AHSCT for Multiple Sclerosis

What is AHSCT?

Autologous haematopoietic stem cell transplantation (AHSCT) is an immune-reconstitution treatment used in selected patients with multiple sclerosis (MS).

The treatment combines intensive immune suppression with the collection and later reinfusion of the patient's own blood-forming stem cells.

The objective is to substantially suppress the immune populations driving inflammatory MS activity and allow a renewed immune repertoire to develop.

AHSCT should not be confused with regenerative stem-cell therapy. Its primary purpose is to control immune-mediated inflammation; it does not directly regenerate established neurological damage.

How Does AHSCT Work?

AHSCT is a multistep procedure. Because the transplant is autologous, the patient's own haematopoietic stem cells are used rather than cells from a donor.

The treatment generally involves four main stages:

• Mobilization: medication is used to move CD34+ haematopoietic stem cells from the bone marrow into the bloodstream.
• Stem Cell Collection: the cells are collected from the blood by leukapheresis and cryopreserved for later use.
• Conditioning: chemotherapy is administered to substantially deplete the existing immune system.
• Stem Cell Reinfusion and Recovery: the stored autologous stem cells are returned to the patient to restore normal blood-cell production while the immune system gradually rebuilds.

Immune recovery continues well beyond hospital discharge. Different immune-cell populations recover at different rates, and complete immune reconstitution can take months or longer.

Which Patients May Be Considered?

According to the evidence reviewed by Muraro and colleagues, the strongest results have been observed in carefully selected patients with highly active inflammatory relapsing-remitting multiple sclerosis (RRMS).

A potential candidate may typically have characteristics such as:

• Relapsing-remitting multiple sclerosis with significant inflammatory activity.
• Recent clinical relapses despite appropriate treatment.
• Recent MRI evidence of active disease.
• Failure of an approved high-efficacy disease-modifying therapy.
• Younger age, with the 2017 review identifying patients below approximately 45 years as a more favorable group.
• Relatively shorter disease duration, generally below approximately 10 years in the profile described by the review.
• Low-to-moderate neurological disability and preserved mobility.
• No major medical condition that would substantially increase transplantation risk.

AHSCT appears less beneficial when disability is mainly caused by established neurodegeneration rather than continuing inflammatory disease activity.

Potential Benefits

• Strong suppression of MS relapses in appropriately selected patients.
• Reduction of new inflammatory MRI activity.
• Potential long-term disease stabilization.
• Possibility of neurological improvement in some patients with inflammatory RRMS.
• A one-time immune-reconstitution strategy rather than continuous disease-modifying treatment.

Studies summarized in the 2017 review reported high rates of no evidence of disease activity (NEDA) in selected AHSCT cohorts. However, comparisons with drug therapies were largely indirect and involved different patient populations and study designs.

Who May Be Less Suitable?

The benefit-risk balance becomes less favorable when multiple sclerosis is predominantly progressive and no longer shows significant inflammatory activity.

Factors that may reduce suitability include:

• Advanced non-inflammatory progressive multiple sclerosis.
• Higher established neurological disability.
• Older age.
• Long disease duration.
• Significant cardiac, renal, pulmonary or liver disease.
• Active infection.
• Other substantial medical conditions that increase transplantation risk.

Possible Side Effects and Risks

AHSCT intentionally produces profound immunosuppression. For this reason, it is an intensive medical treatment with potentially serious complications.

Possible monitored risks include:

• Low blood-cell counts following conditioning.
• Neutropenic fever.
• Bacterial or fungal infections.
• Viral reactivation.
• Conditioning-related organ toxicity.
• Temporary or permanent fertility impairment.
• Secondary autoimmune disorders.
• Possible long-term risk of secondary malignancy.
• Need for infection prophylaxis, monitoring and revaccination during immune recovery.

Treatment-related mortality reported in the literature reviewed by Muraro and colleagues decreased substantially over time, which the authors associated with improved patient selection, transplant protocols, center experience and supportive care.

Recovery After AHSCT

AHSCT involves more than the transplantation procedure itself. Patients require careful monitoring during the period of neutropenia and early immune recovery.

The 2017 review describes a typical inpatient period of approximately three weeks, although the exact duration varies according to the protocol, patient condition and clinical course.

Immune recovery continues for months after discharge. Patients may require antimicrobial prophylaxis, infection monitoring, revaccination and structured long-term neurological and haematological follow-up.

Required Documents for Medical Evaluation

• Recent neurology medical summary.
• Confirmation of the type and duration of multiple sclerosis.
• Recent brain and spinal MRI examinations.
• Previous MRI examinations for comparison, when available.
• Details and dates of recent MS relapses.
• Current neurological disability assessment, including EDSS when available.
• Complete history of previous disease-modifying treatments.
• Recent blood tests.
• Kidney and liver function tests.
• Relevant cardiac, pulmonary and infectious-disease evaluations when available.
• Information about other medical conditions and current medications.