Ten year follow-up of lung transplantations using initially rejected donor lungs after reconditioning using ex vivo lung perfusion

Abstract

Background In 2006 and 2007 we performed double lung transplantation with marginal donor lungs assessed and reconditioned by Ex Vivo Lung Perfusion (EVLP), using a technique developed by Professor Stig Steen. Here we present a 10-year follow-up comparing the outcomes of lung transplantations performed at our clinic using EVLP lungs vs. conventional lungs. Method Between 2006 and 2007, 21 patients (6 EVLP, 15 conventional) underwent double lung transplantation (LTx) with follow-up on May 2017 at Lund University Hospital, Sweden. Pulmonary function was measured at 3/6/12 months, and annually thereafter for a period of 10 years in addition to survival and freedom from chronic lung allograft dysfunction (CLAD) being analyzed. Results Regarding Forced Expiratory Volume in 1 s (FEV1) and 6MWT at 3, 6, and 12 months and annually thereafter, no difference in median FEV1 nor 6MWT was found for EVLP-LTx vs. conventional-LTx ( p > 0.05). No difference was shown in post-operative survival between EVLP-LTx vs. conventional LTx for patients with an overall survival up to 10-years (p > 0.05). The same pattern was shown in sub analyses for patients with a limited survival up to 1 and 5 years (p > 0.05). Conclusion No superiority was found in conventional-LTx over EVLP-LTx, neither in long-term survival nor pulmonary function. No difference in CLAD-free survival was seen between the two groups. We believe that EVLP is a safe and effective method to use in LTx, greatly increasing the donor pool by improving marginal lungs and providing an objective assessment of the viability of marginal donor lungs.

Ex-vivo lung perfusion versus standard protocol lung transplantation—mid-term survival and meta-analysis

“…In all, 13 studies were included for analysis (PRISMA diagram provided in Figure S1) (4,5,8,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). One randomized controlled trial (RCT) was included (27), while four studies were prospective, non-randomized trials (18,(20)(21)(22), six were retrospective series (4,5,8,23,25,26), and two were series with their design not fully described (19,24). One study was rated as standard quality, four as moderate quality, and eight as high quality ( Table S2).…”

“…While not detailed across all studies, the majority of all grafts were from braindead donors (DBD, 88.0%; 95% CI: 80. 4 Table 2 and per-study data in Table S4.…”

“…While lung transplantation (LTx) for patients with endstage pulmonary disease can be a life-saving measure, the scarcity of suitable donor lungs results in up to 30% of these patients dying while on the waiting list (1,2). Obtaining donor organs for LTx is particularly problematic, with donors of at least one other solid organ only having suitable lungs in 15-30% of cases according to current assessment criteria (3)(4)(5). End-of-life care, be it in the intensive care unit or otherwise, often results in damage to potential grafts and even under optimal donor circumstances, brain death still has the deleterious effect of causing neurogenic edema and a cytokine storm-induced inflammatory response (6).…”

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation

“…Further studies are necessary to determine whether these proposed benefits are translated into the clinic and such a trial is currently underway. There are also additional uses that may be further explored including the possibility of organ reconditioning during perfusion, which has been postulated to occur in other systems (2,24,25). The device may also be utilized as a platform for delivery of therapeutic agents, which could be added for the duration of storage but flushed out from the vasculature prior to transplantation if necessary.…”

Developments in lung transplantation over the past decade

“…With outcomes after EVLP, including long-term outcomes, that seem noninferior compared with normal cold storage LTx and high conversion rate to clinical LTx of previously discarded donor lungs, EVLP substantially expands the donor pool in LTx and has become standard of care in many centres over recent years and shows promise for future innovation [120,121]. Nevertheless, at this point, it still remains unclear in which settings and subgroups of marginal donors EVLP has most value.…”