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  • Review Article
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HLA-haploidentical hematopoietic stem cell transplantation in pediatric patients with hemoglobinopathies: current practice and new approaches

Abstract

We review current approaches in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for pediatric patients with hemoglobinopathies with a focus on recent developments using TCRα/β+/CD19+ depleted grafts in patients with β-thalassemia major (TM) or sickle cell disease (SCD) in two European transplant units. Eleven TM and three SCD patients (Roma cohort) received a preparative regimen consisting of busulfan/thiotepa/cyclophosphamide/ATG preceded by fludarabine/hydroxyurea/azathioprine. The preparative regimen for 5 SCD patients included treosulfan/thiotepa/fludarabine/ATG (Berlin pilot cohort). All grafts were PBSC engineered by TCR-α/β+/CD19+ depletion. In both cohorts, rates for graft failure, treatment related mortality (TRM) and GvHD were encouraging. Overall survival (OS) and disease-free survival (DFS) in the Roma cohort were 84 and 69%, respectively, while OS and DFS are 100% in the Berlin cohort. Immune reconstitution was satisfactory. Although asymptomatic viral reactivation was common, no severe viral infection occured. These data confirm that TCR-α/β+/CD19+ depletion is a well-suited haplo-HSCT strategy for children with hemoglobinopathies. We discuss the results in the context of additional optimization strategies and introduce our concepts for multicenter trial protocols in Germany.

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Acknowledgements

The authors thank the former Scientific Director of the IME, who pioneered haplo-HSCT for thalassemia.

Funding

Publication of this supplement was sponsored by Gilead Sciences Europe Ltd, Cell Source, Inc., The Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science, Kiadis Pharma, Miltenyi Biotec, Celgene, Centro Servizi Congressuali, Almog Diagnostic. LO, JS, PH and AE have been supported by grants of the Berlin Institute of Health.

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Correspondence to Pietro Sodani.

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DH received consulting fees and lecture fees from Novartis. The remaining authors decalred that they have no conflict of interest.

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Oevermann, L., Schulte, J.H., Hundsdörfer, P. et al. HLA-haploidentical hematopoietic stem cell transplantation in pediatric patients with hemoglobinopathies: current practice and new approaches. Bone Marrow Transplant 54 (Suppl 2), 743–748 (2019). https://doi.org/10.1038/s41409-019-0598-x

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