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Introduction: Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal insufficiency. Death in early infancy is due to liver failure. Patients and methods: We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect. Results: He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism. Conclusion: The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics
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Background: Allogeneic hematopoietic cell transplantation (HCT) with ex vivo T cell receptor (TCR) alphabeta+ T cell and CD19+ B cell depletion is an effective approach for children with primary immune deficiency disorders (PIDD) as it combines advantages of high CD34+ cell dose facilitating rapid engraftment with low risk of Graft Versus Host Disease (GVHD). The ideal pre-conditioning regimen that facilitates robust donor engraftment without increasing risk of transplant related mortality has not been well defined with this approach. Method(s): We report the outcomes of 4 pediatric subjects: Chronic Granulomatous Disease (CGD) (2), Wiskott Aldrich Syndrome (WAS) (1), and RAC2 deficient Severe Combined Immunodeficiency (1) who underwent haploidentical HCT with TCRalphabeta+ T cell/CD19+ depletion at Johns Hopkins All Children's Hospital/Moffitt Cancer Center from 2020-2022 (NCT04414046). Pre-conditioning regimen consisted of distal thymoglobulin (7.5 mg/kg), fludarabine (175 mg/m2), thiotepa (10 mg/kg) and pharmacokinetic guided busulfan targeting a cumulative area under curve (cAUC) (65-75 mgxhr/L). Rituximab (200 mg/m2) was administered on day +1. Result(s): The median age at HCT was 51 months (range 10-163 months). All patients received mobilized peripheral blood stem cells from HLA- haploidentical donors (paternal=1, maternal=1 sibling=2). Median busulfan cAUC for all patients was 69 mgxhr/L (range 65-76). Median CD34 and TCR alphabeta T cell dose was 9.13x106 cells/kg (range 7.0-18.9x106) and 0.7x105 cells/kg (range 0.09-1.0x105). Median times to neutrophil and platelet engraftment were 11 days (9-12) and 11 days (range 8-15), respectively. All 4 patients are alive with median follow-up of 19.5 months (range 7-24). One patient developed late VOD without organ dysfunction that resolved with defibrotide. At last follow up, peripheral T and myeloid chimerisms exceeded 90% in all 4 patients. Average time to CD4 recovery (> 200x106/L) was 142 days. Pre-existing inflammatory bowel disease in CGD (n=1) and WAS (n=1) patients resolved immediately following transplant. There was no graft failure, and none developed Grade III-IV acute or extensive chronic GVHD. Patient with WAS developed recurrent autoimmune cytopenias requiring corticosteroids, rituximab, sirolimus and daratumumab, and ultimately resolved. Viral reactivations included EBV (n= 1), adeno (n= 1), HHV6 (n= 2), BK (n=1), norovirus (n=1), and late HSV (n=1), all responded to antivirals without disease. All patients acquired SARS-Cov-2 after transplant and recovered without sequelae. Conclusion(s): TCR alphabeta+ and CD19+ depleted haploidentical transplantation using a reduced toxicity conditioning regimen with pharmacokinetic guided busulfan, fludarabine, thiotepa and thymoglobulin is well-tolerated in young children with PIDD that results in rapid, durable engraftment with low likelihood of GVHD and graft rejection.Copyright © 2023 American Society for Transplantation and Cellular Therapy
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Introduction: Access to kidney transplantation has always been a problem in the African countries with many patients having to travel to other medically advanced countries in Asia, Europe and America. This involves unnecessary excessive expenditure and the travails of journey and stay in an unknown foreign land. To ease this situation and to provide affordable Renal transplant services in their home land, we have made an effort to start the transplant services at our medical facility and have successfully carried out about 275 transplants over a period starting from Nov 2018 till September 2022. Method(s): All the Kidney transplants done between the period Nov 2018- September 2022 (275 cases) were included in the analysis. All the transplants were performed at a single center and the data were collected progressively during their Pre transplant evaluation, perioperative course and post op follow up. All the laboratory and radiological tests were done locally at the center except the HLA cross matches and tissue typing, which were outsourced to Transplant immunology labs outside the country. All the patients with positive DSA titres [about 70%], underwent Plasmapheresis and received IVIg before the transplantation. immunological assessment was done by NGS high resolution, for A B C DP DQ DR loci and X match was done by SAB analysis for class 1 and Class II antigens. All the patients underwent laparoscopic donor nephrectomy. All Patients received vaccinations for Hepatitis B, Pneumonia, Infuenza & Covid. Result(s): A series of 275 kidney transplants were performed over a period of 42 months [ Nov 2018- September 2022] at a private hospital successfully. All the cases were live donor kidney transplants with majority of the donors being 1st or 2nd degree relatives or spousal donors. About 70% of the patients had some degree of sensitization in the form of weakly positive B cell X match, or positive for DSAs at CL I, CLII with MFIs > 1000. All high-risk patients received induction with rabbit Thymoglobulin, and IV methyl prednisolone. Around 50 patients received Basiliximab. Of all patients, 4were HBsAg positive, and 6 were HIV positive,& HCV 1 patient. 8 patients required pretransplant Parathyroidectomy for refractory hyperparathyroidism, 3 patients required simultaneous native kidney nephrectomy at the time of transplant. 25 patients had multiple renal vessels which were double barreled and anastamosed.4 patients had lower urinary tract abnormalities requiring simultaneous/subsequent repair. Overall, 4 patients underwent 2nd transplant. All the donors underwent laparoscopic nephrectomy. Most of the patients had good immediate graft function except in 40 patients, who had delayed graft function;most of them improving over 2 - 6 weeks. 6 Patients had hyperacute rejection and the graft was lost,.4patients had main renal artery thrombosis, Renal allograft biopsy was done in 20 patients. Overall, the Patient survival was 95 %.at 1 year and graft survival 90%. Conclusion(s): Our experience shows that kidney transplantation is a viable and practical option for End stage kidney disease and can be performed even in resource constrained centers in third world countries and the survival rates of patients and the grafts are comparable to other centers across the world. No conflict of interestCopyright © 2023
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Introduction: Kidney transplantation is the best treatment option for patients with end-stage kidney diseases. Quality and longevity of life are better with kidney transplant than chronic dialysis. Kidney paired donation and ABO incompatible kidney transplant (ABOiKT) are among the strategies to expand the living donor pool to overcome shortage of organs. Although first ABOiKT done in 1951 by Hume et al. was an unsuccessful attempt;Alexander et al. in 1987, proposed desensitization protocol with successful ABOiKT. Advancements in desensitization protocols have resulted in increasing success with ABOiKT. In developing countries like India, numbers of ABOiKT are steadily increasing. Aim of this study was to assess short term outcome of ABOiKT and their comparison with ABO compatible kidney transplant (ABOcKT). Method(s): This was a single center prospective observational study done over a period of 2 years. All the living donor kidney transplants including both ABOcKT and ABOiKT done between September 2020 to August 2021 at Jaslok Hospital and Research Center, Mumbai were included in this study. All ABOiKT recipients underwent pre-transplantation desensitization with injection rituximab and plasmapheresis. Pretransplant isoagglutinin titer of <= 1 : 8 was considered acceptable. Inj. Antithymocyte globulin (ATG) (1mg/kg), Inj. Anti-T lymphocyte globulin (ATLG) (3 to 5 mg/kg) or Inj. Basiliximab (20mg 2 doses 4 days apart) was used as induction agent. Triple immunosuppression regimen of prednisolone, tacrolimus and mycofenolate mofetil was started 7 days prior to transplant in ABOiKT and 2 days prior to transplant in ABOcKT and continued in post-transplant period. Valganciclovir was given to all patients for Cytomegalovirus (CMV) infection prophylaxis for 6 months. All the transplant recipients were followed up at 0, 3, 6, 9 and 12 months after transplant and in between when clinically indicated. Data collected was analyzed at the end of 1 year for outcomes of rejection episodes, graft dysfunction, graft loss, infections and death. Result(s): Total 95 patients were included in study, 29 (30.5%) out of them were ABOiKT recipients. Mean (SD) age of study population was 37.8 (+/- 10.5) years. Blood group B to B was the most common ABOcKT and B to O was the most common ABOiKT. Highest baseline isoagglutinin titer was 1:1024.There was no significant difference for rejection episodes, graft dysfunction, graft loss and death in ABOiKT and ABOcKT groups. Urinary tract infection was the most common infection in post-transplant period. COVID-19 was most common viral infection followed by CMV infection. Bacterial infections and overall infections were significantly higher in ABOiKT recipients (p value 0.001 and 0.006 respectively) but severe infections requiring hospitalizations and ICU care were not significantly higher. Two deaths occurred during our study, one in each group. One death was related to COVID-19 infection and second was because of pulmonary mucormycosis. Conclusion(s): Contrary to belief, ABOiKT has non inferior short term outcomes when compared with ABOcKT. Though in our study, bacterial infections were significantly higher in ABOiKT recipients, severe infections requiring hospitalization and ICU care were not increased. ABO incompatible kidney transplantation is an effective modality to increase donor pool and can be applied more widely. No conflict of interestCopyright © 2023
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Introduction: Anti Thymocyte Globulin(ATG) is very effective as an Induction and antirejection therapy (ART) agent in renal Transplantation. Equine ATG (eATG) has been used less compared to rabbit ATG(rATG) in tranplantation. Cost of eATG as induction agent is 200 USD, in comparison to rATG, which costs minimum 700 USD per dose (approximately four times more than eATG). Experience with eATG initially was not good because of drug reactions but over the years the molecule has evolved into a better drug and is the preferred drug over rATG in severe Aplastic Anemia without any reactions. Covid pandemic has affected the supply chain of rATG because of vaccine production leading to shortage of rATG. Hence eATG is the only available ATG. Method(s): We present our experience with eATG in a tertiary care nephrology centre for the last 95 renal transplants. Patients have been divided into two groups. Group A- contained HLA matched first degree relatives as renal donors and induction agent was injection Methylprednisolone (MP). Group B- Had Recipients of Deceased or Spousal donors and received eATG 10mg/kg as induction agent single dose. Monitoring of renal function and observation for complications including, infections was done. Blood lymphocyte count was monitored for intial 2 weeks to look for lymphocyte depletion as an indicator of eATG efficacy. Patients were followed upto 5 years post transplant (PTX) and assessment was done at 1,3 and 5 years for graft and patient survival. eATG usage as anti rejection therapy (ART) agent in acute T- cell-mediated rejection(TCMR) : All acute TCMRs (biopsy proved) were treated with eATG 10mg/kg body for 5 consecutive days followed by repeat biopsy and additional eATG therapy depending on patient response. Result(s): Induction Therapy: Table 1,2,3 Number of recipients in GrA were 41 and GrB were 54. Marked decrease in Lymphocyte count in Gr B indicated efficacy of eATG (p<0.05). In the first 90 days post transplant, Acute TCMR ( biopsy proved) was seen in 5(9.7 %) of GrA and 7(12.9 %) of GrB (p>0.05). In GrA 1(2.4%) patient had acute antibody mediated rejection (ABMR) but could not be treated with ART because of presence of active infection. In Gr B 1(1.8%) patient had histopathological features suggestive of ABMR but was C4D negative and patient responded to eATG alone. Infections were noticed in 9.7% (5/41) of GrA patients and 11.1% (6/54) of GrB patients in the first 180 days PTX (p>0.05). Urinary tract infections, respiratory tract infections and soft tissue infections were commonly seen. Post ART oppurtunistic infections were not seen. Comparison of incidence of Acute rejection rates, graft survival, complications rate and patient survival rate show similar results in both the groups. We achieved good efficacy with eATG as induction and ART agent in biopsy proved acute TCMR. No adverse events and no malignancies were observed after eATG therapy. Conclusion(s): eATG can be used as induction and antirejecton therapy agent in TCMR in renal transplantation. eATG is economical compared to rATG. No conflict of interestCopyright © 2023
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Case Report: A 48y/o man with a history of ESRD secondary to FSGS was found to have hepatitis-C virus (HCV) reactivation after kidney transplantation (KT) with an HCV-positive allograft. The patient was HCV-negative before transplantation in July 2021. He was negative for hepatitis-B virus (HBV) core antibodies but had evidence of prior HBV vaccination and was negative for HIV 1/2. His induction therapy included thymoglobulin, and his maintenance immunosuppressive regimen included mycophenolate mofetil (MMF), tacrolimus, and prednisone. Aweek after KT, the patient tested positive for HCV genotype 1a, and he was started on sofosbuvir/velpatasvir in August 2021. Lab monitoring showed decreasing levels of HCV viral load (VL) until it was undetectable 2 months later. In January 2022, renal function remained stable, and urinalysis and hepatic function tests remained unremarkable. However, HCV viral load was positive in February 2022 and the HCV genotypewas 1a, as before. This result raised the possibility of reactivation of HCV from his allograft more than 6 months post KT. Additionally, despite negative BK polyoma VL initially, he was positive in January 2022 and discontinued his MMF. He was also positive for COVID-19 in January 2022 as well. Given his recurrence of HCV VL, he initiated sofosbuvir/velpatasvir/ voxilaprevir in April 2022 and completed therapy in July 2022, and maintained sustained viral response (SVR) as of October 2022. His BK VL was negative in May 2022. Recent guidelines on preventing HCV reactivation in allograft-positive KT recipients state that individuals should achieve SVR after 8-12 weeks of a course of direct-acting antiviral (DAA) therapy. The patient completed DAA therapy post-transplantation with a successful negative viral load 2 months later. However, he did not achieve SVR because his VL was again positive 3 months after completion of therapy. Reactivation of BKV, a DNA virus that establishes lifelong infection in renal tubular and uroepithelial cells, is common among KT recipients, but there is insufficient evidence to establish a causal association between BKV reactivation and HCV reactivation. There is no consensus on a chemotherapeutic maintenance regimen to prevent HCV reactivation. This case highlights the importance of close follow-up monitoring for HCV and BKV among KT recipients and the need to explore the relationship between BKV reactivation, HCV reactivation, and immunosuppression regimen. Copyright © 2023 Southern Society for Clinical Investigation.
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Purpose: The purpose of this study was to assess the clinical characteristics of serologic non-responders to COVID-19 booster vaccination in a cohort of solid organ transplant recipients. Method(s): All solid organ transplant recipients our center who received COVID-19 booster vaccination and had SARS-CoV-2 Spike IgG antibodies checked at least 4 weeks after the dose were included. We evaluated the patients who were found to have negative SARS-CoV-2 Spike IgG antibodies despite booster vaccination (i.e. serologic non-responders). Result(s): Among 657 solid organ transplant patients who had received a booster COVID-19 vaccination, 168 patients had Spike IgG antibodies checked during the study period. Forty-nine patients (29.2%) were found to be seronegative and were included in the analysis. 69% were male with a median age of 60 years. The majority of the cohort (47%) were kidney transplant recipients who had received primary vaccination series at a median of 206 days post-transplant. 65% had received basiliximab for induction immunosuppression. Most of the patients (65%) received primary vaccination with Pfizer COVID-19 vaccine and 67% received Pfizer COVID-19 booster vaccination at a median of 187 days after primary vaccination series. Spike IgG antibodies were checked at a median of 41 days from booster vaccination. No patients received rATG within 90 days of booster administration. Similarly, no patients received high dose (>250mg methylprednisolone equivalent) steroids within 30 days prior to booster vaccination. For immunosuppression, 27% were maintained on belatacept and 82% were on anti-metabolites at the time of the booster vacciantion. Ten patients (20%) experienced a COVID-19 infection postcompletion of their booster vaccination. Conclusion(s): In our solid organ transplant cohort, the majority of serologic nonresponders underwent basiliximab induction and were on an antimetabolite for maintenance immunosuppression. A limitation of our study was the use of different laboratory assays for determining IgG levels. Future work includes evaluating the clinical characteristics of COVID 19 booster serologic responders and comparing the two populations. (Table Presented).
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Purpose: To evaluate the efficacy and safety of a protocol increasing the net state of immunosuppression for adult kidney transplant recipients (KTR) with delayed graft function (DGF). Method(s): Single-center retrospective cohort of adult KTR with DGF transplanted from January 2017 to March 2021. Pre- vs post-DGF protocol implementation outcomes were evaluated. Protocol included cumulative 6 mg/kg rabbit antithymocyte globulin (rATG) induction, non-weight-based mycophenolate mofetil dosing (1000 mg bid), and higher goal tacrolimus trough (9-12 ng/mL). Pre-protocol patients received cumulative 4.5 mg/kg rATG. Efficacy outcomes were biopsy proven acute rejection (BPAR) and graft loss at 6 months. Safety outcomes were incidence of cytopenia, infection, and all-cause readmission at 6 months. Result(s): Eighty-nine DGF patients met inclusion criteria. Baseline characteristics were similar between groups, with median age (57+/-19) years and majority Hispanic (42.7%) males (61.8%) with a negative crossmatch (100%). Most post-protocol patients received 6 mg/kg cumulative rATG induction (71.4%) and mycophenolate mofetil 1,000 mg bid (80.3%) with therapeutic tacrolimus troughs by discharge (64.3%). Significantly less BPAR was observed post-protocol (7/56, 12.5% vs 10/33, 30.3%;p = 0.04). Of those with BPAR, significantly less post-protocol patients experienced T-cell mediated rejection (TCMR) than pre-protocol (2/7, 28.6% vs 9/10, 90.0%;p = 0.03). However, antibody-mediated (4/7, 57.1% vs 1/10, 10%) and mixed (1/7, 14.3% vs 0%) rejection were more frequent post-protocol (p = 0.10 and 0.41, respectively). Graft loss was similar post- vs pre-protocol (5/56, 8.9% vs 0;p = 0.16). All post-protocol graft losses were due to death (4 from COVID-19 and 1 unknown). Safety outcomes were similar between groups (Table 1). Conclusion(s): An increased net state of immunosuppression in DGF KTR significantly lowered the 6-month incidence of BPAR without significantly affecting safety. TCMR incidence was significantly decreased, but displaced by antibody-mediated and mixed rejection, implying need to conduct further prospective studies of larger sample sizes. Given majority of graft losses were due to COVID-19 pneumonia, studies are needed to evaluate the risk of COVID-19 infections in DGF KTR, especially with the availability of vaccines. (Table Presented).
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Purpose: During the COVID-19 pandemic, many transplant centers modified induction immunosuppression regimens. Beginning December 2020, our center reduced anti-thymocyte globulin (ATG) protocol dosing by up to 33% compared to the pre-pandemic doses (7.5, 4.5, and 3mg/kg, per immunologic risk) for all recipients, with no change in maintenance immunosuppression. We examined the impact of reduced ATG dose on kidney allograft and transplant recipient outcomes. Method(s): We retrospectively reviewed adult recipients who received a kidney transplant between December 2020 and March 2021 (pandemic) with a minimum of 6 months follow up post-transplant, and recipients who received a transplant between January 2019 and December 2019 (pre-pandemic). We chose 2019 as a comparable pre-pandemic cohort as they were treated without influence from the COVID-19 pandemic. We ed patient demographic and laboratory data from electronic health records. We excluded multi-organ transplant recipients. Result(s): 78 adult kidney transplants were performed during the pandemic era and 211 were performed during the pre-pandemic era. The characteristics of the two cohorts are illustrated in Table 1. The primary outcomes are illustrated in Figure 1. The rate of biopsy proven rejection (including surveillance and for-cause biopsies) did not increase during the pandemic as compared to pre-pandemic era (6.3% vs 8.0%, respectively, p=0.8). The rate of BK viremia (>1000 copies/mL) at 3 months was lower in the pandemic era, but not statistically significant (6.4% vs 8.7%, respectively, p=0.6). The rate of delayed graft function (DGF) was significantly higher in the pandemic era compared to pre-pandemic (42.3% vs 22.9%, respectively, p=0.002). No recipients tested positive for COVID-19 within 1-month of transplant. Conclusion(s): Despite the reduction in ATG dose, we found no significant change in the rate of rejection or infection. We did however find a significant increase in the rate of DGF during the pandemic era. Further studies are needed to assess the long-term effects of reduced induction immunosuppression regimen on kidney transplant recipients. (Figure Presented).
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Purpose: The COVID-19 pandemic portends significant morbidity and mortality in immunocompromised individuals. Vaccination against COVID-19 among immunocompromised population is an essential step to minimize deadly complications. Numerous studies have shown an association between immune status, disease severity, and suboptimal responsiveness to vaccination. Additionally, data suggests that elevated IgG levels correlated with host viral neutralization. We herein present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to vaccination among kidney transplant recipients. Method(s): The study data was retrospectively analyzed for 48 kidney transplant patients who received mRNA type COVID-19 vaccine at our institution. Majority of patients received vaccination between January and March 2021;two doses in total. The 30 days post-vaccination SARS-CoV-2 spike antigen-specific IgG levels were measured to assess immunological response to vaccine. Result(s): The included patients underwent kidney transplantation between 1983 and 2020. Among these patients, 35% showed detectable peak COVID IgG serum levels 30 days after the 2nd vaccine dose. A total of 31 patients (65%) did not show any response;majority of these non-responders (62%) were heavily immunocompromised, either on high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus+/-Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. Among immunocompetent patients, over 95% immunological responsiveness or viral neutralization after the second vaccination dose has been reported. Conclusion(s): Anti-thymocyte globulin as induction immunosuppression and antimetabolites like Mycophenolate as maintenance immunosuppression serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation, thereby reducing antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. The ability of these immunosuppressive medications to suppress responsiveness to the SARS CoV-2 vaccine supports the need for 1) regular immunological surveillance post-vaccination among transplant patients, and 2) the need for a third or possibly fourth booster dose to achieve a sustained and effective response.
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Purpose: The purpose of this study was to assess treatment of coronavirus disease 2019 (COVID-19) and immunosuppression modification in solid organ transplant (SOT) recipients, and identify risk factors that contribute to mortality among SOT recipients with COVID-19. Method(s): The primary endpoint was 90-day mortality. Secondary endpoints include COVID-19 treatment regimen, laboratory abnormalities, maintenance immunosuppression modification, concomitant infections, complications such as renal replacement therapy (RRT) and more. This retrospective chart review included all SOT recipients who presented to our institution with a positive COVID-19 test over an 18-month period. Dual organ transplant recipients were excluded. Result(s): A total of 112 patients met inclusion criteria. The average age was 56 +/- 13 years and 58% of patients were male. The majority of patients identified as Latino (39%), followed by African-American (29%) and Caucasian (28%). Forty-nine percent required treatment in the intensive care unit. Inflammatory markers were elevated in the majority of patients. Most immunosuppression modification strategies held antimetabolites and prednisone if receiving treatment with glucocorticoids. The primary endpoint of 90-day mortality was observed in 24% (27/112) of patients. Mortality rates by organ type can be found in Table 1. Common comorbidities in these patients are depicted in Figure 1. There was no significant difference in mortality between patients receiving remdesivir 12/27 vs. 20/85 (p=0.05). A 50% (4/8) mortality rate was observed among patients who received rabbit antithymocyte globulin within 6 months of COVID-19 infection (p=0.09). Concomitant respiratory infections showed a statistically significant difference in mortality 12/27 vs. 9/85 (p<0.05). All 6 patients that required extracorporeal membrane oxygenation expired. Fifty-two percent (14/27) of patients in the mortality group required RRT vs. 7% (6/85) of those that survived (p<0.05). While most cases were prior to the advent of COVID-19 vaccines, all 9 patients that received at least one dose of any COVID-19 vaccine prior to infection survived at 90 days. Conclusion(s): Concomitant respiratory infections and RRT were significant predictors of mortality among SOT recipients with COVID-19. Administration of rabbit antithymocyte globulin within 6 months of COVID-19 infection and treatment with remdesivir should be investigated in future studies as they may demonstrate significant associations in a larger sample size.
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Purpose: Infectious complications are a major cause of mortality and morbidity after kidney transplantation. During the COVID-19 pandemia there were several changes in the management and behavior of patients after transplant. These included measures such as universal masking, social distancing and reinforcing hand hygiene. Our objective was to evaluate if these differences affected the incidence of infections after kidney transplant. Method(s): This is a retrospective cohort study of all kidney transplants performed in our institution from March 2017 to November 2020. We examined the incidence of wound infection, urinary tract infection (UTI), pneumonia, and gastrointestinal (GI) infections. Pediatric and multi-organ transplants were excluded. We used the Fisher test, Chi-squared test of independence and logistic regression models in the analysis. All tests were based on a level of significance of alpha=0.05. Result(s): A total of 185 deceased donor kidney transplant patients were reviewed, 153 before and 54 after the beginning of the COVID-19 pandemic in the United States. The incidence of wound infection, pneumonia and GI infection were similar before and after COVID (Table 1). There was a significant increase in UTI after the COVID pandemic, the main organisms isolated were Klebsiella pneumonia (50%) and E. coli (25%). Overall the presence of UTI and wound infection were significantly related (OR 4.2, p = 0.06). Other clinical variables such as age, BMI, KDPI, EPTS, and the occurrence of delayed graft function were not associated with UTI. COVID infection was present with similar incidence: 12% in patients transplanted before and 14.8% in patients transplanted after the onset of the pandemic. Induction with Thymoglobulin or Basiliximab was not significantly different before and after COVID, and the choice of induction was not associated with the rate of UTI. Conclusion(s): While multiple changes in the management of patients and patient behavior are different before and after the onset of the COVID-19 pandemic, this analysis did not find significant change in the incidence of infections except for UTI in comparative cohorts of kidney transplant recipients. This study did not identify specific factors associated with the increase of UTI in our population. However, in response certain measures were implemented, such as reducing the time to ureteral stent removal and giving 24 hrs of prophylactic antibiotics at the time of stent removal.
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Purpose: COVID-19 pandemic has had a significant impact on access to routine healthcare in both hospitalized and out-patient settings. This impact was also noted in various aspects of pre and post-transplant care of liver transplant (LT) recipients. The aim of our study was to analyze the direct and indirect impact of COVID-19 on mortality in patients with recent LT. Method(s): We retrospectively analyzed 30-day, 6-month and 1-year mortality data from the UNOS database in adult LT recipients from 3 distinct groups;Pre-COVID (March 11- September 10, 2019: LT and immediate follow-up care before pandemic), Para-COVID (September 11- March10, 2020: LT before pandemic and follow-up care during pandemic), and COVID (March 11- September 10, 2020: LT and follow-up care during pandemic). Result(s): 12,598 LTs were performed during the study period. During COVID period, there was increase in LT for alcoholic liver disease, average MELD score was higher, LT for hepatitis C decreased, use of thymoglobulin induction decreased and waiting time was shorter. During the 30-day period, overall mortality between 3 groups remained same. In the COVID group, mortality from graft failure was higher (7.4 vs 17.9%, p=0.07), rate of infection was lower (14% vs 4.2%, p=0.039), and incidence of graft rejection prior to discharge was higher. During the 6-month follow-up, overall mortality, mortality from malignancy and COVID, and graft failure increased significantly in the COVID group. During the 1-year follow-up period, mortality was highest in COVID group over para-COVID group and lowest in the pre-COVID group. In the COVID group, increased mortality was from graft failure and COVID. Overall mortality in the study cohort directly from COVID was 7.8%, which was highest in the COVID group. Multivariable cox regression for one year mortality showed that risk factors for mortality were COVID period [Hazard Ratio (95%CI) 1.22 (1.02-1.46), p=0.027], older age of recipient, diabetes, portal vein thrombosis, ventilation at the time of transplant, hemodialysis at the time of transplant, re-transplant, and prolonged cold ischemic time. Conclusion(s): COVID-19 significantly impacted LT short term outcomes with increased mortality seen from COVID directly as well as indirectly. During COVID, cautious and lower use of immuno-suppression was likely associated with higher rates of rejection and lower rates of infection. Disruptions in routine post-transplant follow-up likely contributed to increased death from graft failure, malignancy, and poor control of chronic medical conditions like diabetes. (Figure Presented).
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Purpose: Transplant volumes decreased significantly during the first months of global pandemic of COVID-19, followed by a shift in the standard of care of transplant medicine. It has become widely accepted to rigorously screen and test donors and recipients for COVID-19 before proceeding with transplant. Discarded kidneys due to positive COVID-19 testing in potential donors is a new challenge for transplant centers. The emerging vaccines and lines of therapy have given us tools that could be utilized to re-balance the shift in practice and maximize organ utilization. Method(s): In this we present two cases of kidney transplantation from a COVID-19 positive deceased donor. The first recipient was a 40-year-old female who has been vaccinated with two doses of mRNA-1273 vaccine five months before transplant. The second patient was a 41-year-old male without a prior COVID-19 vaccine, he had a natural infection with COVID-19 about 10 months prior to transplant, and antibody was positive for anti-nucleocapsid IgG at the time of transplantation. Both recipients had negative SARS-CoV-2 nasopharyngeal swab PCRs prior to transplantation, and both received induction with anti-thymocyte globulin 5mg/ kg. Both recipients received their transplanted kidneys from the same donor, who tested positive by RT-PCR for COVID-19 from a nasopharyngeal swab three days prior to procurement (Roche Cobas Liat PCR, single cycle threshold). On the following day, the donor's bronchial washing was negative. At the day of procure662 Kidney Deceased Donor Selection ment, repeated PCR from a nasopharyngeal swab was negative, and COVID-19 antibody was positive for anti-nucleocapsid IgG (AbbottTM ARCHITECTTM). The donor cause of death was head trauma with a terminal serum creatinine of 0.3mg /dL Chest imaging did not demonstrate COVID-19 pneumonitis. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin as post-exposure prophylaxis. Result(s): Both recipients had an appropriate renal allograft function. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin. Both recipients demonstrated no signs or symptoms of COVID-19 infection during their hospitalization and were instructed to maintain 14 days of COVID-19 exposure precautions post-discharge. At 12 weeks from transplant, both patients had no symptoms of COVID-19 infection. SARS-CoV-2 RNA has been detected in several organs including kidney, but there was no proof of infective virus in extrapulmonary organs. Conclusion(s): These two cases may broaden the scope of accepting organs from COVID-19 positive deceased donors and the use of casirivimab and imdevimab for immediate post-transplant surgery prophylaxis. While we are not sure if the monoclonal antibodies did offer any benefits here, we think that this report may throw the light on its potential use in post-transplant surgery prophylaxis. Further studies are warranted to examine the benefits of such practice.
ABSTRACT
Purpose: Viral infections (VI) commonly occur in the post-transplant period and higher cumulative doses of rATG have been correlated with higher rates of infection. However, basiliximab (BAS) has decreased risk of infection but increased risk of rejection due to a lower immunosuppressive profile. There is a shortage of literature evaluating choice and dosing of induction agent and the incidence of VI in kidney transplant recipients (KTR) receiving tacrolimus, mycophenolate and early steroid withdrawal. This study evaluated the incidence of VI in KTR receiving BAS, rATG low (< 3mg/kg), or high dose (> 3mg/kg) within 180 days post-transplant. Method(s): This single-center, retrospective study included adult KTR from July 2020-March 2021. KTR were excluded if they received a multi-organ transplant, no induction, or maintenance immunosuppression other than tacrolimus and mycophenolate. Induction was given based on patients' immunologic risk factors for rejection which included: age, race, cPRA, retransplantation, and DR HLA mismatch. The primary objective compared the incidence of VI with BAS, rATG low and high dose. Secondary outcomes included incidence of CMV, BKV, EBV, HSV, COVID-19, DGF, BPAR, de novo DSA, eGFR, tacrolimus levels, graft loss, and mortality within 180 days post-transplant. Result(s): There were 44 KTR who received BAS, 43 who received low rATG dose, and 129 who received high rATG dose. Statistically significant differences in baseline demographics included age, race, mean peak cPRA, and mean KDPI (due to institutional induction guidelines) [Table 1]. A larger proportion of high rATG patients experienced VI, followed by low rATG patients, p<0.01 [Table 2]. Increased incidence of CMV, BKV, and COVID-19 occurred in patients receiving rATG [Table 2]. Infections generally occurred earlier in the rATG groups [Table 2]. DSA was highest in the high dose rATG (14%) which was attributed to high risk factors for rejection, p=0.0146 [Table 3]. No differences in BPAR, DGF, graft failure, or mortality were seen between all groups within 180 days. Conclusion(s): KTR that received induction with any rATG dose had a higher incidence of viral infections compared to basiliximab. Induction with rATG may lead to an earlier onset of viral infections compared to basiliximab. Further review of data at one year post-transplant is planned to strengthen the results of this study.
ABSTRACT
Purpose: Rabbit anti-thymocyte globulin (rATG) is a polyclonal antibody utilized for induction immunosuppression in high immunologic risk kidney transplant recipients. However, the optimal total dose of rATG has not been identified. Higher cumulative doses of rATG may be associated with an increased risk of adverse infectious and hematologic outcomes, while lower cumulative doses may not provide adequate immunosuppression to prevent acute rejection. In March 2020, the total rATG dose in our institution's induction protocol for kidney transplant recipients was reduced from 6 mg/kg to 4.5 mg/kg to avoid potential infectious complications from COVID- 19. The objective of this study is to compare the efficacy and safety between two different doses of rATG. Method(s): This was a single center, retrospective chart review of adult kidney transplant recipients who received rATG for induction between September 1, 2019 and August 31, 2020. Patients who received a total dose of 6 mg/kg rATG were compared to patients who received a total dose of 4.5 mg/kg. The primary outcome was biopsy proven acute rejection (BPAR) within 90 days of transplant. Secondary outcomes assessed incidence of infection, leukopenia, neutropenia, thrombocytopenia, and delayed graft function within 90 days of transplant. Result(s): Eighty-one adult kidney transplant recipients were included in this study;37 received 6 mg/kg of rATG and 44 received 4.5 mg/kg of rATG. Incidence of BPAR was significantly lower in the 6 mg/kg rATG group compared to the 4.5 mg/ kg group (2.7% vs 20.5%, p=0.02). The majority of rejection episodes were classified as borderline. Patients who had BPAR were treated with corticosteroids. The number of patients who had an infection was significantly lower in the 6 mg/kg group compared to 4.5 mg/kg group (21.6% vs 47.7%, p=0.02). There was a numerically lower incidence of delayed graft function in the 6 mg/kg group compared to the 4.5 mg/kg group (25.0% vs 43.2%, p=0.18). Incidence of leukopenia, neutropenia, and thrombocytopenia were similar between groups. Conclusion(s): In conclusion, a lower cumulative dose of rATG was associated with an increased risk of borderline rejection and a numerically higher incidence of delayed graft function.