Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden

Sammanfattning: This thesis investigated the efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT) as a treatment of multiple sclerosis. This thesis demonstrates that when compared to one of the most powerful disease-modifying drugs (DMDs), specifically alemtuzumab (ALZ), AHSCT is able to hold its ground. Patients that were treated with AHSCT were more likely to maintain NEDA-3 or freedom from disease in three parameters (no confirmed disability worsening, clinical relapses or MRI events) versus those treated with ALZ. The three year post-treatment Kaplan-Meier (KM) estimates of NEDA-3 were 88 % for AHSCT and 37 % for ALZ treated patients.  With AHSCT, adverse events were more common in the first three months, as is expected with an intense one-time treatment. ALZ, though powerful and with little early adverse effects, has more late adverse effects instead, namely thyroid disease. At 3 years post-treatment, the KM-estimates of thyroid disease were 21 % for AHSCT and 46 % for ALZ. We then sought to address potential concerns in using AHSCT on patients previously treated with potent DMDs like alemtuzumab, cladribine or rituximab. The concern lay in the fact that these powerful DMDs have long-lasting effects on the immune system. We found that the rates of treatment-related and long-term complications were the same for all patients regardless of previous use of DMDs. This finding therefore allays those concerns: previous treatment with a powerful DMDs need no longer be a possible deterrent to giving a patient AHSCT.Using a series of CSF biomarker studies, we gauged treatment efficacy. We showed that CNS inflammation is measurably affected by treatment, especially when it comes to AHSCT. Post-AHSCT treatment, many of the proteins we studied decreased towards the direction of healthy individuals, as early as the first year after treatment and remained so during subsequent follow-ups. Additionally we saw that tissue-injuring disease processes, for example represented by biomarkers like NFL and MBP, normalized for the majority of patients. These promising results suggest that tissue-injury could possibly be stopped in its tracks with AHSCT.  Finally, we observed that biomarkers of B- and T-cell activation also became normalized, showing that AHSCT treatment also shuts down acute inflammation. All of these factors together explain why patients treated with AHSCT are able to maintain NEDA-3 so effectively even when compared to one of the most potent drugs available. These results compellingly illustrate that AHSCT treatment yields quantifiably long-lasting and beneficial effects that are not commonly seen with other available treatments for MS. Therefore, use of AHSCT should be advocated, promoted and utilized more for the benefit of patients and society as a whole.