Original Title: Autolog hematopoietisk stamcelletransplantasjon ved multippel sklerose

Authors' objectives: To perform a systematic review of efficacy and safety, an economic evaluation and discuss ethical considerations related to HSCT for MS.

Authors' results and conclusions: RESULTS: The literature search identified 2409 publications, of which 23 studies about efficacy and safety were included in the systematic review. We reviewed and summarized the results of controlled trials, registry studies, and case series with a predominance of patients with RRMS or where data for the RRMS group could be extracted; a total of nine studies. For the other 13 case series which mainly had included patients with secondary progressive MS (SPMS) and primary progressive PPMS (PPMS), the results are not described in the text, but presented in tables in the attachment to the report. 11 Executive summary (English) Key Findings: We identified only one very small RCT in our search. The RCT had a non-relevant control group, and only two out of nine patients in the intervention group had RRMS. The other studies, without control groups, were: one larger registry study (345 patients with MS) and seven smaller case series (433 patients with MS where as 274 had RRMS). In the registry study the results were not reported for the various subgroups of MS. The registry study reported a 100-day mortality rate of 2 percent with confidence intervals from 0 to 4 percent among 345 patients with MS. Serious side effects associated with immunosuppression and toxicity occurred in the majority of patients in the early stages (within 100 days). In the later stages serious adverse events such as infections, sepsis, other autoimmune diseases or haemorrhages were common, but it is not possible to give exact numbers. The case series reported a stabilization or improvement in neurological status, assessed as less than 1 point increase on the EDSS, in 63 to 89 percent of the patients after three years. Deterioration was reported in 11 to 37 percent of the patients after three years, and in 56 percent (with 10 of 18) after seven years. Over three to five years relapse-free survival was reported to be between 57 and 86 percent, progression-free survival between 45 and 91 percent, MRI event-free survival between 85 and 100 percent, and disease-free survival between 68 and 78 percent. The extent to which the same patients are included in several studies is uncertain, and the number of patients studied decreased significantly for each year of follow up. We assessed the quality of the evidence as low for mortality at 100 days and very low for all other outcomes. CONCLUSION: The evidence for treatment with autologous hematopoietic stem cell transplantation for MS is of very low quality (except for mortality at 100 days), and there is considerable uncertainty related to the results. We found no controlled studies, except for a very small RCT, and it was not possible to draw firm conclusions on the basis of the published material. The studies without control groups reported that: mortality at 100 days after HSCT is possibly similar to or below 2 percent, that serious side effects and adverse events are common, and appeared in most of the patients in the early stages, that disease progression can be delayed or stopped in a selected group of patients in an observation period of three years. Results after this period were lacking. 13 Executive summary (English) Health-related quality of life was only studied in parts of the sample in a few studies. It is emphasized in the publications that the results from the patient series must be confirmed by controlled studies. It is not possible to conclude anything about the cost-effectiveness of the intervention because studies of effect are lacking. It was therefore impossible to perform a complete health economic analysis. The main ethical considerations are associated with a heterogeneous progression and significant uncertainty of benefit versus harm

Authors' methods: We performed a systematic search for controlled and non-controlled studies, and registry studies on the 02.17.2015. The inclusion criteria were: persons above eighteen years with MS. Intervention: autologous hematopoietc stem cell transplantation (HSCT). Comparison: pharmacological treatment or no treatment. Outcomes: mortality, adverse events, disease progression as assessed by the «Expanded disability status scale» (EDSS), relapse- and disease-free survival, number of or new lesions observed on MRI, and health-related quality of life. Study design: Randomized controlled trials, controlled prospective and retrospective studies, and studies without control groups (case series) with participant number of more than 10.

Project Status: Completed

Year Published: 2015

URL for published report: https://www.fhi.no/en/publ/2015/autologous-hematopoietic-stemcell-transplantation-for-multiple-sclerosis/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Pubmed ID: 28510398

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo