Fatal Graft Vs Host Disease after Solid Organ Transplantation in United Network of Organ Transplant Database

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4067-4067
Author(s):  
Pavan Tenneti ◽  
Jiaxian He ◽  
Peter Lalli ◽  
Pranav Tenneti ◽  
Michael R. Grunwald ◽  
...  
Keyword(s):  
Risk Factors ◽  
Organ Transplantation ◽  
Cause Of Death ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ ◽  
Cell Transplant ◽  
Abo Incompatibility ◽  
And Gender ◽  
High Level

Abstract INTRODUCTION Graft vs host disease (GVHD) is a rare complication after solid organ transplantation ( ̴ 1-2% with liver and ̴ 5.6% with intestines), but is associated with high mortality (70-80%). In contrast to GVHD following hemopoietic stem cell transplant, bone marrow infiltration by donor T lymphocytes leading to cytopenia ( ̴ 80%) is a common manifestation of GVHD after solid organ transplantation (Murali et. al., 100(12), Transplantation, January 2016). The risk factors associated with GVHD occurring after solid organ transplantation have not been well characterized, but single institution studies have suggested donor/recipient (D/R) HLA mismatch, ABO incompatibility and gender mismatch playing important roles. However, some studies have identified that similarities in HLA type which permit mismatches unrecognized by the recipient as a common mechanism preventing rejection of donor lymphocytes, which then can cause GVHD in the recipient. In order to evaluate potential risk factors, we reviewed the transplant data of patients in whom GVHD was listed as the cause of death from United Network of Organ transplant database (UNOS), the database that contains all US organ transplant data. METHODS From the UNOS database we obtained information of patients that underwent liver or intestinal transplantation between 1987-2020 in the US. The patients for whom GVHD was reported as the cause of death were identified. Baseline D/R and transplant variables were collected. Patient or transplant related characteristics were presented via descriptive statistics. Corresponding P-values were determined using Chi-square test for categorical variables and two-sample t-test for continuous variables. The incidence of mortality caused by GVHD was estimated using the cumulative incidence method, accounting for non-GVHD related death as a competing risk. All statistical tests were two sided, and a P-value &lt; 0.05 was considered significant. RESULTS Of a total of 179,355 patients that underwent liver transplantation, 216 (0.1%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 86,434 patients (48.2%). HLA mismatch was grouped into low level (0-3) and high level (4-6). Low level HLA mismatch was 24.6% in the GVHD group compared to 16.2% in patients that are alive or died of non-GVHD related causes (non-GVHD group). High level mismatch was 75.4% in GVHD group and 83.8% in the non-GVHD group (P=0.013). Other risk factors including gender mismatch (40.3% vs 42.5%, P=0.536), ABO incompatibility between D/R (0.5% vs 1.4%, P=0.42) and use of live donors (1.9% vs 4.3%, p= 0.09) were similar between the two groups. Patients in the GVHD group were older with median age of recipient being 59 years compared to 53 years in the non-GVHD (P&lt;0.001). Graft failure was more common in the GVHD group compared to non-GVHD group (33.8% vs 17.1%, P&lt;0.001). Of a total of 3,153 patients that underwent intestinal transplantation, 20 (0.6%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 2859 patients (90.6%).The high-level HLA mismatch (83.3% vs 84.7%, P=0.749), gender mismatch (40% vs 47.1%, P=0.655) and ABO incompatibility (0% vs 0.2%, P=0.757) between D/R were similar between the GVHD group and non-GVHD group among intestinal transplant patients. Conclusions In patients that undergo hematopoietic stem cell transplant, HLA and gender mismatch between D/R have been recognized as risk factors for GVHD. Based on the largest analysis of solid organ transplant database, traditionally considered GVHD risk factors like HLA and gender mismatch between D/R do not appear to be significantly associated with severe GVHD leading to death. Recipient age and graft failure are significantly associated with GVHD related deaths in liver transplant patients. These findings suggest that other risk factors for severe GVHD leading to death after solid organ transplant than those previously reported in single institution studies should be examined and underscore the need for additional studies. Figure 1 Figure 1. Disclosures Grunwald: Med Learning Group: Other; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; PRIME: Other; PER: Other; Karius: Consultancy; Sierra Oncology: Consultancy; Blueprint Medicines: Consultancy; Incyte: Consultancy, Research Funding; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; Stemline: Consultancy; Gilead: Consultancy; Cardinal Health: Consultancy; Trovagene: Consultancy; MDEdge: Other. Copelan: Amgen: Consultancy.

scholarly journals Choice of Study Populations for Vaccines

2020 ◽  
Vol 221 (Supplement_1) ◽  
pp. S128-S134
Author(s):  
Paul Griffiths ◽  
Brenna Hughes
Keyword(s):  
Natural History ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Clinical Trial Design ◽  
Active Immunization ◽  
Solid Organ ◽  
Cell Transplant ◽  
Natural Immunity ◽  
Childbearing Age ◽  
Transplant Patients

Abstract The natural history of cytomegalovirus (CMV) infection is complex. Individuals may experience primary infection, reactivation of latent infection, or reinfection with a new strain despite natural immunity. The ability of this virus to continue to replicate despite substantial immune responses is attributable to the many immune evasion genes encoded within its genome. Given this complex natural history and immunology, the design of clinical trials of CMV vaccines may require components not usually found in trials of vaccines designed to protect against viruses that cause only acute infections. In this article, we focus on specific aspects of clinical trial design that could be adopted to address the complexities of CMV infections. We consider women of childbearing age, toddlers, recipients of solid organ transplantation, and stem cell transplant patients, emphasizing the parallels between women and solid organ transplantation that could allow vaccines to be developed in parallel in both these patient groups. We emphasize the potential for studies of passive immunity to inform the selection of immunogens as candidates for active immunization and vice versa. We also illustrate how application of whole-genomic sequencing could document whether vaccines protect against reactivation or reinfection of CMV or both.

scholarly journals A case of positive pregnancy test in a sexually inactive solid organ transplant recipient -- can human chorionic gonadotropin be transmitted through solid organ transplantation?

2016 ◽  
Vol 3 (4) ◽  
pp. 4
Author(s):  
Mina Al-Badri ◽  
Kunam Reddy ◽  
Paru David ◽  
Raymond Heilman ◽  
Christine Snozek ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Organ Transplant Recipient ◽  
Solid Organ Transplant Recipient ◽  
Solid Organ ◽  
Post Transplantation ◽  
Pregnancy Test ◽  
Stage Renal Disease ◽  
End Stage

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.

scholarly journals Immunomodulatory Therapies for COVID-19 in Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (4) ◽  
pp. 379-389 ◽  
Author(s):  
Mario Fernández-Ruiz ◽  
José María Aguado
Keyword(s):  
Case Reports ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Case Series ◽  
Control Group ◽  
Supporting Evidence ◽  
Solid Organ ◽  
Transplant Patients ◽  
Group Limit ◽  
Immunomodulatory Therapies

Abstract Purpose of Review Severe coronavirus disease 2019 (COVID-19) is characterized by the development of a deleterious hyperinflammatory response, in which the pleiotropic cytokine interleukin (IL)-6 plays a pivotal role. The administration of immunomodulatory therapies has been proposed to revert the tissue damage induced by COVID-19-related cytokine release syndrome (CRS). The present review summarizes the biological rationale and available clinical experience with this therapeutic strategy in the specific scenario solid organ transplantation (SOT). Recent Findings A number of case reports, case series, and non-controlled cohort studies have assessed the efficacy and safety of the anti-IL-6-receptor monoclonal tocilizumab in SOT (namely kidney transplantation) recipients with COVID-19 pneumonia and CRS. Although the heterogeneity in patient management and the lack of a control group limit the interpretation of these results, tocilizumab therapy appears to provide some clinical benefit in post-transplant COVID-19 and to be reasonably safe in terms of bacterial superinfection. A large randomized clinical trial (RCT) has shown survival benefit with adjuvant corticosteroids in non-transplant patients, but supporting evidence is scarce for SOT recipients and confounded by the variable adjustment of baseline immunosuppression. Anecdotal experiences have been reported with the use of the anti-IL-1 agent anakinra and the NLRP3 inflammasome inhibitor colchicine in this population. Summary Immunomodulation has emerged as a promising option for SOT recipients with COVID-19-related CRS, with available experience mainly restricted to the anti-IL-6 agent tocilizumab. However, the supporting evidence is scarce and of low quality. In the absence of RCT, observational studies including well-matched control groups should be designed in future.

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