Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients

Groeschel, Samuel; Kühl, Jörn‐Sven; Bley, Annette; Kehrer, Christiane; Weschke, Bernhard; Döring, Michaela; Böhringer, Judith; Schrum, Johanna; Santer, René; Kohlschütter, Alfried; Krägeloh‐Mann, Ingeborg; Müller, Ingo

doi:10.1001/jamaneurol.2016.2067

Cited by 111 publications

(164 citation statements)

References 32 publications

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“…New therapeutic approaches are currently under investigation 1, 15. There is an increasing body of evidence suggesting that successful therapy is related to early treatment, that is, presymptomatic and early symptomatic,16, 17, 18, 19 and to a slower disease progression, that is, treatments such as HSCT being more effective in the more slowly progressive juvenile form than in the rapidly progressive late‐infantile form 17, 18. Thus, one of the clinical challenges when to recommend HSCT in juvenile MLD is to judge on the dynamics of the disease course.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it seems important to investigate whether the demyelination load is a clinically relevant parameter, not only to describe, but also to predict disease progression in juvenile MLD. Especially, as HSCT was proven to be a beneficial treatment when done at an early stage of the disease before the phase of rapid progression 16, 17, 18, 19. It seems essential to find predictors of disease progression already early during disease course in order to be able to judge on the “window of opportunity,” for example, whether a treatment has enough time to become effective.…”

Section: Introductionmentioning

confidence: 99%

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Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy

Strölin

Krägeloh‐Mann

Kehrer

et al. 2017

Ann Clin Transl Neurol

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ObjectiveThe aim of this study was to investigate whether the extent and topography of cerebral demyelination correlates with and predicts disease progression in patients with juvenile metachromatic leukodystrophy (MLD).MethodsA total of 137 MRIs of 46 patients with juvenile MLD were analyzed. Demyelination load and brain volume were quantified using the previously developed Software “clusterize.” Clinical data were collected within the German Leukodystrophy Network and included full scale intelligence quotient (FSIQ) and gross motor function data. Voxel‐based lesion‐symptom mapping (VLSM) across the whole brain was performed to investigate the spatial relationship of cerebral demyelination with motor or cognitive function. The prognostic value of the demyelination load at disease onset was assessed to determine the severity of disease progression.ResultsThe demyelination load (corrected by the individual brain volume) correlated significantly with gross motor function (r = +0.55) and FSIQ (r = −0.55). Demyelination load at disease onset was associated with the severity of disease progression later on (P < 0.01). VLSM results associated frontal lobe demyelination with loss in FSIQ and more central region demyelination with decline of motor function. Especially progression of demyelination within the motor area was associated with severe disease progression.InterpretationWe were able to show for the first time in a large cohort of patients with juvenile MLD that the demyelination load correlates with motor and cognitive symptoms. Moreover, demyelination load at disease onset, especially the involvement of the central region, predicts severity of disease progression. Thus, demyelination load seems a functionally relevant MRI parameter.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy

Strölin

Krägeloh‐Mann

Kehrer

et al. 2017

Ann Clin Transl Neurol

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“…However, his diagnosis allowed the detection of patient MLD8b before disease onset. And indeed, two recent studies -a prospective cohort and case-control study -have raised evidence that HSCT is associated with a reasonable chance of disease stabilization if performed pre-symptomatically 10,16 . Patient MLD-9 came for HSCT evaluation one year after the beginning of cognitive losses.…”

Section: Discussionmentioning

confidence: 99%

“…Case reports suggested that HSCT might reduce demyelination in juvenile (onset between two and 14 years) and adult forms of MLD when performed as early as possible 3,4,5,16 . A recent case control study confirmed that HSCT, at a presymptomatic or early symptomatic stage of juvenile MLD, is associated with disease stabilization 10 .…”

mentioning

confidence: 93%

“…In addition, HSCT has been mostly indicated for the cerebral form (CALD) of the peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD) 2,3,4,5,6,7,8,9,10 . Considering that transplant-related mortality has declined to 10% and the rate of engraftment has substantially improved in recent years 11,12 , risk of transplant is worthwhile in contrast to the certainty that the natural history of these disorders will lead to dementia, decorticate or vegetative states and death, some years after onset.…”

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confidence: 99%

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Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

Saute

Souza

Poswar

et al. 2016

Arq. Neuro-Psiquiatr.

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Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD). Objective To describe survival and neurological outcomes after HSCT for these disorders. Methods Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

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Metachromatic Leukodystrophy and Globoid Cell Leukodystrophy

Gieselmann¹,

Wenger²,

Krägeloh‐Mann³

2022

Lysosomal Storage Disorders

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Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients

Cited by 111 publications

References 32 publications

Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy

Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

Metachromatic Leukodystrophy and Globoid Cell Leukodystrophy

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