Intensive immunosuppression followed by autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis

Autologous hematopoietic stem cell transplantation (AHSCT) to treat multiple sclerosis (MS) has mostly been used in devastating cases as the last option to stop further neurological deterioration. However, evidence from several retrospective clinical trials indicates that young, less disabled patients with highly inflammatory active MS are the most likely to benefit from AHSCT, and after moving from high-intensity to nonmyeloablative procedures the tolerability of AHSCT has increased and its associated risk and mortality have declined considerably. Recent meta-analyses and randomized clinical trials show that AHSCT is more effective than currently approved disease-modifying therapies (DMTs), with suppression of disease activity in 70–90% of patients and long-term cessation of disease activity in two-thirds of treated patients. The rationale for AHSCT is to eliminate autoimmunity and achieve immune resetting by intense immunosuppression followed by infusion of autologous hematopoietic stem cells. Similar effects on the immune system have been suggested for cladribine and alemtuzumab treatment and, together with AHSCT, they constitute the induction or immune-reconstitution therapies for MS. Although, further randomized controlled trials of AHSCT for MS are needed, it has become clear that improved patient selection and lower intensity conditioning regimens have reduced AHSCT associated risks and mortality and strengthened the position of AHSCT among other DMTs. Do we have enough experience and scientific support for AHSCT in MS to move from an exclusive treatment for aggressive, treatment-resistant MS and acquire broader indications, similar to other effective DMTs?

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Nine-year follow up after hematopoietic stem cell transplantation in five multiple sclerosis patients

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190097 ◽

2019 ◽

Vol 77 (8) ◽

pp. 531-535 ◽

Cited By ~ 1

Author(s):

Elizabeth R. Comini-Frota ◽

Bruna C. C. Marques ◽

Caio Torres ◽

Karoline M. S. Cohen ◽

Eduardo Carvalho Miranda

Keyword(s):

Multiple Sclerosis ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Disease Activity ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Disease Onset ◽

Hematopoietic Stem ◽

Relapsing Remitting

ABSTRACT Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Its treatment has focused on inflammation control as early as possible to avoid disability. Autologous hematopoietic stem cell transplantation (AHSCT) has been used for treating MS since 1996, with recent decisive results regarding benefits in long-term efficacy. Five patients followed up at an MS center in Belo Horizonte, Brazil, who had relapsing-remitting MS with high disease activity, underwent AHSCT between 2009 and 2011. They were evaluated clinically, with magnetic resonance imaging, and by the EDSS every six months after transplantation, up to July 2018. The patients were four women and one man, with ages ranging from 25-50 years, and time since disease onset ranging from 4-17 years at the time of the procedure. Four patients improved, one patient was stabilized, and all patients were free of disease activity after 5-9 years. Through improving patient selection and decreasing the time from disease onset, AHSCT could stop epitope spreading and disease progression. Despite multiple other therapeutic choices being approved for relapsing-remitting MS, AHSCT continues to be a treatment to consider for aggressive MS disease.

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Randomized clinical trials for hematopoietic stem cell transplantation: lessons to be learned from the European experience

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1705230 ◽

2005 ◽

Vol 37 (2) ◽

pp. 219-221 ◽

Cited By ~ 3

Author(s):

S S Kuthiala ◽

G H Lyman ◽

O F Ballester

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Randomized Clinical Trials ◽

Hematopoietic Stem ◽

European Experience

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Signal mass change as a marker of brain tissue loss in multiple sclerosis patients following immunoablative therapy and autologous hematopoietic stem cell transplantation

10.26226/morressier.5b719e465aff74008ae4c9f9 ◽

2018 ◽

Author(s):

Hyunwoo Lee ◽

Robert A. Brown ◽

Douglas L. Arnold

Keyword(s):

Multiple Sclerosis ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Brain Tissue ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Tissue Loss ◽

Hematopoietic Stem ◽

Multiple Sclerosis Patients

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A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1711 ◽

2020 ◽

Author(s):

Benjamin W Teh ◽

Vivian K Y Leung ◽

Francesca L Mordant ◽

Sheena G Sullivan ◽

Trish Joyce ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Influenza Vaccination ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Influenza B ◽

High Dose ◽

Hematopoietic Stem

Abstract Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. Methods A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2–14.9; P = .02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Clinical Trials Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.

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