Slow Progression of Juvenile Metachromatic Leukodystrophy 6 Years After Bone Marrow Transplantation

Kapaun, Petra; Dittmann, Ralf W.; Granitzny, Barbara; Eickhoff, W.; Wulbrand, Henning; Neumaier-Probst, Eva; Zander, Axel R.; Kohlschuetter, A.

doi:10.1177/088307389901400402

Cited by 40 publications

(19 citation statements)

References 31 publications

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“…The time between the transplantation and the arrest of progression was individual, but it was within 12-24 months, an observation that concurs with other published material. 9,25,26 One of our patients developed mixed chimerism, but the available donor-derived cells provided enough enzyme to normalize the peripheral levels of ARSA. This finding is concurrent with the experience of HSCT for Gaucher's disease, where a stable mixed chimerism is sufficient for an excellent clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Solders

Martin

Andersson

et al. 2014

Bone Marrow Transplant

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In metachromatic leukodystrophy (MLD), the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) leads to demyelination in the central and peripheral nervous system and ultimately to death. Allogeneic hematopoietic SCT (HSCT) is currently the only treatment for adult and late-onset juvenile MLD, although it is still in question because of insufficient follow-up. We wanted to determine whether HSCT could halt the progression of adult and late-onset juvenile MLD. Four treated unrelated patients and three untreated siblings were included in the study, and followed regularly for up to 18 years after transplantation. The patients were assessed from clinical examination, ARSA enzyme levels, magnetic resonance imaging of the brain and neuropsychological and neurophysiological tests. In the treated patients, ARSA levels were normal up to 18 years after transplantation. The parameters evaluated stabilized and remained stable after a latency period of 12-24 months. Two patients live normal lives, partially in a protected environment. The other two patients stabilized at a low cognitive and functional level. One of the controls is demented, one is in a vegetative state and one died. We conclude that, in comparison with their untreated siblings, HSCT halted the progression of the disease in our treated patients.

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Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Solders

Martin

Andersson

et al. 2014

Bone Marrow Transplant

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“…27 Stable MRI findings, as visually analyzed, were also reported in a juvenile MLD patients who got HSCT at age 16, two years after first symptoms, and was followed up for 13 years. 28,29 In conclusion, HSCT early in the disease course can lead to a stabilization of juvenile MLD with a course clearly different from the natural history. We consider a crucial aspect in our patient was that HSCT was done early enough before the loss of walking could be anticipated according to the natural-history data, as this stage typically initiates rapid deterioration.…”

Section: Discussionmentioning

confidence: 99%

Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort

Krägeloh‐Mann

Groeschel

Kehrer

et al. 2012

Bone Marrow Transplant

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Metachromatic leukodystrophy (MLD) is a rare inborn error of metabolism leading to severe neurological symptoms and early death. Hematopoietic SCT (HSCT) is considered a treatment option, but results are inconsistent and comparison with natural history is practically missing. We compare a girl with juvenile MLD 10 years after allogeneic HSCT not only with her untreated sister, but also with a large cohort of untreated patients. The girl received HSCT at the age of 5 years when first motor signs appeared. Over 10 years she was stable with respect to her clinical course and gained cognitive abilities. Magnetic resonance imaging (MRI) showed clear regression of white matter changes and magnetic resonance spectroscopy (MRS) demonstrated a reversal of the initial choline increase and N-acetyl-aspartate (NAA) decrease. Only axonal demyelinating neuropathy showed some progression. Her gross motor function and MRI-scores were clearly better compared with her sister and the cohort of untreated patients. Difference to her sister became apparent only 4 years after HSCT. We conclude that HSCT, early in the course of disease, can lead to stabilization of juvenile MLD with a course clearly different from the natural history. HSCT may prevent disease progression, if performed sufficient time before loss of walking, which typically initiates rapid deterioration.

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“…The reported course, following HSCT, in juvenile/ adult forms appears to be often comparable with the natural course of the expected disease, which is usually characterized by a slow progression of symptoms. [30][31][32][33][34][35] Despite full engraftment and normalcy of enzymatic activity, in these forms the only benefit might be an improved survival in selected cases, whereas failure to obtain an improved or stabilized quality of life appears common. 27,28,36 Recent clinical evidence obtained in patients affected by globoid cell leukodystrophy, an LSD related to MLD and consequent to the deficiency of the enzyme involved in the downstream reaction, following ARSA, in the catabolism of myelin lipids, indicate that cord blood transplantation may favorably alter the natural history of infantile forms by delaying onset and progression if performed in asymptomatic newborns at less than 4 weeks of age.…”

Section: Hematopoietic Cell Transplantationmentioning

confidence: 99%