Blood Stem Cell Transplant May Help Immune System Longer

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Treatment with an autologous hematopoietic stem cell transplant (aHSCT) seems to reboot the immune system in multiple sclerosis (MS) patients for at least three years, a small study found.

The study, “Sustained immunotolerance in multiple sclerosis after stem cell transplant,” was published in Annals of Clinical and Translational Neurology.

aHSCT is an intensive, experimental treatment approach that uses a person’s own (autologous) healthy blood stem cells (progenitors), which can develop into any type of blood cell, to stop MS-related immune attacks on the brain and spinal cord.

Hematopoietic stem cells are collected from a patient’s bone marrow and then infused back to the patient after a fairly aggressive chemotherapy regimen, which is given to kill their immune cells, including the cells that launch the erroneous immune attacks in MS.

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While aiming for a total reset of a person’s immune system, this one-time treatment has the potential to induce sustained periods of disease remission in people with relapsing forms of MS, including relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).

A team of researchers in Australia had shown previously that aHSCT could reboot the immune system in the body, with patients showing an increase in immunoregulatory cells (cells that dampen excessive immune responses) for at least one year.

“However, the mechanisms associated with durable treatment responses in MS require further elucidation,” the researchers wrote.

In the present study, the team sought to determine whether this restoration of an immune balance was maintained beyond one year, and whether the immune cells that are present at a certain time had a relationship with disease remission.

The study included 22 adults with RRMS or SPMS who received an aHSCT as part of a Phase 2 clinical trial (ACTRN12613000339752) and were followed for at least three years. These patients, median age 34, had failed to respond to first-line disease-modifying treatments. The study also included 18 age- and sex-matched healthy adults as controls.

When the researchers compared peripheral blood samples taken before aHSCT with those taken up to three years after aHSCT, they found that the blood became enriched in some populations of immune cells, called CD8 T-cells and CD19 B-cells.

Other populations of immune cells that play a role in inflammation also were reduced after three years, with most going from levels above those seen in healthy controls to levels significantly lower than in controls. This was accompanied by an increase in immunoregulatory cells, which are immune cells that work to control immune responses.

During the three years of the study, there were 17 patients who were deemed responders and five who failed to respond to aHSCT — based on the presence of a clinical relapse or imaging evidence of new lesions. Notably, only responders had a decrease in certain populations of pro-inflammatory immune cells at three years and an increase in regulatory T-cells at two years.

“AHSCT induces substantial recalibration of pro-inflammatory and immunoregulatory components of the immune system of MS patients for up to 36M [three years] post-transplant,” the researchers concluded.