Lung Allograft Rejection Gene Expression Observational (LARGO) Study

• Rejection episodes of at least moderate histologic grade which resulted in treatment of the patient with additional corticosteroids, anti-T cell antibodies, or total lymphoid irradiation. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Obliterative Bronchiolitis diagnosed pathologically by biopsy or by a progressive decline in pulmonary function tests consistent with a diagnosis of Bronchiolitis Obliterans Syndrome (BOS). [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Allograft function as determined via pulmonary function tests. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• The absence of histologic rejection and normal or unchanged allograft function. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Infections other than CMV, e.g. bacterial, other viral, and fungal infections. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]

• Rejection of mild to moderate histologic severity prompting augmentation of the patient's chronic immunosuppressive regimen. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Allograft dysfunction during the study period. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Rejection of mild to moderate severity with allograft dysfunction prompting plasmapheresis or a diagnosis of "humoral" rejection. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Lymphoproliferative disorder (aka post-transplant lymphoma). [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• Graft Failure or Retransplantation. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
• All cause mortality. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]

The objective of the LARGO Study protocol is to collect peripheral blood samples, select associated lung biopsy pathology slides, and clinical data from lung transplant recipients to perform molecular analyses in association with the study endpoints. The primary objective is to use gene expression profiling of peripheral blood mononuclear cells to differentiate between the absence and presence of acute cellular rejection. The secondary objectives are to use other genomic and proteomic technologies to analyze RNA and protein in blood samples in relation to related clinical conditions. The overall goal is to apply novel molecular insights in the development of non-invasive molecular diagnostic tests for lung transplantation.

LARGO is a prospective, multi-center, international observational study with participating centers in the United States, Canada and Europe. The target enrollment for study completion is 2,100 subjects.

At each study visit, blood specimens are collected from subjects, processed and stored in the sample archive, with corresponding patient information entered into the clinical database. The analysis plan for each study objective includes a defined sample selection protocol that stipulates the inclusion and exclusion criteria for both patients and samples, and also the required number of blood specimens for the molecular analyses to achieve statistical significance.

The diagnosis and treatment of acute cellular rejection remains a clinical management priority that is currently based on transbronchial biopsy. Gene expression profiling is a technology based on molecular biology that measures changes in the RNA levels of different genes expressed by circulating mononuclear cells in the peripheral blood. A key goal of the project is to use gene expression profiling to differentiate between the absence and presence of lung allograft acute cellular rejection, with the aim of using this novel information to develop a non-invasive diagnostic testing alternative.

Lung and heart-lung transplant recipients who will undergo transbronchial biopsy.

• Graft Rejection
• Lung Disease

Inclusion Criteria:

• Lung and heart-lung transplant recipients who consent to participate and have transbronchial biopsy at the enrolling center during the study period

Exclusion Criteria:

• None