Hematopoietic Stem Cell Transplantation in the Leukodystrophies: A Systematic Review of the Literature

Abstract

Objective The objective of this study is to systematically review the literature on worldwide numbers of leukodystrophy patients undergoing hematopoietic stem cell transplantation (HSCT) as well as the safety and efficacy of the procedure in this patient population. Materials and Methods A PubMed and EMBASE search up to June 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria. The effect estimates of HSCT upon survival in early-stage disease versus late-stage disease were compared. Results One hundred and fifty-two studies qualified for inclusion and reported on a total of 689 patients. Study quality ranged from poor to good; no study was rated excellent. Small sample sizes limited most studies. Meta-analysis in a subset of larger studies indicates that transplantation in earlier stages of disease fairs better than in the late stages. Beyond survival, little longitudinal data on functional outcome is reported and neurological outcome is sparse. Conclusion Further studies are needed to determine the neurological outcome following HSCT in the leukodystrophies. HSCT in the early stages of cerebral disease is still recommended for select leukodystrophies.

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

“…To date, HSCT is a unique therapy with potential to bring long-term survival and neurological stabilization for CALD and for some lysosomal storage disorders with brain involvement. Around 500 children with MPS-IH, 114 with MLD, and 465 with CALD underwent HSCT worldwide before 2012 11,12 . In the same period, South American HSCT procedures were described in seven CALD patients (the follow-ups of three of them were reported by Jardim et al 17 ), six MPS and one Gaucher disease type 1 25 .…”

“…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.…”

“…There is consensus about the efficacy of HSCT when performed early in life for MPS-IH 9,13,14 and at early stages in CALD 6,7,12,15 . 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 .…”

Evidence for improved survival in postsymptomatic stem cell‐transplanted patients with Krabbe's disease

“…In addition, it must be emphasized that there is compelling evidence that afflicted children improve substantially if treated presymptomatically, although the evidence for a benefit from postsymptomatic treatment compared with no treatment is inconclusive (Escolar et al, 2005;Musolino et al, 2014). The latter question is still open.…”

“…Additional study of survival outcome in symptomatic patients treated with HSCT is required. HSCT has significant morbidity and mortality, and, although it improved survival and development in presymptomatic children, improvement was not statisti-cally significant in children transplanted after onset of symptoms compared with patients who were not transplanted (Escolar et al, 2005;Musolino et al, 2014). The latter result, however, was based on a small sample, with presumably low power and without controlling for age at onset of symptoms.…”