Association Between Cyclosporine Concentrations at 2 Hours Post-dose and Clinical Outcomes in De Novo Lung Transplant Recipients

2005 ◽  
Vol 24 (12) ◽  
pp. 2120-2128 ◽  
Author(s):  
Fatemeh Akhlaghi ◽  
Liliana Gonzalez ◽  
Andrew K. Trull
Keyword(s):  
Clinical Outcomes ◽  
Lung Transplant ◽  
De Novo ◽  
Transplant Recipients ◽  
Post Dose ◽  
Lung Transplant Recipients

scholarly journals Outcome of Extracorporeal Photopheresis as an Add-On Therapy for Antibody-Mediated Rejection in Lung Transplant Recipients

2020 ◽  
Vol 47 (3) ◽  
pp. 205-213
Author(s):  
Alberto Benazzo ◽  
Nina Worel ◽  
Stefan Schwarz ◽  
Ulrike Just ◽  
Anna Nechay ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Lung Transplant ◽  
De Novo ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Extracorporeal Photopheresis ◽  
Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Lung Transplant Recipients

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

Depression, Immunosuppressant Levels, and Clinical Outcomes in Postlung Transplant Recipients

2020 ◽  
Vol 55 (6) ◽  
pp. 421-436 ◽  
Author(s):  
Michael C Chu ◽  
Patrick J Smith ◽  
John M Reynolds ◽  
Scott M Palmer ◽  
Laurie D Snyder ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Lung Transplant ◽  
Epidemiological Studies ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Consecutive Series ◽  
Transplant Recipients ◽  
Increased Risk ◽  
Coefficient Of Variability ◽  
Lung Transplant Recipients

Objective Posttransplant depression has been linked to increased risk for adverse outcomes in lung transplant patients. Maintaining target serum immunosuppressant levels is also essential for optimal lung transplant clinical outcome and may be a crucial predictor of outcomes. Because depression could affect medication nonadherence, resulting in out-of-range immunosuppressant levels, we examined the relationship between posttransplant depression, immunosuppressant medication trough level variability, indexed by out-of-range values on clinical outcomes and coefficient of variability, and clinical outcomes. Method A consecutive series of 236 lung transplant recipients completed the Center for Epidemiological Studies-Depression two-month posttransplant. Immunosuppressant trough levels (i.e., tacrolimus or cyclosporine) within the range of individualized immunosuppressant targets were obtained at three-, six-, nine-month follow-up clinic visits. Clinical outcomes including hospitalizations and mortality were obtained from medical records. Results Fourteen percent of patients were classified as depressed (Center for Epidemiological Studies-Depression ≥16), 144 (61%) of patients had at least 25% out-of-range immunosuppressant values, and the average coefficient of variability was 36%. Over a median of 2.6 years (interquartile range = 1.2), 32 participants died (14%) and 144 (61%) had at least one unplanned, transplant-related hospitalization. Both depression (hazard ratio = 1.45 (1.19, 1.76), p < . 01) and immunosuppressant variation (immunosuppressant out-of-range: hazard ratio = 1.41 (1.10, 1.81), p < .01) independently predicted more frequent hospitalizations and higher mortality. Conclusions Early posttransplant depression was associated with significantly worse clinical outcomes. While immunosuppressant level variability is also related to adverse outcomes, such variability does not account for increased risk observed with depression.

scholarly journals Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Danielle P. Porter ◽  
Ying Guo ◽  
Jason Perry ◽  
David L. Gossage ◽  
Timothy R. Watkins ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Respiratory Syncytial Virus ◽  
Clinical Outcomes ◽  
Lung Transplant ◽  
Fusion Inhibitor ◽  
Transplant Recipients ◽  
Genotypic Resistance ◽  
Resistance Development ◽  
Syncytial Virus ◽  
Lung Transplant Recipients

ABSTRACT This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults. Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported. Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but they had similar clinical outcomes. Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with genotypic resistance development had decreased virologic responses compared to those without genotypic resistance but had comparable clinical outcomes.

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