scholarly journals Long-Term Neurodevelopmental Outcomes of Hematopoietic Stem Cell Transplantation for Late-Infantile Krabbe Disease

Blood ◽  
2020 ◽  
Author(s):  
Isabel C Yoon ◽  
Nicholas A Bascou ◽  
Michele D Poe ◽  
Paul Szabolcs ◽  
Maria L Escolar
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Symptom Onset ◽  
Disease Onset ◽  
Krabbe Disease ◽  
Hematopoietic Stem ◽  
Prospective Longitudinal

Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in galactocerebrosidase. The only effective treatment is hematopoietic stem cell transplantation (HSCT). Approximately 85% of Krabbe cases are the infantile subtypes, among which ~20% are late-infantile. Prior studies demonstrated that HSCT is effective for early-infantile patients (0 - 6 months of age) transplanted while asymptomatic, compared to those transplanted while symptomatic. However, no studies evaluated the efficacy of HSCT for late-infantile patients (6 - 36 months). In this prospective, longitudinal study, patients were evaluated at a single site following a standardized protocol. Survival analysis was performed using the Kaplan-Meier method. Differences between groups were estimated using Mixed Regression models to account for within person repeated measures. Nineteen late-infantile patients underwent HSCT (1997 - 2020). Compared to untreated patients, transplanted patients had a longer survival probability and improved cognitive and language function. Gross and fine motor development were most affected with variable results. Asymptomatic patients benefitted the most from transplantation with normal to near-normal development in all domains and some gross motor delays. Among symptomatic patients, those with disease onset > 12 months of age had better cognitive outcomes than untreated patients. Those with disease onset £ 12 months were comparable to untreated patients. We found that HSCT prolongs the lifespan and improves the functional abilities of late-infantile Krabbe patients, particularly for those transplanted before symptom onset. In addition, our findings support prior literature that reclassifies late-infantile Krabbe disease to be symptom onset 12 to 36 months of age.

Hematopoietic Stem Cell Transplantation for Late-Onset Krabbe Disease

2015 ◽  
Vol 46 (S 01) ◽  
Author(s):  
A. Bley ◽  
U. Löbel ◽  
M. Nickel ◽  
A. Ohlenbusch ◽  
J. Denecke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Late Onset ◽  
Krabbe Disease ◽  
Hematopoietic Stem

scholarly journals Nine-year follow up after hematopoietic stem cell transplantation in five multiple sclerosis patients

2019 ◽  
Vol 77 (8) ◽  
pp. 531-535 ◽  
Author(s):  
Elizabeth R. Comini-Frota ◽  
Bruna C. C. Marques ◽  
Caio Torres ◽  
Karoline M. S. Cohen ◽  
Eduardo Carvalho Miranda
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Activity ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Onset ◽  
Hematopoietic Stem ◽  
Relapsing Remitting

ABSTRACT Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Its treatment has focused on inflammation control as early as possible to avoid disability. Autologous hematopoietic stem cell transplantation (AHSCT) has been used for treating MS since 1996, with recent decisive results regarding benefits in long-term efficacy. Five patients followed up at an MS center in Belo Horizonte, Brazil, who had relapsing-remitting MS with high disease activity, underwent AHSCT between 2009 and 2011. They were evaluated clinically, with magnetic resonance imaging, and by the EDSS every six months after transplantation, up to July 2018. The patients were four women and one man, with ages ranging from 25-50 years, and time since disease onset ranging from 4-17 years at the time of the procedure. Four patients improved, one patient was stabilized, and all patients were free of disease activity after 5-9 years. Through improving patient selection and decreasing the time from disease onset, AHSCT could stop epitope spreading and disease progression. Despite multiple other therapeutic choices being approved for relapsing-remitting MS, AHSCT continues to be a treatment to consider for aggressive MS disease.

scholarly journals β-Galactosylceramidase Deficiency Causes Bone Marrow Vascular Defects in an Animal Model of Krabbe Disease

2019 ◽  
Vol 21 (1) ◽  
pp. 251
Author(s):  
Mirella Belleri ◽  
Daniela Coltrini ◽  
Marco Righi ◽  
Cosetta Ravelli ◽  
Sara Taranto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Krabbe Disease ◽  
Microscopy Imaging ◽  
Hematopoietic Stem

Krabbe disease (KD) is an autosomal recessive sphingolipidosis caused by the deficiency of the lysosomal hydrolase β-galactosylceramidase (GALC). Oligodendroglia degeneration and demyelination of the nervous system lead to neurological dysfunctions which are usually lethal by two years of age. At present, the only clinical treatment with any proven efficacy is hematopoietic stem-cell transplantation, which is more effective when administered in the neonatal period to presymptomatic recipients. Bone marrow (BM) sinusoidal endothelial cells (SECs) play a pivotal role in stem cell engraftment and reconstitution of hematopoiesis. Previous observations had shown significant alterations of microvascular endothelial cells in the brain of KD patients and in Galc mutant twitcher mice, an authentic model of the disease. In the present study, we investigated the vascular component of the BM in the femurs of symptomatic homozygous twitcher mice at postnatal day P36. Histological, immunohistochemical, and two-photon microscopy imaging analyses revealed the presence of significant alterations of the diaphyseal BM vasculature, characterized by enlarged, discontinuous, and hemorrhagic SECs that express the endothelial marker vascular endothelial growth factor receptor-2 (VEGFR2) but lack platelet/endothelial cell adhesion molecule-1 (CD31) expression. In addition, computer-aided image analysis indicates that twitcher CD31−/VEGFR2+ SECs show a significant increase in lumen size and in the number and size of endothelial gaps compared to BM SECs of wild type littermates. These results suggest that morphofunctional defects in the BM vascular niche may contribute to the limited therapeutic efficacy of hematopoietic stem-cell transplantation in KD patients at symptomatic stages of the disease.

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