Upfront memory T cell add-back with haploidentical TCRαβ-depleted graft in adults with haematological malignancies: a nationwide, multicentre, single-arm, prospective study.

In haploidentical hematopoietic cell transplantation (Haplo-HCT), in vivo or ex vivo T-cell depletion (TCD) can prevent graft-versus-host disease (GVHD) but increase risk of infection and relapse. We hypothesized that TCRαβ-depleted allograft together with upfront infusion with CD45RA-depleted memory T cells (αβTCD + TMDLI) may result in favourable GVHD-free and relapse-free survival (GRFS). Between January 2017 and July 2023, 145 adult patients with various haematological malignancies received αβTCD + TMDLI. All except 2 patients had robust engraftment at a median of 12 days for neutrophil and 11 days for platelet. The cumulative incidence (CI) of CMV, EBV, HHV6 or ADV infection was only 43% (n = 63) at day+120. CI of grade II-IV and III-IV acute GVHD at 180 days was 31% and 8% respectively. Chronic GVHD was seen in only 5 patients with a 2-year CI of 4%. CI of non-relapse mortality and relapse at 2 years were 17% and 22% respectively. At a median follow up of 28 months, 3-year overall (OS), event-free (EFS), and GRFS were 67%, 62%, and 59%, respectively. This was significantly improved over a propensity score-matched contemporary cohort (n = 53) who received PTCy as GVHD prophylaxis. This first multi-center study demonstrated the potential benefits of the αβTCD + TMDLI approach for Haplo-HCT.