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SOT Recipients (sot + recipient)

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Medical Sciences	100%

Selected Abstracts

Clinical Predictors of Relapse after Treatment of Primary Gastrointestinal Cytomegalovirus Disease in Solid Organ Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
A. J. Eid
Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R, SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40,70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean ± SD, 33.8 ± 19.3 days) followed by valganciclovir (27.5 ± 13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6 ± 28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5,30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0,33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p = 0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse. [source]

Adoptive T-Cell Therapy of a Lung Transplanted Patient with Severe CMV Disease and Resistance to Antiviral Therapy

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
G. Brestrich
Infections with cytomegalovirus (CMV) can induce severe complications after transplantation, particularly in patients resistant to virostatic therapy. Adoptive transfer of CMV-specific T-cell lines has demonstrated promising results in patients after hematopoietic stem cell transplantation. However, the generation of specific T-cell lines ex vivo and their function in vivo is complicated in solid organ transplant (SOT) recipients. Here, we present the successful adoptive transfer of autologous CMV-specific T cells to a lung transplant recipient with ganciclovir-resistant CMV-pneumonia requiring mechanical ventilation. Infused T cells rapidly expanded in vivo and efficiently inhibited viral replication as confirmed by extensive longitudinal immunological monitoring. After full recovery, the patient was released from the clinic. After 4 weeks, the infection reappeared and persisted at a low level even after a second T-cell infusion. Our experimental data indicate that this could be the consequence of the late differentiated phenotype of the infused T cells and therefore their insufficient longevity in vivo. In summary, our report signifies the high therapeutic potential of adoptive immunotherapy in the treatment of SOT recipients when all other measures show no effect. Further studies have to elucidate the most potent strategies to generate antigen-specific T cells with high functional capacity and robust long-term persistence. [source]

Long-Term Outcomes of CMV Disease Treatment with Valganciclovir Versus IV Ganciclovir in Solid Organ Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
A. Åsberg
Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long-term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 [1.3,11.3], p = 0.012; virological: OR 5.6 [2.5,12.6], p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long-term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment. [source]

Incidence Rate and Outcome of Gram-Negative Bloodstream Infection in Solid Organ Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009
M. N. Al-Hasan
Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram-negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram-negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram-negative BSI was observed within the first month following SOT (210.3/1000 person-years [95% confidence interval (CI): 159.3,268.3]), with a sharp decline to 25.7 (95% CI: 20.1,32.1) and 8.2 (95% CI: 6.7,10.0) per 1000 person-years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram-negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9,13.1] vs. 5.2 [95% CI: 3.1,7.8] per 1000 person-years). The overall unadjusted 28-day all-cause mortality of Gram-negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy. [source]

Valganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
W. Vaudry
Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients ,2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 × body surface area × creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 ± 11.9 ,g * h/mL; liver 61.7 ± 29.5 ,g * h/mL; heart 58.0 ± 21.8 ,g * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults [source]

Prevention of toxoplasmosis in transplant patients

CLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2008
F. Derouin
Abstract Toxoplasmosis is a life-threatening opportunistic infection that affects haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. Its incidence in these patients is closely related to the prevalence of toxoplasmosis in the general population, which is high in Europe. In SOT recipients, toxoplasmosis results mainly from transmission of the parasite with the transplanted organ from a Toxoplasma -seropositive donor to a Toxoplasma -seronegative recipient. This risk is high in cases of transplantation of organs that are recognized sites of encystation of the parasite, e.g. the heart, and is markedly lower in other SOT recipients. Clinical symptoms usually occur within the first 3 months after transplantation, sometimes as early as 2 weeks post transplant, and involve febrile myocarditis, encephalitis or pneumonitis. In HSCT recipients, the major risk of toxoplasmosis results from the reactivation of a pre-transplant latent infection in seropositive recipients. The median point of disease onset is estimated at 2 months post transplant, with <10% of cases occurring before 30 days and 15,20% later than day 100. Toxoplasmosis usually manifests as encephalitis or pneumonitis, and frequently disseminates with multiple organ involvement. Diagnosis of toxoplasmosis is based on the demonstration of parasites or parasitic DNA in blood, bone marrow, cerebrospinal fluid, bronchoalveolar lavage fluid or biopsy specimens, and serological tests do not often contribute to the diagnosis. For prevention of toxoplasmosis, serological screening of donors and recipients before transplantation allows the identification of patients at higher risk of toxoplasmosis, i.e. seropositive HSCT recipients and mismatched (seropositive donor/seronegative recipients) SOT recipients. Preventing toxoplasmosis disease in those patients presently relies on prophylaxis via prescription of co-trimoxazole. [source]

Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients

CLINICAL TRANSPLANTATION, Issue 5 2005
Sean Garrean
Abstract:, Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart,lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving. [source]