Preformed Donor-Specific Antibodies in Lung Transplantation: Eight-Year Experience with Perioperative Desensitization Using IgA- and IgM-Enriched Human Immunoglobulins

Background: Pretransplant sensitization to human leukocyte antigens (HLA) increases the recipient waiting list time and mortality in lung transplantation. Instead of awaiting crossmatch-negative donors, since 2013, recipients with preformed anti-HLA donor specific antibodies (pfDSA) have been managed peri-transplant at our institution with a combination of repeated IgA- and IgM-enriched intravenous immunoglobulin infusions (IgGAM, first infusion: 2 g/kg, then 0.5 g/kg every 4 weeks thereafter to a maximum of 6 months), preceded by repeated plasmapheresis (PE), and a single dose of anti-CD20 antibody (375 mg/m², Rituximab) after the first IgGAM infusion. This study presents the 8-year results of this protocol in patients transplanted with pfDSA.

Method: Records of patients transplanted at our institution between February 2013 and August 2021 were reviewed. Outcomes were compared between patients with pfDSA (pfDSA group) and those without any DSA (control group). Patients without pfDSA who developed de-novo DSA only post transplantation (n = 220) were excluded from the study. Median follow-up was 47 (20–72) months.

Results: Of the 987 transplanted patients, 49 (5%) patients exhibited pfDSA and 718 (73%) did not develop any DSA (control group). Among these 49 patients, 34 (69%) patients possessed pfDSA against class II HLA antigens, 13 (27%) patients against class I antigens, and 2 (4%) patients against both classes. Ten (20%) patients showed a positive retrospective CDC crossmatch and 19 (39%) patients developed additional de-novo DSA after transplantation. Thirty-eight (78%) patients were treated with PE and 41 (84%) patients with Rituximab. At follow-up end, treatment was completed in 42 (86%) patients (still on treatment, n = 1; in-hospital deaths, n = 2; treatment interrupted earlier as intended by protocol, n = 4). In these 42 patients, IgGAM treatment cleared eDSA in 30 (71%) patients, with 3 (10%) patients showing eDSA recurrence.

In pfDSA versus control patients and at 5-year follow-up, respectively, graft survival (%) was 85 versus 76 (p = 0.39) and freedom from chronic lung allograft dysfunction (%, CLAD) was 76 versus 72 (p = 0.93).

Conclusion: In lung transplantation, a treatment protocol based on IgGAM allowed transplanting patients with preformed DSA with good 5-year graft survival similar to control patients.

Die Autoren geben an, dass kein Interessenkonflikt besteht.

Publikationsverlauf

Artikel online veröffentlicht:
03. Februar 2022