Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy.

Journal: Stem Cells And Development
Treatment Used: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Mesenchymal Stromal Cells (MSCs)
Number of Patients: 10
Published:
MediFind Summary

Summary: This analysis evaluated allogeneic hematopoietic stem cell transplantation (uses healthy blood stem cells from a donor to replace diseased or damaged bone marrow; HSCT) with mesenchymal stem cells (adult stem cells isolated from different sources that can differentiate into other types of cells; MSCs) in children with metachromatic leukodystrophy (inherited disorder characterized by the accumulation of fats called sulfatides in cells; MLD).

Conclusion: The application of mesenchymal stem cells (adult stem cells isolated from different sources that can differentiate into other types of cells) after allogeneic hematopoietic stem cell transplantation (uses healthy blood stem cells from a donor to replace diseased or damaged bone marrow) was safe and well tolerated in children with metachromatic leukodystrophy (inherited disorder characterized by the accumulation of fats called sulfatides in cells).

Abstract

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 × 106 MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol·10-6 and range 0.41-1.73 | MSCG: median 1.58 nmol·10-6 and range 0.44-2.6; P < 0.05), as well as significantly higher leukocyte (P < 0.05) and thrombocyte (P < 0.001) levels within 365 days of MSC application compared to CG patients. Statistically significant effects on acute GvHD, regeneration of immune cells, MRI changes, gross motor function, and clinical outcomes were not detected. In conclusion, the application of MSCs in pediatric MLD patients after allogeneic HSCT was safe and well tolerated. The two applications of 2 × 106/kg allogeneic MSCs were followed by improved engraftment and hematopoiesis within the first year after HSCT. Larger, prospective trials are necessary to evaluate the impact of MSC application on engraftment and hematopoietic recovery.

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