Unrelated umbilical cord blood transplant for juvenile metachromatic leukodystrophy: A 5-year follow-up in three affected siblings

Abstract

Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a five-year period with serial neurological exams, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first two years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease.

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

“…9,28 As affected, untreated sibling controls with MLD fared drastically worse than the HSCT-treated patients, and in view of the agreement between our results and the findings in other publications, we conclude that HSCT halted the progression of adult and late-onset juvenile MLD. If transplantation is considered, it should be performed as soon as possible after diagnosis.…”

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

“…However, HSCT results in patients with juvenile MLD are inconsistent and controversial. While several studies showed stabilization and even improvement for some aspects, such as MRI, 10-18 others did not. 19,20 It was suggested that this therapy is not an option in MLD.…”

“…21,22 The varying results after HSCT in juvenile patients are in part due to different clinical disease stages at transplantation. In fact, increasing evidence indicates less favorable outcome when HSCT is performed in advanced disease, 10,11,19,[23][24][25] whereas patients who receive HSCT early during their disease course benefit most. 18,25-27 Transplantation-related mortality (TRM) is a serious concern and may be as high as 37% in patients with juvenile MLD.…”

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

“…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.…”

“…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 .…”