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

Bone Marrow Transplant. 2019 Aug;54(Suppl 2):743-748. 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hemoglobinopathies
  • Humans
  • Male
  • Pilot Projects
  • Transplantation Conditioning / methods*
  • Transplantation, Haploidentical / methods*
  • Young Adult