HLA 单倍体相合造血干细胞移植联合调节性 T 细胞和常规 T 细胞过继免疫治疗用于极高危急性白血病儿科患者

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 × 10 6 /Kg), Tregs (2 × 10 6 /Kg) and Tcons (0. 5-1 × 10 6 /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.