Retrospective studies
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Italy 20124949 Mancardi GL, Sormani MP, Di Gioia M, Vuolo L, Gualandi F, Amato MP, et al. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Mult Scler. 2012;18(6):835-42.
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Retrospective case series |
None |
EDSS progression free-survival |
MS treated previously with DMT with severe clinical course past year (EDSS worsening ≥ 1.0) |
74 (33 RRMS and 41 SPMS) |
BEAM + rabbit ATG |
EDSS PFS at 5y 66% for all patients RRMS EDSS PFS 5y 71% |
30% for RRMS vs 10% for SPMS |
2.7% |
95.9% |
Median 4 years (8 mo-10.5 yrs) |
Swedish 20145656 Burman J, Iacobaeus E, Svenningsson A, Lycke J, Gunnarsson M, Nilsson P, et al. Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. J Neurol Neurosurg Psychiatry. 2014;85(10):1116-21.
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Retrospective case series |
None |
Relapse free survival, MRI event free survival, EDSS PFS and DFS |
MS treated previously with DMT |
52 but analyzed 41 (40 RRMS, 5 SPMS, 2 PPMS,) |
BEAM + ATG in 41 and Cy (200 mg/kg) + ATG in 7 |
At 5y: EDSS PFS 77%; clinical relapse free survival 87%; MRI event-free survival 85% and DFS: 68% |
At 5 years, 4 patients had clinical relapse, 5 had MRI activity, 8 had EDSS progression |
Zero TRM |
100% |
Mean 4.0 years (1-9 yrs) |
Northwestern/Chicago 20155555 Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. JAMA. 2019;321(2):165.
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Retrospective case series |
None |
Time to EDSS improvement and time to EDSS worsening both at least 1.0 point |
RRMS failed DMT, with 2 or more treated relapses or 1 treated relapse with Gd lesion at a separate time/RRMS 123, SPMS 28 |
151 but 145 analyzed |
CY 200 mg/kg + alentuzumab 20 mg or rabbit ATG 6 mg/kg |
EDSS improved 50% at 2 years, 64% at 4 years Relapse-free survival was 89% at 2 years and 80% at 4 years; PFS was 92% at 2 years and 87% at 4 years and disease activity-free survival was 80% and 68% respectively |
The proportion of patients with a 1.0 or greater change in EDSS score was 10% in 19 of 112 patients with an indication of progression at 1 year and 11% in 9 of 82 for progression at 2 years; and 11% in 7 of 64 for progression at 3 years; and 8% in 3 of 36 for progression at 4 years; and 5% in 4 of 27 for progression at 5 years. |
Zero TRM |
99.3% (1 death due hypertensive cardiovascular disease) |
2,5 years (6 month-5 yrs) |
CIBMTR/EBMT Review5353 Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74(4):459.
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Retrospective registry review |
None |
PFS |
Data base of AHSCT for MS/46 RRMS, 186 SPMS, 32 PPMS, 17 PRMS |
RRMS failed DMT, with 2 or more treated relapses or 1 treated relapse with Gd lesion at a separate time/RRMS 123, SPMS 28 |
High intensity in 53/281 (18.9%); intermediate intensity in 49/281 (17.4%); low intensity in 49/281 (17.4%). |
Overall PFS was 46%; among patients with RRMs/PRMS PFS was 82% at 3 years and EDSS PFS 73% at 5 years |
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2.8% |
93% at 5 years |
Median 6.6 yrs |
Czech Republic 20103939 Krasulová E, Trneny M, Kozák T, Vacková B, Pohlreich D, Kemlink D, et al. High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Mult Scler. 2010;16(6):685-93.
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Retrospective case series |
None |
Reported efficacy of AHSCT experience in MS |
All patients treated with AHSCT 10 years 11 RRMS, 15 SPMS |
Data base of AHSCT for MS/46 RRMS, 186 SPMS, 32 PPMS, 17 PRMS |
BEAM in 26 and BEAM + ATG in 16 |
PFS at 3 years 70.8% and 29.2% at 6 years |
Median annual relapse rate within the year before ASCT was 2, while the median annual relapse rate was 0 within the first 2 years after ASCT |
Zero |
96.1% (1 death due to glioblastoma multiforme at 60 months of follow-up) |
Median 66 months (11-132) |
Spain 20175757 Casanova B, Jarque I, Gascón F, Hernández-Boluda JC, Pérez-Miralles F, de la Rubia J, et al. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis. Neurol Sci. 2017;38(7):1213-21.
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Retrospective case series |
None |
Reported toxicity and the long-term efficacy of AHSCT |
RRMS/SPMS under treatment with one of the MS-approved drugs for more than 1 year, who experienced one or more relapses in the previous year and worsening of at least 1 point in disability (EDSS) 22 RRMS, 9 SPMS |
31 |
BEAM + rabbit ATG |
100% of RRMs were free of disability at 6 months; and 60% achieving sustained disability recovery at 6 months; 22% of SPMS were free of disability at 6 months; and 10% achieving sustained disability recovery at 6 months |
32.3% (10) had at least one relapse post-AHSCT; 6 in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). 7 (22.6%) experienced progression of disability, all within SP form. |
Zero |
96.7% (1 death 13 years after transplant from aspiration pneumonia after progressing and reaching an EDSS of 9.5.) |
Median 8.4 years (2-16) |
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Single-arm prospective study
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Russia 20155858 Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA, Kartashov AV, et al. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012;40(11):892-8.
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Single arm clinical trial |
None |
Safety and efficacy (treatment response) |
All patients treated with AHSCT 6 years: EDSS 1.5-8.0, ±Gd lesions, and no treatment with interferons or immunosuppressive agents within 3 months before enrollment |
99 (43 RRMS, 56 SPMS, 18 PPMS, 3 PRMS) |
Reduced intensity conditioning regimen based on BEAM |
EFS for the whole group was 80%. In the group with RRMS, EFS was 83.3% and in the group with progressive course 75.5% 92% EDSS PFS 5 years |
16.7% at 8 years. |
Zero |
100% |
Median 48.9 months |
Northwestern/Chicago 20095959 Burt RK, Loh Y, Cohen B, Stefoski D, Stefosky D, Balabanov R, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8(3):244-53.
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Single arm clinical trial |
None |
EDSS PFS and reversal of neurologic disability |
RRMS with 2 steroid treated relapses in previous 12 month. |
21 (21 RRMS) |
Cychophosphamide + alemtuzumab/rabbit ATG |
100% EDSS PFS 3 years |
5 patients (24%) relapsed but achieved remission after further immunosuppression After a mean of 37 months (range 24-48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses |
Zero |
100% |
Mean 3.1 years (1.5-10) |
Canada 20166262 Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388(10044):576-85.
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Single arm clinical trial |
None |
MS activity-free survival (absence of clinical relapse, new MRI lesion or progression of EDSS) |
Disease activity despite 1 year of DMT. |
24 (12 RRMS, 12 SPMS) |
Cyclophosphamide/busulfan |
70% PFS 3 years |
No clinical relapse |
4.2% |
95% |
Median 6.1 year (±2.5) |
HALT-MS 2015, 20176060 Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Griffith LM, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS). JAMA Neurol. 2015;72(2):159.,6161 Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88(9):842-52.
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Single arm clinical trial |
None |
Time to treatment failure (death or MS activity) |
RRMS with failure of DMTs during the prior 18 months |
24 (24 RRMS) |
BEAM + rabbit ATG |
70% NEDA 5 years, 91% EDSS PFS |
Two participants had disease progression and died at .2.5 years and .3.5 years after AHSCT; a third participant also had disease progression at 15 months and died at 4.5 years post-HCT Of 24 patients 7 did not maintain EFS by close of follow-up by an increase in EDSS 0.5 (n = 2), clinical relapse (n = 3) or development of new MRI lesions (n = 2) |
Zero |
87.5% |
Median 4.9 year (6-12) |
Australia 20186363 Moore JJ, Massey JC, Ford CD, Khoo ML, Zaunders JJ, Hendrawan K, et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(5):514-21.
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Single arm clinical trial |
None |
EFS (NEDA) |
RRMS with at least 1 relapse or one new MRI lesion in the past year despite DMT/SPMS worsening with at least 1 MRI lesion in the past year. |
35 (20 RRMS, 15 SPMS) |
BEAM + horse ATG |
60% NEDA 3 year |
Clinical relapses occurred in 3 patients at 12, 13 and 14 months, respectively after AHSCT |
Zero |
100% |
Median 6.9 year (0.7-21.6) |
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Randomized study
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ASTIMS 20155252 Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015;84(10):981-8.
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Phase II, AHSCT vs mitoxantrone |
AHSCT vs mitoxantrone |
Cumulative number of new T2 lesion MRI 4 years after randomization |
Worsening in EDSS and one or more MRI lesion last year despite DMTs |
21 (9 to AHSCT) 7 RRMS, 13 SPMS, 1 PPMS |
BEAM + ATG |
New T2 lesion MRI: 2.5 AHSCT vs 8 mitoxantrone 4 years |
EDSS progression was 57% in AHSCT vs 48% in the mitoxantrone (p = 0.5) |
Zero |
100% |
4 years |
MIST 20185555 Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. JAMA. 2019;321(2):165.
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Phase3 AHSCT vs conventional DMT |
AHSCT vs DMT |
6-Month worsening EDSS ≥ 1.0 after one year's post-AHSCT or DMT treatment |
At least 2 clinical relapse, or one relapse in MRI lesion at different time in the last year despite DMT |
110 (55 AHSCT) 110 RRMS |
Cyclophosphamide + rabbit ATG |
At 1 year, mean EDSS improved from 3.38% to 2.36% with AHSCT and worsened from 3.31 to 3.98 with DMTs. At 1 year, mean T2 lesion volume on MRI decreased in the AHSCT, but increased in The DMT group. |
15.4% AHSCT vs 85.3% of relapse at 5 years. Disability worsening occur in 5.8% AHSCT vs 66.7% DMT group; median time to pression 24 months in the DMT. |
Zero |
100% |
Up to 5 years |