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Depletion of αβ T cells from the graft prevents graft-vs.-host disease (GVHD) and improves outcome of HSCT from haploidentical donors. In a randomized trial, we aimed to evaluate the safety and efficacy of low-dose memory (CD45RA-depleted) donor lymphocytes (mDLI) after HSCT with αβ T-cell depletion. A cohort of 149 children was enrolled, 76 were randomized to receive scheduled mDLI and 73 received standard care. Conditioning was based on either 12 Gy total body irradiation or treosulfan. Rabbit antithymocyte globulin was replaced by tocilizumab and abatacept. Primary end points were the incidence of acute GVHD grades II–IV and the incidence of cytomegalovirus (CMV) viremia. The incidence of grades II–IV aGVHD was 14% in the experimental arm and 12% in the control arm, p—0.8. The incidence of CMV viremia was 45% in the experimental arm and 55% in the control arm, p—0.4. Overall, in the total cohort 2-year NRM was 2%, cumulative incidence of relapse was 25%, event-free survival 71%, and overall survival 80%, without difference between the study arms. Memory DLI was associated with improved recovery of CMV-specific T-cell responses in a subcohort of CMV IgG seropositive recipients.

Hematopoietic stem cell transplantation (HSCT) is a curative option for children with high-risk acute lymphoblastic leukemia (ALL). This retrospective single-center study analyzed 236 pediatric ALL patients in complete remission who underwent allogeneic HSCT using ex-vivo T cell depletion between 2012 and 2021. The majority received haploidentical grafts ( n  = 202), while the remainder received matched unrelated donor (MUD) grafts ( n  = 34). At four years, event-free survival (EFS) and overall survival (OS) were 57% and 67%, respectively. Total body irradiation (TBI)-based conditioning was associated with significantly lower relapse rates and superior EFS compared to chemotherapy-based regimens. Non-relapse mortality (NRM) was low (9%), with no significant difference between donor types. Pre-transplant minimal residual disease (MRD) positivity and transplantation beyond first complete remission were independently associated with higher relapse and inferior survival. Chronic GVHD incidence was lower in patients receiving abatacept and tocilizumab instead of ATG. These findings confirm the safety and efficacy of ex-vivo T cell-depleted HSCT in pediatric ALL, with outcomes comparable between haploidentical and MUD donors. TBI-based conditioning and MRD negativity remain key prognostic factors for improved outcome.

The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts.A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire.In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.