Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy
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Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy. / Cabanillas Stanchi, Karin Melanie; Böhringer, Judith; Strölin, Manuel; Groeschel, Samuel; Lenglinger, Katrin; Treuner, Claudia; Kehrer, Christiane; Laugwitz, Lucia; Bevot, Andrea; Kaiser, Nadja; Schumm, Michael; Lang, Peter; Handgretinger, Rupert; Krägeloh-Mann, Ingeborg; Müller, Ingo; Döring, Michaela.
In: STEM CELLS DEV, Vol. 31, No. 7-8, 04.2022, p. 163-175.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy
AU - Cabanillas Stanchi, Karin Melanie
AU - Böhringer, Judith
AU - Strölin, Manuel
AU - Groeschel, Samuel
AU - Lenglinger, Katrin
AU - Treuner, Claudia
AU - Kehrer, Christiane
AU - Laugwitz, Lucia
AU - Bevot, Andrea
AU - Kaiser, Nadja
AU - Schumm, Michael
AU - Lang, Peter
AU - Handgretinger, Rupert
AU - Krägeloh-Mann, Ingeborg
AU - Müller, Ingo
AU - Döring, Michaela
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Child
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Humans
KW - Leukodystrophy, Metachromatic/etiology
KW - Mesenchymal Stem Cell Transplantation/adverse effects
KW - Mesenchymal Stem Cells/physiology
KW - Prospective Studies
KW - Retrospective Studies
U2 - 10.1089/scd.2021.0352
DO - 10.1089/scd.2021.0352
M3 - SCORING: Journal article
C2 - 35323019
VL - 31
SP - 163
EP - 175
JO - STEM CELLS DEV
JF - STEM CELLS DEV
SN - 1547-3287
IS - 7-8
ER -
