ABSTRACT
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.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Child , Adolescent , Immunotherapy, Adoptive/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Leukemia, Myeloid, Acute/complications , Hematopoietic Stem Cells , Transplantation Conditioning/adverse effectsABSTRACT
We describe the case a 2-day-old female with congenital glioblastoma. Total resection was followed by adjuvant and high dose chemotherapy, as indicated by the current Italian infant protocol. The child is alive and well 18 months after diagnosis. A review of 67 selected congenital brain tumors showed the mortality rate was 82%. Even though the majority of patients had glioblastoma, only 5/67 had received adjuvant therapy. To ensure optimal outcomes, we recommend total or subtotal surgical resection, followed by adjuvant and high dose chemotherapy. Given the lack specific protocols for congenital brain tumors an international consensus seems to be needed, starting with congenital glioblastoma.
