TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia

We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated ( n =20) and haploidentical donors ( n =13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10 6 /kg of CD34+ and 20 × 10 3 /kg of αβ-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40–204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2–3 was 39 (26–60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18–50)%. Transplant-related mortality is 10(4–26)%. Event-free survival (EFS) is 60(43–76)% and overall survival (OS) is 67(50–84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48–84)% and OS−72(53–90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML