Stem cell transplant is a safe and effective procedure to halt disease progression in patients with adult-onset forms of adrenoleukodystrophy (ALD), a study says.
The study, “Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy,” was published in the journal Brain Communications.
ALD is a rare neurodegenerative disorder caused by mutations in the ABCD1 gene. There are different types of ALD, depending on the age of disease onset and the type of symptoms it presents.
In child-onset cerebral ALD (childhood CALD), the loss of myelin — the fatty substance that protects nerve cells, and whose loss leads to neuron degeneration — and brain inflammation quickly set in once patients start experiencing the first neurological symptoms of the disorder.
For this particular form of the disease, a hematopoietic stem cell transplant (HSCT) — a procedure in which hematopoietic stem cells (blood cell precursors) are collected from the bone marrow or peripheral blood of a donor and inserted into a patient — has proved to be an effective form of treatment to stop CALD progression when performed at its earliest stages.
However, for adult-onset forms of CALD, the effectiveness and safety of HSCT has not been established.
To tackle this issue, a team led by researchers at the University of Tokyo, in Japan, carried out a prospective study to assess the clinical efficacy and safety of HSCT in patients with adolescent- and adult-onset cerebral or cerebello-brainstem forms of ALD. Preference was given to those who were still at the early stages of the disease.
A total of 45 men with ALD were enrolled in the single-center study from September 2003 to October 2018, and followed for an average period of 5.2 years. Of these, 25 were considered for HSCT, and 12 underwent the procedure. Patients were excluded from undergoing HSCT either because they were already at advanced stages of the disease and did not meet the inclusion criteria, or because they declined.
Investigators analyzed and compared survival rates of the 12 patients who underwent HSCT to those of eight patients who initially were considered, but did not undergo the procedure (control group). Neurological and MRI findings also were evaluated among those who underwent the stem cell transplant.
All 12 patients who underwent HSCT lived to date, with a median follow-up of 28.6 months (more than two years). In contrast, six of the eight patients who did not receive the transplant died after a median of 69.1 months (range 16.0 to 104.1 months) after having their first brain lesions.
These findings confirmed that HSCT increased the chances of survival in patients with adolescent- and adult-onset forms of ALD.
In all patients who received HSCT, neurological symptoms including difficulty talking, swallowing, and walking, stabilized or were partially alleviated following the transplant. Moreover, brain MRI scans revealed that brain lesions in these patients either stabilized, shrank, or completely disappeared following HSCT.
No severe infections or other serious complications were observed in patients after HSCT.
“The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination [myelin loss] in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages,” researchers wrote.
The team emphasized, however, that additional studies are needed to optimize the HSCT procedures in this patient population.
