Lum, Su HanAlbert, Michael H.Gilbert, PatrickSirait, TiarlanAlgeri, MattiaMuratori, RafaellaFournier, BenjaminLaberko, AlexandraKarakükcü, MusaÜnal, EkremAyas, Mouhab F.Yadav, Satya PrakashFışgın, TunçElfeky, ReemFernandes, Juliana FolloniFaraci, MauraCole, TheresaSchulz, Ansgar S.Meisel, RolandZecca, MarcoIfversen, MarienneBiffi, AlessandraDiana, Jean-SebastienVallee, Tanja C.Giardino, StefanoErsoy, Gizem ZenginMoshous, DespinaGennery, Andrew R.Balashov, DmitryBonfim Carmem M. S.Locatelli, FrancoLankester, Arjan C.Neven, BenedicteSlatter, Mary A.2024-05-062024-05-062024Lum, S. H., Albert, M. H., Gilbert, P., Sirait, T., Algeri, M., Muratori, R., Fournier, B., Laberko, A., Karakükcü, M., Ünal, E., Ayas, M. F., Yadav, S. P., Fışgın, T., Elfeky, R., Fernandes, J. F., Faraci, M., Cole, T., Schulz, A. S., Meisel, R., Zecca, M., Ifversen, M., Biffi, A., Diana, J.-S., Vallee, T. C., Giardino, S., Ersoy, G. Z., Moshous, D., Gennery, A. R., Balashov, D., Bonfim, C. M. S., Locatelli, F., Lankester, A. C., Neven, B., Slatter, M. A. (2024). Outcomes of HLA-mismatched HSCT with TCRαβ/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity. Blood, 144(5), 565-580. 10.1182/blood.20240240380006-49711528-0020https://hdl.handle.net/20.500.12939/4681HLA-mismatched transplants with either in vitro depletion of CD3+TCRαβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using post-transplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEI). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEI undergoing first transplant between 2010-2019 from an HLA-mismatched donor using TCRαβ (n=167) or PTCY (n=139). Median age at HSCT was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84%) after TCRαβ and 66% (57-74%) after PTCY (p=0.013). Pre-HSCT morbidity score (hazard ratio (HR) 2.27, 1.07-4.80, p=0.032) and non-Busulfan/Treosulfan conditioning (HR 3.12, 1.98-4.92, p<0.001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50-66%) after TCRαβ and 57% (48-66%) after PTCY (p=0.804). Cumulative incidence of severe acute GvHD was higher after PTCY (15%, 9-21%) than TCRαβ (6%, 2-9%, p=0.007), with no difference in chronic GvHD (PTCY, 11%, 6-17%; TCRαβ, 7%, 3-11%, p=0.173). The 3-year GvHD-free EFS was 53% (44-61%) after TCRαβ and 41% (32-50%) after PTCY (p=0.080). PTCY had significantly higher rates of veno-occlusive disease (14.4% versus TCRαβ 4.9%, p=0.009), acute kidney injury (12.7% versus 4.6%, p=0.032) and pulmonary complications (38.2% versus 24.1%, p=0.017). Adenoviraemia (18.3% versus PTCY 8.0%, p=0.015), primary graft failure (10%, versus 5%, p=0.048), and second HSCT (17.4% versus 7.9%, p=0.023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in IEI patients, although characterized by different advantages and outcomes.eninfo:eu-repo/semantics/closedAccessHLAInborn errors of immunity (IEI)Article1445565580386696312-s2.0-85196417938Q1WOS:001293213800001Q1