HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia.
M S MasseiI CapolsiniE MastrodicasaKatia PerruccioF ArcioniC CerriG GurdoS SciabolacciF FalzettiT ZeiR Iacucci OstiniM BrognaB M PanizzaS SaldiM MerluzziR TognelliniM MarchesiO MinelliC AristeiA VelardiA PieriniLoredana RuggeriM F MartelliA CarottiM CanigliaPublished in: Bone marrow transplantation (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 × 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.
Keyphrases
- acute myeloid leukemia
- end stage renal disease
- acute lymphoblastic leukemia
- allogeneic hematopoietic stem cell transplantation
- regulatory t cells
- newly diagnosed
- ejection fraction
- bone marrow
- prognostic factors
- peritoneal dialysis
- stem cells
- traumatic brain injury
- induced apoptosis
- patient reported outcomes
- risk factors
- radiation therapy
- adipose tissue
- cell therapy
- insulin resistance
- metabolic syndrome
- intensive care unit
- hepatitis b virus
- mesenchymal stem cells
- signaling pathway
- oxidative stress
- patient reported
- cardiovascular events
- endoplasmic reticulum stress
- cord blood
- acute respiratory distress syndrome