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

Feb 13, 2023

Experts: M S Massei,I Capolsini,E Mastrodicasa,K Perruccio,F Arcioni,C Cerri,G Gurdo,S Sciabolacci,F Falzetti,T Zei,R Iacucci Ostini,M Brogna,B M Panizza,S Saldi,M Merluzzi,R Tognellini,M Marchesi,O Minelli,C Aristei,A Velardi,A Pierini,L Ruggeri,M F Martelli,A Carotti,M Caniglia

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 CD4CD25 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/Kg), Tregs (2 × 10/Kg) and Tcons (0.5-1 × 10/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.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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ABOUT THE EXPERTS

M S Massei,I Capolsini,E Mastrodicasa,K Perruccio,F Arcioni,C Cerri,G Gurdo,S Sciabolacci,F Falzetti,T Zei,R Iacucci Ostini,M Brogna,B M Panizza,S Saldi,M Merluzzi,R Tognellini,M Marchesi,O Minelli,C Aristei,A Velardi,A Pierini,L Ruggeri,M F Martelli,A Carotti,M Caniglia

M S Massei

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy. msperanza.massei@ospedale.perugia.it.

I Capolsini

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

E Mastrodicasa

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

K Perruccio

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

F Arcioni

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

C Cerri

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

G Gurdo

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

S Sciabolacci

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

F Falzetti

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

T Zei

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

R Iacucci Ostini

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

M Brogna

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

B M Panizza

Radiation Oncology Section, Santa Maria della Misericordia Hospital, Perugia, Italy.

S Saldi

Radiation Oncology Section, Santa Maria della Misericordia Hospital, Perugia, Italy.

M Merluzzi

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

R Tognellini

Immunohaematology, Transfusion Service and Apheresis, Santa Maria della Misericordia Hospital, Perugia, Italy.

M Marchesi

Immunohaematology, Transfusion Service and Apheresis, Santa Maria della Misericordia Hospital, Perugia, Italy.

O Minelli

Immunohaematology, Transfusion Service and Apheresis, Santa Maria della Misericordia Hospital, Perugia, Italy.

C Aristei

Radiation Oncology Section, Santa Maria della Misericordia Hospital, Perugia, Italy.

Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.

A Velardi

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

A Pierini

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

L Ruggeri

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

M F Martelli

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

A Carotti

Division of Hematology and Clinical Immunology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

M Caniglia

Pediatric Oncology-Hematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.