Allogeneic hematopoietic stem cell transplantation in patients with childhood cerebral adrenoleukodystrophy: A single‐center experience “Better prognosis in earlier stage”

Abstract

Background: ALD is a rare X-linked peroxisomal metabolic disorder with many distinct phenotypes of disease that emerge on a wide scale from adrenal insufficiency to fatal cALD which progresses to a vegetative state within a few years. Currently, HSCT is the only treatment method known to stabilize disease progression in patients with cALD. In this study, we aim to report our HSCT experience in patients with cALD and the factors that determine the success of HSCT, as a single-center experience. Methods:The study cohort involves 23 boys with cALD and three patients with ALD trait and new-onset abnormal behavior who underwent allogeneic HSCT between January 2012 and September 2019 in our transplantation center. Loes scoring, NFS, scale and MFD were performed for evaluating the severity of the cerebral disease.The study cohort was divided into two groups according to baseline NFS and Loes score: early-stage (NFS ≤ 1 and Loes score <9) and advanced stage (NFS > 1 or Loes score ≥9). Results:The pretransplant stage of disease impacted both OS and MFD-free survival.The estimated OS and MFD-free survival at 3 years in patients with advanced disease were 46.1% (95% CI 19.0-73.2) and 23.1% (95% CI 0.2-46.0), respectively, and all patients with the early disease were alive (p: .004) and MFD-free (p < .001) at 3 years. Conclusion:This study demonstrated that early HSCT is vital in patients with cALD.The early-stage disease had a significant survival advantage and free from disease progression after HSCT.

The experiences of parents of children diagnosed with cerebral adrenoleukodystrophy

“…As previously reported, treatment by HSCT leads to statistically greater rates of survival and rates of survival free of major functional disabilities among those with early disease as compared to those with advanced disease (Kühl et al, 2018; Yalcin et al, 2021), highlighting the critical importance of early diagnosis. In the United Kingdom and elsewhere, an initial diagnosis of ALD within a family will lead to a programme of extended family testing to identify others at risk of disease (Bezman et al, 2001).…”

“…A scoring system (the Loes score) is used to make decisions about whether to proceed to transplant. Several multinational prospective studies have assessed treatment outcomes of children receiving HSCT and consistently reported statistically greater rates of survival and rates of survival free of major functional disabilities among those with early disease as compared to those with advanced disease (Kühl et al, 2018; Yalcin et al, 2021).…”

Intrathecal administration of mesenchymal stem cells in patients with adrenomyeloneuropathy

“…There is no approved treatment for ALD. In early cases of CALD, allogenic hematopoietic stem cell transplantation (HSCT) is recommended to prevent disease progression and long-term stabilization (26,27). Although the direct mechanism of HSCT activity is not clear, it is assumed that transplanted HSCs deliver the cellular source of the intact ABCD1 gene and corrected VLCFA ratio (12).…”

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening

“…HCT has been effective in treating CCALD since the early 1990 s and is presently the standard of care 44,45 . Successful treatment typically halts the long‐term advancement of cerebral demyelination, although it is common to observe some degree of clinical progression in the months following HCT as disease stabilizes 11,32,46,47 . In terms of neurocognitive outcomes, studies have consistently demonstrated that HCT performed early in the disease process results in better preservation of abilities.…”

“…44,45 Successful treatment typically halts the long-term advancement of cerebral demyelination, although it is common to observe some degree of clinical progression in the months following HCT as disease stabilizes. 11,32,46,47 In terms of neurocognitive outcomes, studies have consistently demonstrated that HCT performed early in the disease process results in better preservation of abilities. Shapiro and colleagues were the first to report long-term neurocognitive outcomes after HCT among a set of 8 boys with CCALD treated before disease was advanced.…”