Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients Treated with a Preemptive/ Targeted Antifungal Therapy Strategy: 4 Year Follow Up

2019 ◽  
Vol 38 (4) ◽  
pp. S220
Author(s):  
S. Herrera ◽  
A. Farooq ◽  
S. Davoudi ◽  
T. Martinu ◽  
D. Kumar ◽  
...  
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5075-5075
Author(s):  
Eli Muchtar ◽  
Liat Vidal ◽  
Ron Ram ◽  
Ronit Gurion ◽  
Yivgenia Rosenblat ◽  
...  

Abstract Abstract 5075 Background: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication after solid organ transplantation. Most cases of PTLD arise within the first year from transplantation and are associated with EBV infection. However, there are increasing reports on a late onset form of PTLD. Methods: We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary center in Israel between the years 1997 and 2012. PTLD was defined according to the WHO criteria. We analyzed baseline characteristics, clinical and pathological parameters as well as transplantation outcomes. Results: We identified 9 PTLD patients among cohort of 336 lung and heart-lung transplant recipients (incidence=2. 7%). Additional PTLD patient from another hospital was added for the clinical analysis (10 patients overall). Median age at transplantation of the PTLD patients was 50 (range 11–63) years, compared to 56 (2–69) among the non-PTLD patients (p=0. 04). Idiopathic pulmonary fibrosis was the leading etiology for transplantation among both PTLD and non-PTLD patients (50% vs. 37. 2%, respectively, p=0. 5), while relatively less COPD patients were observed among PTLD patients (10% vs. 34%, respectively, p=0. 28). Median time from transplantation to PTLD diagnosis was 41 (range 3–128) months, being among the longest to be reported in the literature among lung transplant recipients. Three patients developed early PTLD in our cohort, all were pre-transplant EBV seronegative and all were asymptomatic, diagnosed during surveillance chest imaging. In contrast, the seven late-onset PTLD cases were all EBV seropositive prior to transplantation, and were diagnosed after presenting with various symptoms, mainly B symptoms (71%). Overall extra-nodal involvement at presentation was very common for both PTLD forms (90%). While early onset PTLD uniformly involved the transplanted lung, this was relatively rare in the late-PTLD (100% vs. 14%, p=0. 03). According to the WHO classification, all PTLD specimens were monoclonal, based on molecular or light chain immuno-histochemistry. Eight (80%) cases were CD20 positive B cell lymphomas. EBV staining in the specimens was positive in 7 patients, including the 3 early-onset PTLD cases. All patients were treated with reduction of immunosuppression (Table). Other treatment modalities were diverse, including combination chemotherapy (6 patients), rituximab (6 patients), surgery (1 patient) and antiviral treatment (2 patients). 8 (80%) patients attained complete remission. With a median follow-up of 23 months, 6 patients died (3 from chronic rejection of the transplant, 1 from late chemotherapy toxicity, 1 from disease progression and 1 from unrelated cause). The median time from PTLD diagnosis to death was 19 months. Of the 8 patients attaining complete remission, only three patients are alive at the end of follow-up. Conclusion: Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD. This might be related to the high pre-transplant sero-prevalence to EBV in our cohort (96. 3%), as late-onset PTLD has been reported to be less associated with EBV proliferation. The majority of PTLD patients in our cohort died of treatment-related causes rather than disease progression. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 55 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Archana Bhaskaran ◽  
Dima Kabbani ◽  
Lianne G. Singer ◽  
Taisa Prochnow ◽  
Alya Bhimji ◽  
...  

2013 ◽  
Vol 67 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Nina Singh ◽  
Jose F. Suarez ◽  
Robin Avery ◽  
Cornelia Lass-Flörl ◽  
Christian Geltner ◽  
...  

2010 ◽  
Vol 54 (8) ◽  
pp. 3451-3459 ◽  
Author(s):  
Thomas J. Walsh ◽  
Sylvain Goutelle ◽  
Roger W. Jelliffe ◽  
Jeffrey A. Golden ◽  
Emily A. Little ◽  
...  

ABSTRACT Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg of micafungin administered intravenously in 20 adult lung transplant recipients. Epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage performed 3, 5, 8, 18, or 24 h after initiation of infusion. Micafungin concentrations in plasma, ELF, and ACs were determined using high-pressure liquid chromatography. Noncompartmental methods, population analysis, and multiple-dose simulations were used to calculate PKPD parameters. C max in plasma, ELF, and ACs was 4.93, 1.38, and 17.41 μg/ml, respectively. The elimination half-life in plasma was 12.1 h. Elevated concentrations in ELF and ACs were sustained during the 24-h sampling period, indicating prolonged compartmental half-lives. The mean micafungin concentration exceeded the MIC90 of A spergillus fumigatus (0.0156 μg/ml) in plasma (total and free), ELF, and ACs throughout the dosing interval. The area under the time-concentration curve from 0 to 24 h (AUC0-24)/MIC90 ratios in plasma, ELF, and ACs were 5,077, 923.1, and 13,340, respectively. Multiple-dose simulations demonstrated that ELF and AC concentrations of micafungin would continue to increase during 14 days of administration. We conclude that a single 150-mg intravenous dose of micafungin resulted in plasma, ELF, and AC concentrations that exceeded the MIC90 of A. fumigatus for 24 h and that these concentrations would continue to increase during 14 days of administration, supporting its potential activity for prevention and early treatment of pulmonary aspergillosis.


Sign in / Sign up

Export Citation Format

Share Document