HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia

by Selleckchem | Mar 07 2023

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4+CD25+ FoxP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4-21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 106/Kg), Tregs (2 × 106/Kg) and Tcons (0.5-1 × 106/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1-4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2-4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months-5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.

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The presented study describes a novel HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) strategy for high-risk acute leukemia in pediatric patients. The strategy involves adoptive immunotherapy with a combination of thymic-derived CD4+CD25+ FoxP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) in addition to a conditioning regimen including total body irradiation (TBI), thiotepa, fludarabine, and cyclophosphamide.

The study includes 20 pediatric patients (15 with acute lymphoblastic leukemia, and 5 with acute myeloid leukemia) with a median age of 14.5 years. The grafts contained a megadose of CD34+ cells, Tregs, and Tcons. All patients achieved sustained full-donor engraftment, and only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients), and five patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). Four patients with aGvHD resolved and are alive and disease-free, while one patient developed chronic GvHD (cGvHD).

The probability of Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS) was 60 ± 0.5% (95% CI: 2.1-4.2), and the probability of Cancer-Free, Relapse-Free Survival (CRFS) was 79 ± 0.9% (95% CI: 3.2-4.9). Sixteen out of 20 patients are alive and leukemia-free with a median follow-up of 2.1 years (range 0.5 months-5.1 years).

Overall, the study suggests that the haplo-HSCT strategy with adoptive immunotherapy using Tregs and Tcons is associated with promising outcomes in pediatric patients with high-risk acute leukemia who lack an HLA-matched donor. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm the results and establish the safety and efficacy of the approach.