Nine-Year Experience with Treatment of Early Donor Specific Anti-HLA Antibodies in Pediatric Lung Transplant Recipients

Background: Experience with treatment of early detected donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2 g/kg, then 0.5 g/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins G (IgGAM), combined in some cases with plasmapheresis (PE) or immunoabsorption (3 or 5 sessions) before IgGAM and a single dose of anti-CD20 antibody (Rituximab) after the first IgGAM infusion. Aim of this study was to present the 9-year results of the IgGAM-based therapy in pediatric lung recipients.

Method: Records of pediatric (<18 years old) patients transplanted at our institution between January 2013 and August 2022 were reviewed. Outcomes of patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA (control group) were compared using the product-limit method of Kaplan–Meier and the log-rank test. Median (IQR) follow-up amounted to 50 (24–83) months.

Results: During the study period, among the 86 lung-transplanted pediatric patients (median age, 13 years), 38 (44%) formed the IgGAM group and 46 (53%) formed the control group. One (1%) patient was treated only with PE and Rituximab and 1 (1%) patient was not treated at all. These two patients were excluded from analysis.

Among the 38 IgGAM patients, 19 (50%) showed only eDSA (possible subclinical antibody-mediated rejection, AMR). The remaining 19 (50%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Three (8%) patients showed preformed DSA. Median time to eDSA detection was 21 (14–29) days after transplantation. As of August 2022, treatment was completed in 37 (97%) patients (1 patient still under treatment). Under IgGAM treatment, eDSA cleared in 35 (94.5%) patients. The same eDSA recurred in four (11.4%) patients.

At 8 years, graft survival (%) was 76 versus 66 (p = 0.95) and freedom (%) from chronic lung allograft rejection (CLAD) was 75 versus 54 (p = 0.27), in IgGAM versus control patients, respectively.

Conclusion: After lung transplantation, an IgGAM-based treatment for eDSA yielded high eDSA clearance. IgGAM patients showed 8-year CLAD-free survival at least as good as control patients without eDSA.

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Artikel online veröffentlicht:
28. Januar 2023