Stem cell transplant may help reduce chronic inflammation in MS

Some paramagnetic rim lesions (PRLs) — MRI findings linked to chronic inflammation — disappeared in the brains of adults with multiple sclerosis (MS) after they underwent an autologous hematopoietic stem cell transplant (aHSCT), a small study found. No new PRLs appeared during follow-up.

The findings contrast with an earlier study that found no PRLs disappeared after aHSCT during a shorter follow-up period. Both studies were small, and the new findings are exploratory.

“Given the reported long persistence of PRLs, these data indicate that [aHSCT] may accelerate their disappearance,” the researchers wrote in “Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis,” published in the Multiple Sclerosis Journal.

MS causes inflammatory damage in the brain and spinal cord. This damage appears as spots called lesions on MRI scans. Over time, it can lead to neurological symptoms and disability.

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Inflammation can continue within existing MS lesions. On MRI scans, this may appear as a rim of iron-containing immune cells around the edge of a lesion, known as a paramagnetic rim lesion (PRL). PRLs have been linked to a higher risk of developing MS symptoms in people with MS-like lesions but no symptoms and may help in diagnosing MS early.

Currently approved disease-modifying treatments (DMTs) work by reducing immune activity and inflammation in MS. This can help prevent new lesions from forming, but available studies suggest these treatments have little or no effect on PRLs.

In a recent study, researchers examined whether aHSCT, a type of stem cell therapy, could help resolve PRLs. The procedure involves collecting a patient’s own blood-forming stem cells and returning them to the body after intensive chemotherapy to reset the immune system. However, none of the PRLs disappeared during a median follow-up of 15 months among five patients with follow-up scans.

Researchers in Italy then examined whether following patients for longer would reveal different results.

The researchers reviewed records from 30 adults, ages 27–53 at transplantation, who had undergone aHSCT. Of these, 60% had relapsing-remitting MS, while the others had secondary progressive MS. Twelve had brain MRI scans both before and after the transplant (pre/post-aHSCT group), while 18 had scans only after the procedure (post-aHSCT group).

In the pre/post-aHSCT group, five of 12 people (42%) had at least one PRL on their MRI scan before transplantation, with between one and 18 PRLs per person. During a median MRI follow-up of 21 months (range, seven to 74 months), PRL counts decreased in two of these five people (40%). Overall, five of the 26 PRLs (19%) disappeared.

One PRL disappeared 24 months after transplantation in one patient, while four disappeared by 36 months in another. The rims gradually faded before disappearing, and no new PRLs appeared. However, new T2 lesions were detected in two patients: three lesions caused by demyelination (damage to the protective covering around nerve fibers) in one patient and four ischemic lesions (areas of damage caused by reduced blood flow) in another.

Disability outcomes after stem cell transplantation

In the pre/post-aHSCT group, disability worsened in three of 12 patients (25%) over a median follow-up of 27 months, based on scores on the Expanded Disability Status Scale (EDSS), a measure of disability in MS. At three years after transplant, the estimated proportion of patients without worsening disability was 100% among those with four or more PRLs before treatment, compared with 51% among those with fewer than four. However, the difference was not statistically significant. One patient who had 18 PRLs before transplant showed sustained improvement in EDSS scores over six years of follow-up.

In the pre/post-aHSCT group, patients with more PRLs before transplantation tended to have greater disability, based on EDSS scores. However, in the separate post-aHSCT group, researchers found no association between PRL counts measured on MRI scans after transplantation and EDSS disability scores.

In the post-aHSCT group, seven of 18 patients (39%) had at least one PRL on their first MRI scan included in the study, with one to six PRLs per person. These first scans were taken between five and 142 months (nearly 12 years) after transplantation. The median MRI follow-up was 51 months (range, six to 57 months).

During follow-up, PRL counts decreased in four of the seven patients who had PRLs (57%). Overall, 10 of the 20 PRLs (50%) disappeared. No new PRLs, gadolinium-enhancing lesions (signs of active inflammation), or new T2 lesions were detected. In this group, EDSS scores worsened in nine of 18 patients (50%) over a median clinical follow-up of 80 months (range, 11 to 184 months, or about 15 years).

The researchers concluded that their exploratory study shows “[aHSCT] can promote PRL disappearance.” They plan larger studies to determine whether PRLs can help predict how patients respond to aHSCT and other treatments that act within the central nervous system.