scholarly journals Development of tolerogenic strategies in the clinic

2005 ◽  
Vol 360 (1461) ◽  
pp. 1739-1746 ◽  
Author(s):  
Stuart J Knechtle
Keyword(s):  
Bone Marrow ◽  
Kidney Transplantation ◽  
Joint Venture ◽  
Organ Transplant ◽  
Juvenile Diabetes ◽  
Solid Organ ◽  
Diabetes Research ◽  
Transplant Recipients ◽  
Number Of Patients ◽  
Immunologic Assays

The study of tolerance in the clinic can be divided into three areas: (i) focused evaluation of existing tolerant transplant recipients as to their mechanism of tolerance; (ii) prospective tolerance trials, such as combined bone marrow and kidney transplantation as well as T cell depletion followed by subsequent weaning of immunosuppression; and (iii) immunologic assays to assess the likelihood of rejection or tolerance. Frankly, a very small number of patients have been transplanted with the intention of removing all immunosuppressive therapy, but several clinical trials with this aim are currently in progress, largely sponsored by the Immune Tolerance Network, a joint venture between the National Institutes of Health and the Juvenile Diabetes Research Foundation. Similarly, a reliable assay to assess tolerance has not yet been developed but a variety of approaches towards assessing rejection, and in some cases tolerance, are being developed. It would be accurate to state that many of the experimental and preclinical approaches to the induction of tolerance have resulted in better immunosuppression for human transplantation, but reliable tolerance strategies in humans have not yet been achieved. Combined bone marrow and kidney transplantation may be considered as one exception to this, but such a strategy is not generally applicable to the vast majority of solid organ transplant recipients. This review will summarize efforts to date, particularly focusing on kidney transplantation.

Impact of Pharmacy-Initiated Interventions on Influenza Vaccination Rates in Pediatric Solid Organ Transplant Recipients

2018 ◽  
Vol 8 (6) ◽  
pp. 525-530 ◽  
Author(s):  
Sara Gattis ◽  
Inci Yildirim ◽  
Andi L Shane ◽  
Staci Serluco ◽  
Courtney McCracken ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Vaccination Coverage ◽  
Influenza Infection ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Vaccination Rates ◽  
Number Of Patients ◽  
Over Time

Abstract Background In solid organ transplant (SOT) recipients, influenza infection can lead to subsequent graft dysfunction and death. Vaccination is the most effective approach to preventing influenza infection; however, vaccination rates are low, and interventions to optimize vaccine coverage are needed. The purpose of this study was to evaluate if pharmacy-initiated screening and recommendations for influenza immunization improve the rate of vaccination in pediatric SOT recipients. Methods We performed a retrospective pre-post chart review of all kidney, liver, and heart transplant recipients followed by Children’s Healthcare of Atlanta/Emory University transplant services between September 1, 2011, and February 16, 2017. Influenza vaccination coverage and influenza rates before (2011–2013) and after (2014–2016) the implementation of pharmacy-driven vaccination in SOT recipients were assessed. Results A total of 822 patients were included; 101 (13%) of these patients were diagnosed with influenza, and 40 (5%) were hospitalized secondarily during the study period. Vaccination coverage increased over time (144 [36%] patients vaccinated in 2011 vs 430 [74%] in 2016; P < .001). Influenza diagnosis rates decreased between the 2 eras (P = .006). The median time in which 50% of the population was vaccinated decreased over time from 163 days in 2012 to 94 days in 2016 (P < .001). Conclusion Within the constraints of the pre-post study design, we observed a significant increase in influenza vaccination rates after implementation of a transplant pharmacy-initiated screening and vaccination program. The number of patients diagnosed with influenza and the time to vaccination decreased after our pharmacy intervention. All efforts should be made to increase compliance with influenza vaccination; pharmacy-initiated interventions can improve protection against influenza infection in pediatric SOT recipients.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3047-3047
Author(s):  
Danielle Isadora Blumenschein ◽  
Juliana Dall Agnol da Rocha ◽  
Guilherme Fleury Perini ◽  
Iracema Esteves ◽  
Alanna Marra P. S. Bezerra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Calcineurin Inhibitor ◽  
Albert Einstein ◽  
Lymphoproliferative Disorders ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Term Survival ◽  
Post Transplant ◽  
Number Of Patients

Abstract 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. Disclosures No relevant conflicts of interest to declare.

scholarly journals 540. Prolonged Viral Shedding of SARS-CoV-2 In Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S337-S337
Author(s):  
Hannah Nam ◽  
Scott C Roberts ◽  
Sajal D Tanna ◽  
Michael G Ison
Keyword(s):  
Median Duration ◽  
Severe Disease ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Viral Kinetics ◽  
Viral Shedding ◽  
Number Of Patients

Abstract Background Solid organ transplant (SOT) recipients are more susceptible to viral infection and present with differing viral kinetics when compared to non-immunocompromised cohorts. The duration of viral shedding in SOT recipients with SARS-CoV-2 infection is unknown. Methods All SOT recipients with a diagnosed of SARS-CoV-2 by nasopharyngeal of bronchoalveolar lavage RT-qPCR from March 06, 2020 to May 31, 2020 were identified. Viral shedding duration was obtained by evaluating all subsequent SARS-CoV-2 PCR results following initial positivity over time. Severity classification was defined as mild (outpatient), moderate (hospitalized), and severe (ICU level care). Data were obtained from electronic medical record case review and analyzed with Stata 16. Results 71 patients with a positive SARS-CoV-2 PCR test were identified. 50 (70.4%) were classified as mild/moderate disease, while 21 (29.5%) had severe disease. Median age was 56.5 (IQR 45 – 61.3) years, and 56.9% (n = 41) were male. Older age was significantly associated with severe disease. A disproportionate number of patients were African American/Black or Hispanic at 72.2% (n=52). Interestingly, Caucasian race was significantly associated with less severe outcomes (p=0.038). The majority of patients were kidney transplant recipients (46, 63.9%), followed by liver (13, 18.1%), heart (6, 8.3%), lung (3, 4.2%), and pancreas (9, 12.5%) with a median duration from transplantation at 5 (IQR 3 – 17) years. Overall mortality was 5.6% (n=4), with all deaths occurring only in those with severe disease (19.1%, n=4). Prolonged viral shedding was observed in few patients, with median duration of SARS-CoV-2 PCR positivity at 32 (IQR 18.5 – 41.0) days. One kidney recipient was observed with up to 64 days of positive SARS-CoV-2 RT-PCR from initial diagnosis despite not developing severe disease. Demographics and Outcomes Duration of Viral Shedding in SOT Patients with COVID-19 Conclusion COVID-19 can lead to significant outcomes in SOT with increased mortality in those with severe disease, as well as prolonged viral shedding. Further studies are needed to elucidate the full duration of viral shedding in this population. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)

scholarly journals 918. Pilot Surveillance for Carbapenemase Gene-positive Organisms Among Hospitalized Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S493-S494
Author(s):  
June L Chan ◽  
Elizabeth Nazarian ◽  
Kimberlee A Musser ◽  
Monica Fung ◽  
Sarah B Doernberg ◽  
...  
Keyword(s):  
Klebsiella Oxytoca ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Single Individual ◽  
Transplant Recipients ◽  
Public Health Action ◽  
Organ Transplant Recipients ◽  
Number Of Patients ◽  
Carbapenemase Gene

Abstract Background Carbapenemase gene-positive organisms (CPOs) are associated with infections with high mortality rates and have the potential to facilitate epidemic spread of carbapenem resistance. Passive reporting to CDC identified CPOs among organ transplant recipients, potentially representing an emerging reservoir for spread. We aimed to determine the prevalence of CPOs in hospital units where solid organ transplant (SOT) recipients receive care in order to inform public health action to prevent transmission. Methods All healthcare facilities identified one medical unit where SOT recipients received inpatient care and conducted point prevalence surveys (PPS) of all consenting patients on 1-2 designated calendar days. We used the Cepheid Xpert® Carba-R assay to identify carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) from rectal swabs; carbapenemase-positive swabs were cultured for organisms. All laboratory testing was conducted at the Wadsworth Center, part of CDC’s Antibiotic Resistance Laboratory Network. Results Five participating hospitals performed nine PPS from September 2019 through June 2020. In total, 154 patients were screened and 92 (60%) were SOT recipients (Table). The most common transplanted organs were kidney (44, 48%) and liver (39, 42%). Carbapenemase genes were detected among 5 (5%) SOT recipients, all from a single healthcare facility; 4 (80%) were blaKPC and 1 (20%) was blaNDM. Of the positive specimens cultured, blaKPC was carried by Enterobacter cloacae complex (ECC), Klebsiella pneumoniae, and Klebsiella oxytoca and blaNDM was carried by K. oxytoca; blaKPC was carried by both ECC and K. pneumoniae in a single individual. For SOT patients with CPOs, the median interval from transplantation to swab collection was 108 days (range: 12 to 323). CPOs were only detected in 1 (2%) of 62 non-transplant patients. TABLE Characteristics of Carbapenemase Gene-positive Organism (CPO) Pilot Surveillance Participants Conclusion Among participating facilities, most did not identify CPOs among patients admitted to transplant units. These findings represent a small number of patients and facilities; additional PPS in areas with varied CPO epidemiology are needed to understand whether SOT recipients should be routinely screened for CPOs. Disclosures All Authors: No reported disclosures

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