T-replete HLA-matched Grafts vs T-depleted HLA-mismatched Grafts in Inborn Errors of Immunity

Abstract

Haematopoietic cell transplantation (HCT) has become standard of care for an increasing number of inborn errors of immunity (IEI). This is the first report to compare the transplant outcomes according to T-replete HLA-matched grafts using alemtuzumab (n=117) and T-depleted HLA-mismatched grafts using TCR αβ/CD19 depletion (n=47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, PBSC in 85 (73%) and CB in 7 (6%). TCR αβ/CD19 depletion was performed on PBSC from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year OS and EFS for the entire cohort were 85% (77-90%) and 79% (69-86%) respectively. Analysis by age at transplant revealed a comparable 3-year OS between T-replete grafts (88%, 76-94%) and T-depleted grafts (87%, 64-96%) in younger patients (<5 years of age at HCT). For older patients more than 5 years of age, the OS was significantly lower in T-depleted grafts (55%, 23-78%), compared to T-replete grafts (87%, 68-95%) (p=0.03). Grade III-IV aGvHD was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete CB and 2% of T-depleted PBSC (p=0.73). Higher incidence of viraemia (p<0.001) and delayed CD3 reconstitution (p=0.003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCR αβ and CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft.