Unrelated donor α/β T-cell and B-cell-depleted HSCT for the treatment of pediatric acute leukemia

Abstract

Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe GVHD. TCRαβ/CD19 depletion may reduce this risk, while maintaining graft-versus-leukemia. Outcome data with TCRαβ/CD19 depletion generally describes haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at two large pediatric transplantation centers between 10/2014 and 09/2019. All patients with acute leukemia had minimal residual disease testing and DP typing was available for 77%. All patients received myeloablative TBI- or busulfan-based conditioning with no post-transplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95%CI 52-81%) and leukemia-free survival was 64% (95%CI 48-76%), with no difference between lymphoid and myeloid malignancies (p=0.6297 and p=0.5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence 21%, 95%CI 11-34), and 8 patients (cumulative incidence 15%, 95%CI 6.7-26) experienced non-relapse mortality. Grade III-IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Non-permissive DP mismatch was associated with higher likelihood of acute GVHD (OR 16.50, 95%CI 1.67-163.42, p=0.0166), but not with the development of chronic GVHD. URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.