Impact of Portable Ex Vivo Lung Perfusion with the Organ Care System on Freedom from CLAD

Background: Severe primary graft dysfunction (PGD3) early after lung transplantation has been firmly linked to impaired survival and increased rates of chronic rejection (chronic lung allograft dysfunction, CLAD) previously. Innovative lung preservation methods are needed to reduce the incidence of PGD3 and thus later CLAD. The international, multicenter, prospective, randomized INSPIRE trial compared portable donor lung ex-vivo perfusion (EVLP) using the OCS lung device (OCS, Transmedics, Inc.) to cold storage (Control). The early rate of severe PGD was significantly reduced. Survival was not different from controls. Long term outcomes and rates of CLAD have not been reported before.

Methods: Bilateral transplantations with donors aged < 65 years and paO₂/FiO₂ ratios >300 mm Hg were included. Lungs in the OCS were perfused with OCS lung solution or low-potassium dextran solution augmented with packed red cells. All patients were followed up for 2 years posttransplantation. Longer follow up is available from those patients transplanted at Hannover Medical School.

Results: 141 OCS and 165 Control group patients were treated per-protocol. Of these, 38 and 47, respectively, were transplanted at Hannover Medical School, the largest of 21 enrolling sites. Incidence of PGD3 within 72 hours had been reported before and was 18% in the OCS arm versus 30% in the Control arm (p = 0.015). Six-months (OCS: 91% versus Control: 94%) and one-year survivals (OCS: 89% versus Control: 89%) were not significantly different. Freedom from CLAD was 98% in the OCS and 96% in the Control arm at 12 months and 88% (OCS) and 85% (Control) at 24 months. Beyond 24 months, data from the full study cohort is not yet available. In the subcohort of patients enrolled and transplanted in Hannover, however, constituting more than a quarter of the total trial population, further follow-up is on hand. At 12 months, in the Hannover cohort of INSPIRE patients, freedom from CLAD is 97% in the OCS and 96% in the Control arm. At 36 months, this is down to 78% (OCS, 24 patients at risk) and 68% (Control, 28 patients at risk).

Conclusion: The INSPIRE trial showed a significant reduction of PGD grade 3 in the OCS group, providing evidence supporting normothermic preservation with portable EVLP in routine lung transplantation. Follow up to 36 months reveals a strong trend toward higher freedom from chronic rejection (CLAD) in the OCS group.