Access to Lung Transplantation for Candidates with Lung Fibrosis: «Anti-HLA Antibodies Also Matter». Usefulness of a Perioperative Desensitization Protocol in Sensitized Candidates.

Pre-formed donor-specific antibodies (DSA) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. This limitation to lung-graft allocation might be life-threatening, notably in patient with fibrosis on wait list. A virtual crossmatch (CXM)-based strategy for perioperative desensitization has been used for immunized LTx candidates in a cohort of 321 patients at Foch hospital (2012-2017 period).We analyzed the impact of this desensitization protocol on the access to LTx in candidates with fibrosis with pre-formed DSAs. Among LTx candidates with fibrosis, the access to LTx were compared between 3 groups: Group 1: Candidates with high pre-formed DSA (1000<MFI<5000) and who underwent desensitization protocol (n=7); Group 2: candidates with low levels pre-formed DSA (MFI<1000) (n=7), without desensitization; Group 3: candidates without preformed DSA (n=26). Perioperative desensitization included plasma exchange (PE), rituximab, IVIg, combined with high-dose mycophenolate mofetil (3g/day). Pre-formed DSAs at MFI >5000 were considered unauthorized for the desensitization protocol owing to the reported risk of positive real CXM. Among n=40 LTx candidates with fibrosis during this period, 85% had pre-formed DSA (Single-Ag Luminex assay). Mean calculated panel reactive antibodies (cPRA) was 39% at listing (taking into account all anti-HLA antibodies >500 MFI), and lowered to 6% with a desensitization strategy taking into account only anti-HLA antibodies >5000 (p<0.0001). Mean time on waiting list was 36 days, similar between the 3 groups (p=0.2). In Group 1, a significant decrease of immunodominant pre-formed DSA (class I/II) was observed at 6 months vs day 0 (p<0.001). Survival of the n=40 patients at 1 and 5 years post-LTx was 77% and 64%, respectively, and freedom from CLAD at 1 and 5 years were 96% and 75%, respectively, without significant difference between the 3 groups. A desensitization protocol allowed a satisfactory access to LTx for sensitized LTx candidates with fibrosis, with a post-LTx outcome similar to that of candidates with low-level or no pre-formed DSA. [ABSTRACT FROM AUTHOR]