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.

INDIRECT RECOGNITION OF DONOR HLA CLASS I PEPTIDES IN LUNG TRANSPLANT RECIPIENTS WITH BRONCHIOLITIS OBLITERANS SYNDROME1

1999 ◽  
Vol 67 (8) ◽  
pp. 1094-1098 ◽  
Author(s):  
Krovvidi S.R. SivaSai ◽  
Michael A. Smith ◽  
Nancy J. Poindexter ◽  
Sudhir R. Sundaresan ◽  
Elbert P. Trulock ◽  
...  
Keyword(s):  
Bronchiolitis Obliterans ◽  
Lung Transplant ◽  
Hla Class I ◽  
Class I ◽  
Transplant Recipients ◽  
Lung Transplant Recipients

Antibody-Mediated Rejection Management Following Lung Transplantation

2021 ◽  
pp. 106002802110124
Author(s):  
Kristen Neuhaus ◽  
Benjamin Hohlfelder ◽  
Jessica Bollinger ◽  
Marcus Haug ◽  
Heather Torbic
Keyword(s):  
Lung Transplantation ◽  
Lung Transplant ◽  
Management Strategies ◽  
Organ Transplant ◽  
Outcome Analysis ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Patient Admissions ◽  
Lung Transplant Recipients

Background Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. Objective The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. Methods This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. Results A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. Conclusion and Relevance This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

scholarly journals Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation

2018 ◽  
Vol 29 (1) ◽  
pp. 18-25
Author(s):  
Alicia B. Lichvar ◽  
Christopher R. Ensor ◽  
Adriana Zeevi ◽  
Matthew R. Morrell ◽  
Joseph M. Pilewski ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Immunoglobulin G ◽  
Lung Transplant ◽  
Primary Outcome ◽  
Transplant Recipients ◽  
Chronic Lung Allograft Dysfunction ◽  
On Demand ◽  
Allograft Dysfunction ◽  
Group 2 ◽  
Lung Transplant Recipients

Background: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. Materials and Methods: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. Results: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). Conclusions: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

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