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

• Published in: Bone marrow transplantation (Basingstoke) 2019-08, Vol.54 (Suppl 2), p.743-748
• Main Authors: Oevermann, Lena, Schulte, Johannes H., Hundsdörfer, Patrick, Hakimeh, Dani, Kogel, Friederike, Lang, Peter, Corbacioglu, Selim, Eggert, Angelika, Sodani, Pietro
• Format: Article
• Language: English
• Subjects: Activation; Adolescent; Azathioprine; Bone marrow; Busulfan; CD19 antigen; Cell Biology; Children; Cyclophosphamide; Depletion; Female; Fludarabine; Graft rejection; Graft-versus-host reaction; Grafting; Grafts; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Hemoglobinopathies; Hemoglobinopathy; Histocompatibility antigen HLA; Humans; Hydroxyurea; Immune reconstitution; Internal Medicine; Male; Medicine; Medicine & Public Health; Optimization; Patients; Pediatric research; Pediatrics; Pilot Projects; Public Health; Review Article; Risk factors; Sickle cell disease; Stem cell transplantation; Stem Cells; Survival; T cell receptors; Thalassemia; Transplantation; Transplantation Conditioning - methods; Transplantation, Haploidentical - methods; Transplants & implants; Treosulfan; Young Adult
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-019-0598-x

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.