Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Abstract

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.

Efficacy of hematopoietic cell transplantation in metachromatic leukodystrophy: the Dutch experience

“…Hematopoietic cell transplantation (HCT) is a possible treatment, but systematic outcome data are lacking, due to the use of different eligibility criteria and protocols worldwide. [4][5][6][7][8][9][10][11][12] In order to assess HCT efficacy, we evaluated all 35 consecutive MLD patients presenting between 2004 and 2015 in our department, the Dutch Leukodystrophy Referral Center ( Figure 1A). …”

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

“…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 .…”

“…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.…”

Abnormalities of acid–base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients

“…Knowledge of this manifestation of the disease is of great relevance in view of new therapeutic approaches currently being tested for this disease, such as haematopoietic stem cell transplantation [15][16][17][18], gene therapy [11] and enzyme replacement strategies (ClinicalTrials.gov Identifier: NCT01510028). Indeed, along with the application of new and intense therapeutic opportunities to these patients, potential prolongation of their life expectancy and amelioration of their prognosis may render them more susceptible to episodes of acute acidosis due to the treatment-related and/or treatment-independent exposure to stressful situations.…”