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 ]
  

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.