Patients who benefit most from autologous hematopoietic stem cell transplantation (AHSCT) compared to high-efficacy disease-modifying therapies (DMTs) are typically those with aggressive, highly active multiple sclerosis (MS) that has not responded well to conventional or even high-efficacy DMTs. AHSCT is especially advantageous for patients in the early stages of relapsing-remitting MS (RRMS) who exhibit frequent relapses and rapid accumulation of disability despite treatment with potent DMTs. These patients often have inflammatory disease activity evident on MRI scans and clinical assessments, indicating ongoing immune system attacks on the central nervous system.
AHSCT works by essentially “resetting” the immune system. The procedure involves harvesting the patient’s own hematopoietic stem cells, administering high-dose immunosuppressive therapy to eliminate the malfunctioning immune cells, and then reinfusing the stem cells to regenerate a new, less aggressive immune system. This approach targets the root cause of MS — the autoimmune attack — more aggressively than DMTs, which primarily modulate or suppress immune activity without fully eradicating the autoreactive immune cells.
Patients with highly active RRMS who have failed multiple lines of DMTs, including high-efficacy agents like alemtuzumab or cladribine, are prime candidates for AHSCT. The treatment has shown superior outcomes in terms of progression-free survival and relapse reduction compared to conventional DMTs. For example, clinical trials have demonstrated that AHSCT can achieve progression-free survival rates around 90% at five years, compared to much lower rates with standard DMTs. This means that patients undergoing AHSCT are far less likely to experience worsening disability over several years.
However, AHSCT is not typically recommended for patients with progressive forms of MS without active inflammation, such as primary progressive MS (PPMS) or secondary progressive MS (SPMS) without relapses. These patients tend to have neurodegeneration that is less driven by active immune attacks and more by chronic damage, which AHSCT does not effectively address. In such cases, high-efficacy DMTs may still be used to slow progression or manage symptoms, but the benefits are generally more modest.
Another important consideration is the patient’s overall health and ability to tolerate the intensive immunosuppressive conditioning required for AHSCT. Because the procedure involves high-dose chemotherapy, it carries risks including infections, organ toxicity, and in rare cases, treatment-related mortality. Therefore, younger patients with fewer comorbidities and good functional status are better candidates. Older patients or those with significant disability or other health issues may face higher risks and less benefit.
In summary, the patients who benefit most from AHSCT versus high-efficacy DMTs are those with:
– Highly active relapsing-remitting MS characterized by frequent relapses and MRI activity despite treatment with potent DMTs.
– Early-stage disease with inflammatory activity rather than advanced neurodegeneration.
– Good overall health and ability to tolerate intensive immunosuppression.
– Failure or intolerance of multiple prior DMTs, including high-efficacy agents.
For these patients, AHSCT offers a chance for long-term remission and significant reduction in disease progression by fundamentally altering the immune system, whereas high-efficacy DMTs primarily control disease activity without fully resetting immune function. Conversely, patients with progressive MS without active inflammation or significant comorbidities are more likely to benefit from continued use of high-efficacy DMTs or other symptomatic treatments rather than AHSCT.
