Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis

Abstract

Objective:to examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting.Methods:retrospective cohort study on PwMS treated with AHSCT at two centers in London, UK, consecutively between 2012 and 2019 who had ≥ 6 months of follow-up or died at any time. Primary outcomes were survival free of MS relapses, MRI new lesions and worsening of expanded disability status scale (EDSS). Adverse events rates were also examined.Results:the cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS (RRMS). At baseline, the median expanded disability status scale (EDSS) was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6–85). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of subjects at 2 years and 85% at 4 years. EDSS progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. EBV reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplant-related deaths within 100 days (2.5%), all following fluid overload and cardiac or respiratory failure.Conclusions:efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher.Classification of evidence:this study is rated Class IV because of the uncontrolled, open-label design.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis Patients: Monocentric Case Series and Systematic Review of the Literature

“…The intermediate-intensity conditioning AHSCT was able to induce a consistent reduction in the gadolinium-enhanced (Gd + ) lesions up to 99% compared with the pre-treatment count using a triple dose of gadolinium (Gd) [35]. Similarly, in another study that analyzed 327 MRI scans of 23 patients treated with a high-intensity AHSCT regimen, no signs of MRI activity were detected in comparison with the high disease activity documented prior to AHSCT [27].…”

“…Indeed, the current literature shows that AHSCT is able to induce complete remission of clinical relapses in 70-100% of treated relapsing-remitting MS (RRMS) patients. In particular, the relapse-free survival rates ranged from 80% at 4 years to 100% at a median of 6.7 years of follow-up [27,32,34,35,41]. This massive anti-inflammatory effect was observed in MS patients with highly active disease prior to AHSCT, as shown by the median/mean annualized relapse rate (ARR) in the previous year ranging from 1.2 to 8 [27,32,34].…”

“…Several studies demonstrated that AHSCT is able to achieve progression-free survival values of up to 100% at 10 years, with a reduction of long-term disability progression in at least 40% of patients [34]. In particular, in RRMS patients, the progression-free survival ranged from 73% to 100% at 5 years, which was maintained for up to 10 years in one study [9,[33][34][35]. In another recent cohort where RRMS patients were treated with a BEAM+ATG conditioning protocol, disability-worsening-free survival was reached in 85.5% (range 76.9-94.1%) at 5 years and in 71.3% (range 57.8-84.8%) of patients at 10 years [36].…”

“…In a retrospective study of 120 MS patients (52% with progressive MS (secondary or primary)) treated with AHSCT, 90% at 2 years and 85% at 4 years showed no new MRI lesions, with a progression-free survival of about 75% at 2 years and 65% at 4 years [35]. In a recent Italian study, disability-worsening-free survival was 71.0% (range 59.4-82.6%) and 57.2% (range 41.8-72.7%) at 5 and 10 years [36].…”

Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party

“…Despite the efficacy of HSCT in MS, it remains associated with a treatment-related mortality risk ranging from none in some clinical trials and reports (41,47,48) to around 0.2% (49, 50), 1.4% (51), 2.5% (52) in larger series up to 4% in one trial of patients treated with a high intensity myeloablative regimen (46). Overall, there has been reduction in transplant-related mortality (TRM) over time (51,53), probably related to better patient selection and choice of conditioning regimen, which has permitted acceptance within the neurological community.…”