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

Abstract

Purpose Experience with treatment of early 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: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins (Pentaglobin, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aim of this study was to present the 5-year results of the IgGAM-based therapy in pediatric lung recipients. Methods Records of pediatric ( Results During the study period, among the 60 lung-transplanted pediatric patients (median age 13 years), 26 (43%) formed the IgGAM group and 33 (55%) the control group. One (2%) patient was treated only with PE and Rituximab and not considered in the study. Among the 26 IgGAM patients, 14 (54%) showed only eDSA (possible subclinical antibody-mediated rejection, AMR). The remaining 12 (46%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 23 (14, 64) days after transplantation. As of October 2018, treatment was completed in 23 (88%) patients. Under IgGAM treatment eDSA cleared in 22 (96%) patients. At follow-up, 5 (20%) IgGAM vs. 5 (15%) control patients developed hypogammaglobulinemia requiring substitution (p=0.73). No IgGAM vs. 3 (10%) control patients developed post-transplant lymphoproliferative disease (p=0.25). At 5 years, graft survival (%) was 76 vs. 84 (p=0.78); freedom (%) from chronic lung allograft rejection (CLAD) was 88 vs. 75 (p=0.54), and from infection requiring hospitalization 53 vs. 23 (p= 0.021), in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, an IgGAM-based treatment for eDSA yielded high eDSA clearance while decreasing the risk of severe infections. IgGAM patients showed 5-year CLAD-free survival at least as good as control patients without eDSA.