Measles, Mumps, Rubella, and Varicella Zoster Virus Serology and Infections in Solid Organ Transplant Recipients During the First Year Posttransplantation

2020 ◽  
Author(s):  
Omid Rezahosseini ◽  
Søren Schwartz Sørensen ◽  
Michael Perch ◽  
Christina Ekenberg ◽  
Dina Leth Møller ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Varicella Zoster ◽  
Severe Infections ◽  
One Year ◽  
A Prospective Study

Abstract Background Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients. Methods This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection. Results Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR. Conclusions A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT.

scholarly journals Incidence and Outcomes of Post-Transplant Lymphoproliferative Disease after 5365 Solid Organ Transplants over a 20 Year Period at 2 UK Transplant Centres

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 888-888
Author(s):  
Anna Santarsieri ◽  
Andrew Butler ◽  
William Gelson ◽  
Stephen Pettit ◽  
John F Rudge ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
First Year ◽  
Solid Organ ◽  
Line Treatment ◽  
First Line ◽  
Post Transplant

Abstract Background: Post-transplant lymphoproliferative disease (PTLD) confers a high morbidity and mortality in a vulnerable population. We present the epidemiology and outcomes of PTLD in a large UK cohort of solid organ transplant (SOT) recipients who were transplanted over a 20-year period. Methods: This is a retrospective study of 5365 SOT recipients who had their first transplant between 2000 and 2021 at two UK transplant centres (Addenbrooke's Hospital and Papworth Hospital). We reviewed the records of all patients and found 142 who subsequently developed PTLD. For each type of transplant, we calculated the incidence rate of PTLD and cumulative incidence using a competing risk of death model. Survival was compared with the age-adjusted life expectancy of the UK population using the National life tables and a landmark analysis was performed to compare overall survival (OS) of PTLD patients from the date of diagnosis with the background survival of the transplant population. To compare treatment outcomes, a subset of 90 cases of monomorphic PTLD, DLBCL subtype were identified. 66 were treated with first-line Rituximab monotherapy and 24 received first-line R-Chemotherapy. Demographics, treatment response, and survival data were analysed with univariate and multivariate analysis to identify covariates associated with death in the first year post diagnosis of PTLD. Results: With a median follow-up time of 5.3 years, 142 of 5365 solid organ transplant recipients have developed PTLD (56/1965 kidney, 22/1428 liver, 12/327 simultaneous kidney-pancreas (SPK), 21/113 multivisceral (MVT), 10/778 heart, 15/503 bilateral lung, 3/148 single lung and 3/85 heart and lung). The incidence rate of PTLD was highest in the first year post-transplant in lung and MVT recipients. Cumulative incidence (shown in Figure 1) was 18% at 5 years post-MVT and 1-3% at 5 years following the other SOT types. Cumulative incidence was lowest for liver and heart transplants and was 10% at 20 years post-kidney transplantation. Median OS following SOT was 16 years which is significantly reduced compared with the age-adjusted UK population. There is a relatively high early mortality rate following diagnosis of PTLD and only patients surviving two years post diagnosis regained a similar longer-term survival to the non-PTLD SOT cohort. Treatment with rituximab monotherapy (RM) is now a standard of care for monomorphic PTLD 1. Outcomes for monomorphic patients were compared between those treated with RM (n=66, median follow-up 2.2 y) and R-Chemotherapy (n=24, median follow-up 5.2 y). The two groups were well matched for age and IPI. Of the 66 RM patients, 22 (33%) achieved complete remission with RM and required no further treatment. A further 18 (27%) patients achieved remission following further treatment with chemotherapy/surgery/CTL. 6/66 (9%) patients died of progressive disease (PD), 9/66 (14%) died pre-remission of non-PTLD causes and 11/66 (17%) died in remission of unrelated causes. In the R-Chemotherapy group, 22 patients received R-CHOP and 2 received R-CVP (n=24). 8 (33%) patients are alive and in remission after first line treatment and a further 3 patients (13%) after second line treatment. 2/24 (8%) patients died of PD, 4/24 (17%) died pre-remission of non-PTLD causes and 7/24 (30%) died post-remission of unrelated causes. There is no significant difference in OS between the two groups. Only a minority of deaths were due to PD and death from non-lymphoma causes pre and post remission remain considerably higher than non-PTLD SOT patients up to 2 years post treatment (Figure 1). Multivariate analysis of all 90 monomorphic PTLD patients identified IPI3+ as the strongest pre-treatment variable associating with inferior 1 year OS. Interestingly IPI3+ did not retain this significance when R-chemo patients were analysed alone. Conclusion: With this large SOT dataset we have mapped the cumulative incidence of PTLD over a 20 year period and highlight transplanted organ-specific differences in PTLD incidence over time. Treating monomorphic DLBL patients first-line with RM rather than R-chemotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes pre- and post-treatment remains high with both treatment approaches, with poor OS compared with age-matched non-PTLD SOT recipients. 1Trappe et al. Lancet Oncol; 2012 13(2):196-206 Figure 1 Figure 1. Disclosures Santarsieri: Janssen: Honoraria. Uttenthal: Roche: Other; Takeda: Other; Jazz: Other. Follows: Janssen, Abvie, Roche, AZ: Other.

scholarly journals 572. Antiviral Toxicities Among Pediatric Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S351-S351
Author(s):  
Kevin J Downes ◽  
Anna Sharova ◽  
Marina Mitrou ◽  
Molly Hayes ◽  
Despoina Galetaki ◽  
...  
Keyword(s):  
Medication Management ◽  
Organ Transplant ◽  
Kidney Injury ◽  
Solid Organ Transplant ◽  
Incidence Rates ◽  
First Year ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Disease

Abstract Background Ganciclovir (GCV) and valganciclovir (VGCV) are used for prophylaxis (PPX) and treatment for CMV in pediatric solid organ transplant (SOT) recipients, but the frequency and impact of toxicities from these medications are not well described. Methods Retrospective cohort study of children undergoing SOT at Children’s Hospital of Philadelphia from Jan 2012 - Jun 2018. EMR were reviewed to identify laboratory-based toxicities between 15 days and 1 year post-transplant; medication management within 14 days of toxicity onset was recorded. Toxicities were defined as GCV or VGCV-associated if a patient was on the antiviral at toxicity onset. We defined acute kidney injury (AKI) as ≥50% change in creatinine (Cr) from 30 days prior, leukopenia as WBC < 3500/µL, neutropenia as ANC < 1000/µL, and thrombocytopenia as < 100K/µL. Incidence rates of toxicities on PPX and treatment were compared to rates during no antiviral using univariate Poisson regression. Results 285 children received 299 SOTs: 108 liver, 91 kidney, 69 heart, 31 lung. Nearly half (46%) of toxicities during the first year after transplant occurred while on GCV or VGCV PPX or treatment, but their use accounted for only 23% of all follow-up time. Receipt of VGCV and GCV PPX and treatment were associated with significantly higher incidence rates of toxicities compared to no antiviral (Fig 1). Of 259 GCV or VGCV-associated toxicities, 44% (n=113) were leukopenia, 26% (66) neutropenia, 26% (66) AKI, and 6% (15) thrombocytopenia (Table 1). Most recipients of VGCV PPX (64%) sustained at least one toxicity while on PPX. AKI during VGCV PPX led to stopping/dose-adjusting of VGCV in 43% and of immunosuppression in 57% of cases. Neutropenia during VGCV PPX resulted in stopping/dose-adjusting of VGCV in 63%, of immunosuppression in 36%, and of TMPX/SMX PPX in 36% of cases. During VGCV PPX, 81% of AKI was stage II/III (≥100% change in Cr) and 65% of neutropenia was severe (< 500/µL); 11% of both AKI (n=6) and neutropenia (n=7) during VGCV PPX resulted in hospitalization. Figure 1. Incidence Rates of Toxicities from Day 15 through 1 Year After Transplant Table 1. Antiviral Use and Toxicity 2 Weeks to 1 Year After Transplant Conclusion GCV and VGCV use was associated with significant renal and hematological toxicities in pediatric SOT recipients. While VGCV and GCV are effective at preventing CMV disease in pediatric SOT, clinicians should consider risk of toxicity when evaluating CMV prevention strategies. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

scholarly journals Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

2012 ◽  
Vol 86 (18) ◽  
pp. 10006-10014 ◽  
Author(s):  
Sebastien Lhomme ◽  
Florence Abravanel ◽  
Martine Dubois ◽  
Karine Sandres-Saune ◽  
Lionel Rostaing ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Serum Concentrations

Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lowerKa/Ksratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

scholarly journals 1744. CMV Infection and Management Among Pediatric Solid-Organ Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S639-S639
Author(s):  
Anna Sharova ◽  
Despoina M Galetaki ◽  
Molly Hayes ◽  
Lauren Gianchetti ◽  
Laura A Vella ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Invasive Infection ◽  
Solid Organ ◽  
Cmv Infection ◽  
Research Support ◽  
Free Survival ◽  
Medium Risk ◽  
Cmv Disease

Abstract Background Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT. Methods Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests. Results 244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57). Conclusion CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

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