Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives

Abstract

High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is a promising approach to treatment of multiple sclerosis (MS) patients. In this paper, we present the long-term outcomes of a prospective single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients: mean age-35 years old; male/female-39/60; median Expanded Disability Status Scale (EDSS) = 3.5; 43 relapsing/remitting MS, 56 progressive MS. No transplant-related deaths were observed. The mobilization and transplantation procedures were well tolerated. At 6 months post-transplant, neurological improvement or stabilization was observed in all the patients except one. Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT. Estimated event-free survival at median follow-up of 48.9 months was 80 %: 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS. Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis. At the median long-term follow-up of 62 months, 47 % of patients improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up; 45 % of patients were stable. No active, new, or enlarging lesions on magnetic resonance imaging were registered in patients without disease progression. AHSCT was accompanied by a significant improvement in patient's quality of life. Due to the fact that patient selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous, comparison with the results in the literature should be done with caution. Thus, the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population of MS patients is very favorable. The consistency of our long-term clinical and quality of life results, together with the persistence of improvement, is in favor of the efficacy and safety of this treatment approach in MS patients.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

“…Other intermediate-intensity, BEAM-modified regimens have also been used 64,65 [H3] Adverse effects AHSCT primarily targets the immune system, and immune suppression is, therefore, a necessary and expected (on-target) effect of the procedure. In an analysis of 169 patients, 79% of the early non-neurological adverse effects of AHSCT were secondary to the immunosuppression, and included neutropaenic fever, sepsis, urinary infections and viral reactivations 60 .…”

Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis

“…Of interest, Schevchenko and collegues 41 reported that 93% (28 out of 30) of progressive MS patients had no neurological progression over a 5 year follow-up after aHSCT. In our cohort (unpublished data), 43% of 122 patients treated with aHSCT had a progressive course of the disease and subgroup analyses for progressive MS demonstrated that progression-free survival was almost 60% at 5 year.…”

“…Beyond the profound effect on relapses and MRI inflammatory activity, some studies have demonstrated efficacy of aHSCT in preventing long-term neurological deterioration even in progressive MS patients 40,41 .…”

Hematopoietic Cell Transplantation for Autoimmune Diseases: A Review of History, Current State, and Future Issues

“…Other procedures of different reduced toxicity of immunoablative but not always myeloablative conditioning were published as well: mini BEAM-like, BCNU/CCNU with intermediate dose of melphalan, ±ATG or alemtuzumab, rituximab, or Cy ± thiotepa or fludarabine, etc. Some could lead to the possibility of performing this procedure in outpatient manner [43][44][45].…”