Improved GVHD-free and relapse-free survival after ex vivo αβTCR and CD19 depleted allogeneic HSCT compared to T cell replete HSCT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) aims to cure patients without inducing severe graft-versus-host disease (GVHD) or relapse. In prospective studies of mostly pediatric patients with haploidentical donors, ex vivo αβTCR/CD19 depletion has shown to have low incidences of GVHD, but data for adults with matched related (MRD) or unrelated donors (MUD) remain limited. We analyzed the outcomes of recipients who received a myeloablative regimen plus ATG, followed by an αβTCR/CD19-depleted allograft (cohort D+ATG (n = 122)), and compared outcomes to T cell-replete cohorts (cohort R (N = 60)); without ATG; R+ATG = with ATG (N = 129) in a single-center retrospective analysis. In D+ATG, the incidence of aGVHD grade III-IV was 7%, compared to 13% in R and 16% in R+ATG (p = 0.09). Extensive cGVHD was reduced from 23% in R and 10% in R+ATG to 2% in D+ATG (p < 0.001). The reduced incidence of cGVHD led to a superior GVHD-relapse-free survival (GRFS) of 56.7% in D+ATG versus 36.7% in R and 42.8% in R+ATG (p = 0.03) at 2 years. In conclusion, the combination of myeloablative conditioning, ATG, and ex vivo αβTCR/CD19 depletion appears to be a promising approach to enhance GRFS in adult patients up to 75 years of age undergoing allo-HSCT.