title: 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.
authors.affiliation: Pirogov National Medical Surgical Center, 70 Nizhnaya Pervomaiskaya str., 105 207, Moscow, Russia.
authors.forename: Jury L
authors.initials: JL
authors.lastname: Shevchenko
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Kuznetsov
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Ionova
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Melnichenko
authors.forename: Denis A
authors.initials: DA
authors.lastname: Fedorenko
authors.forename: Kira A
authors.initials: KA
authors.lastname: Kurbatova
authors.forename: Gary I
authors.initials: GI
authors.lastname: Gorodokin
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Novik
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000523:psychology / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D010358:Patient Participation / Q000523:psychology / Q000639:trends*; D010819:Physician's Role / Q000523:psychology; D011446:Prospective Studies; D011788:Quality of Life / Q000523:psychology; D013997:Time Factors; D019172:Transplantation Conditioning / Q000523:psychology / Q000639:trends*; D014182:Transplantation, Autologous / Q000523:psychology / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult