Early diagnosis of cerebral adrenoleukodystrophy (CALD), followed by stem cell treatment, can halt disease progression and improve patients’ quality of life, a study finds.
The study, “Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with and without Hematopoietic Stem Cell Transplantation,” was published in Biology of Blood and Marrow Transplantation.
CALD is a progressive, often fatal, neurodegenerative disease characterized by major functional disabilities (MFDs), including loss of communication and voluntary movement, blindness, and incontinence. The disorder is caused by mutations in the ABCD1 gene located on the X chromosome, which provides instructions for the production of the adrenoleukodystrophy (ALD) protein.
The only way of stopping disease progression is a treatment called allogeneic hematopoietic stem cell transplantation (HSCT). This technique is based on the transplant of hematopoietic stem cells — cells that can form all types of blood cells in the body — from a genetically similar donor, usually a close relative of a patient.
“Although HSCT is effective and outcomes are favorable when performed in early-stage CALD, it is associated with serious and sometimes fatal complications, including infection, graft-versus-host disease, (GVHD, a serious complication in which the transplanted cells start attacking the host’s body), and graft failure or rejection,” the researchers said.
For this reason, alternative treatment options that overcome these limitations are urgently needed.
To develop these approaches, scientists must have “a thorough understanding of [CALD] natural history and robust methods for objectively measuring key outcomes, including maintenance of neurologic functioning following treatment with HSCT,” the team stated.
In this large, multicenter retrospective review study, the researchers set out to characterize the natural history of CALD, as well as patients’ clinical outcomes after undergoing HSCT.
The HSCT clinical outcome was determined based on MFDs that had the greatest impact on the patients’ ability to perform tasks independently. The neurological function score was used to assess neurological symptom progression, and the Loes magnetic resonance imaging (MRI) score was used to determine how much demyelination (the loss of myelin in nerve cells) occurred.
The study analyzed the clinical records of 137 CALD patients — 72 who went untreated, and 65 who underwent HSCT — from five sites in the U.S. and France.
Study findings showed that patients from the HSCT group had higher (78%) overall survival rates five years after their diagnosis, compared to those from the untreated group (55%).
In addition, patients with active neurological lesions at the start of the study who underwent HSCT (84%) were more likely to be free of MFDs over the next two years, compared to those (29%) who did not receive stem cell transplants.
In the HSCT group, 12 of the 65 patients (18%) died a year later, mainly because of disease progression (44%) and infection (31%). The most common adverse events associated with HSCT included infection (29%), acute GVHD (31%), and chronic GVHD (7%). Moreover, in 18% of the patients (12 of 65), the stem cell transplant failed on the first attempt.
The data also showed that positive clinical outcomes in HSCT patients were associated with high patient-donor compatibility, and the absence of GVHD. Treatment at early stages of the disease was linked to MFD-free survival.
The presence of active neurologic lesions that were visible on the MRI is a strong indication of disease progression in untreated patients.
“This study confirms HSCT as an effective treatment for CALD when performed early,” the researchers concluded.
Survival without MFDs should be a relevant treatment goal, rather than only assessing overall survival as an indicator of treatment success, with the team stating, “Two-year MFD-free survival is a useful clinical outcome for evaluating the efficacy of treatments for CALD.”