Exploring the therapeutic potential of autologous hematopoietic stem cell transplantation in progressive multiple sclerosis-a systematic review

Abstract

Background and purpose: The aim was to determine the value of autologous haematopoietic stem cell transplantation (aHSCT) as a therapeutic intervention for progressive multiple sclerosis (PMS) based on a systematic review of the current literature.

Methods: All studies from the databases PubMed and Google Scholar published in English before February 2024 which provided individual data for PMS patients were systematically reviewed. PICO was defined as population (P), primary progressive MS and secondary progressive MS patients; intervention (I), treatment with aHSCT; comparison (C), none, disease-modifying therapy treated/relapsing-remitting MS cohorts if available; outcome (O), transplant-related mortality, progression-free survival (PFS) and no evidence of disease activity.

Results: A total of 15 studies met the criteria including 665 patients with PMS (74 primary progressive MS, 591 secondary progressive MS) and 801 patients with relapsing-remitting MS as controls. PFS data were available for 647 patients. PMS patients showed more severe disability at baseline than relapsing-remitting MS patients. The average transplant-related mortality for PMS in 10 studies was 1.9%, with 10 deaths in 528 patients. PFS ranged from 0% to 78% in PMS groups 5 years after treatment initiation, demonstrating a high variability. No evidence of disease activity scores at 5 years ranged from 0% to 75%.

Conclusion: Based on the available data, aHSCT does not halt progression in people with PMS. However, there appears to be evidence of improved outcome in selected patients. Due to the heterogeneity of the available data, more comprehensive clinical trials assessing the efficacy of aHSCT across different patient groups are urgently needed to reduce variability and improve patient stratification.

Keywords: autologous hematopoietic stem cell transplantation; no evidence of disease activity; progression‐free survival; progressive multiple sclerosis; transplant‐related mortality.

FIGURE 1

Transplant‐related mortality in PMS. Depicted are the TRM rates in PMS for each of the analysed studies, along with the resulting pooled value. Two studies did not report a TRM for PMS patients and three studies were excluded as subsequent studies exist. The points represent the TRM of the associated study, and the square represents the pooled TRM. The numbers in parentheses indicate the sample size of PPMS and SPMS patients in each cohort. PMS, progressive multiple sclerosis; PPMS, primary progressive multiple sclerosis; SPMS, secondary progressive multiple sclerosis; TRM, transplant‐related mortality.

FIGURE 2

Overview of the PFS in PMS compared to RRMS. PFS rates of individual studies segmented by the MS disease courses are depicted. Time is measured in years after therapy initiation. Purple lines represent RRMS, green lines symbolize SPMS and yellow lines PPMS. The symbols indicate the corresponding study. A solid black line depicts the PFS average for PMS cohorts, whilst a dotted line represents RRMS cohorts. The numbers in parentheses indicate the sample size of PPMS and SPMS patients in each cohort. PFS, progression free survival; PMS, progressive multiple sclerosis; PPMS, primary progressive multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

FIGURE 3

NEDA‐3 in PPMS, SPMS and RRMS cohorts. The NEDA‐3 rates reported in the analysed studies, categorized by the MS disease course, are depicted. Time is measured in years after therapy initiation. The purple lines represent RRMS, green lines symbolize SPMS and the yellow line symbolizes PPMS. The symbols indicate the corresponding study. The numbers in parentheses indicate the sample size of PMS patients in each cohort. NEDA, no evidence of disease activity; PMS, progressive multiple sclerosis; PPMS, primary progressive multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.