Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report

Abstract

Cerebral adrenoleukodystrophy (cALD) remains a devastating neurodegenerative disease; only allogeneic hematopoietic cell transplantation (HCT) has been shown to provide long-term disease stabilization and survival. Sixty boys undergoing HCT for cALD from 2000 to 2009 were analyzed. The median age at HCT was 8.7 years; conditioning regimens and allograft sources varied. At HCT, 50% demonstrated a Loes radiographic severity score > 10, and 62% showed clinical evidence of neurologic dysfunction. A total of 78% (n ‫؍‬ 47) are alive at a median 3.7 years after HCT. The estimate of 5-year survival for boys with Loes score < 10 at HCT was 89%, whereas that for boys with Loes score > 10 was 60% (P ‫؍‬ .03). The 5-year survival estimate for boys absent of clinical cerebral disease at HCT was 91%, whereas that for boys with neurologic dysfunction was 66% (P ‫؍‬ .08). The cumulative incidence of transplantationrelated mortality at day 100 was 8%. Posttransplantation progression of neurologic dysfunction depended significantly on the pre-HCT Loes score and clinical neurologic status. We describe the largest single-institution analysis of survival and neurologic function outcomes after HCT in cALD. These trials were registered at www.clinicaltrials.gov as #NCT00176904, #NCT00668564, and #NCT00383448. (Blood. 2011;118(7): [1971][1972][1973][1974][1975][1976][1977][1978]

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

“…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 .…”

“…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.…”

Post‐transplant adaptive function in childhood cerebral adrenoleukodystrophy

“…In particular, the association between MRI severity with disease progression and neurological/neurocognitive outcomes is well‐established 10, 28, 29. In addition, previous studies reported that boys scoring <80 on the Wechsler Performance IQ scale (a subscale available on older versions of this measure, which assessed visual reasoning and processing speed) at the time of HSCT were at greater risk for worsening neurological status after transplant 7, 8. These reports underscored the importance of initiating intervention as early as possible upon detection of active cerebral disease.…”

“…Each baseline study was reviewed by a board‐certified neuroradiologist (D.N.) and characterized according to the extent of white matter signal abnormality and atrophy using a 0–34 point severity scale developed by Loes et al6 Higher scores denote more extensive cALD, with a pre‐HSCT threshold of 10 or more points indicating “higher risk” disease status 8…”

Mild phenotype in an adult male with X‐linked adrenoleukodystrophy – case report

“…Failure to detect X‐ALD may hamper the identification of affected relatives, thereby missing opportunities for early detection of Addisonism in boys and follow‐up of boys in order to provide hematopoietic stem cell transplantation in case of cerebral leukodystrophy 15 and genetic counseling.…”