Autologous Hematopoietic Cell Transplantation in Multiple Sclerosis: Changing Paradigms in the Era of Novel Agents

Gavriilaki, Maria; Sakellari, Ioanna; Kimiskidis, Vasilios Κ.; Anagnostopoulos, Achilles

doi:10.1155/2019/5840286

Cited by 14 publications

(11 citation statements)

References 84 publications

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“…The main reason for using intermediate intensity regimen instead of high intensity regimen was to avoid transplant related mortality. www.nature.com/scientificreports/ The primary goal of AHSCT is to suppress the active disease and to prevent further disability progression 5,9,10 . The main result in the terms of efficacy in our study was the dramatic reduction in the relapses and annualized relapse rate in the 2 years after AHSCT and the reduction of disability progression, with 84.6% of patients improving their disability score after AHSCT at month 6 and 76.9%-at month 12.…”

Section: Discussionmentioning

confidence: 99%

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Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

Giedraitienė

Kizlaitienė

Pečeliūnas

et al. 2020

Sci Rep

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The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed.

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Section: Discussionmentioning

confidence: 99%

“…During the last 25 years, severe autoimmune diseases including MS have been treated with immunosuppression and autologous hematopoietic stem cell transplantation (AHSCT) 5 , 6 . It enables to remove disease-causing immune cells and to reset the immune system 2 .…”

Section: Introductionmentioning

confidence: 99%

Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

Giedraitienė

Kizlaitienė

Pečeliūnas

et al. 2020

Sci Rep

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“…In MS, more than 3000 autologous transplants have been performed with excellent outcomes obtained for 5-year disease remission [19]. The mechanism by which transplant contributes to the stabilization of disease in neuroinflammatory conditions such as MS and cALD is not clear but likely involves immune modulatory aspects (driven by chemotherapy and infused hematopoietic stem cells) associated with the transplant process.…”

Section: Discussionmentioning

confidence: 99%

Volume of Gadolinium Enhancement and Successful Repair of the Blood-Brain Barrier in Cerebral Adrenoleukodystrophy

Lund

Orchard

et al. 2020

Biology of Blood and Marrow Transplantation

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Up to 40% of boys with adrenoleukodystrophy develop a severe central nervous system demyelinating form (cALD) characterized by white matter changes and gadolinium enhancement on magnetic resonance imaging (MRI). Hematopoietic cell transplant (HCT) is the only proven means to attenuate cALD progression. The elimination of active neuroinflammation is indicated radiographically by the resolution of gadolinium (Gd) enhancement and correlates to speed of donor neutrophil recovery. We analyzed 66 boys with cALD undergoing HCT for biomarkers correlating with early (30 days post-HCT) Gd signal resolution. We found that log Gd volume (cm 3) on pre-HCT MRI strongly positively correlated to day 30 Gd resolution (P = .0003) with smaller volume correlating to higher proportion resolved, as was the baseline gadolinium intensity score (P = .04), plasma chitotriosidase activity (P = .04), and faster absolute neutrophil count recovery (P = .03). In multivariate analysis, log Gd volume remained superior in determining which patients would have Gd signal resolution by 30 days post-HCT (P = .016). A final analysis indicated that early Gd resolution also correlated with less neurologic progression from baseline to 1 year following HCT (P = .006). MRI Gd volume may serve as a contributing biomarker to better delineate outcomes and an important metric in comparing therapies in the treatment of cALD.

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“…Notably, whether the transplanted HSCs only provide means to overcome the cytopenia and toxicity caused by the immunosuppressive conditioning regimen, or whether there is a distinct transplantassociated anti-inflammatory effect, remains a matter of debate (Miller et al, 2021). Nonetheless, HSCs have little regenerative impact on the CNS as HSCs lack the ability to differentiate into neurons, astrocytes or oligodendrocytes (Gavriilaki et al, 2019). Thus, HSC transplantation is primarily efficacious for the treatment of clinical forms of MS with high inflammatory activity (i.e., RRMS or active PMS with clinical and/or radiological evidence of inflammation), but has limited efficiency in the case of inactive PMS, failing to address the degenerative component of the disease (Muraro et al, 2017a;Gavriilaki et al, 2019).…”

Section: Hematopoietic Stem Cell Sourcesmentioning

confidence: 99%

Stem Cell Therapies for Progressive Multiple Sclerosis

Smith¹,

Nicaise

Ionescu

et al. 2021

Front. Cell Dev. Biol.

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal degeneration. MS patients typically present with a relapsing-remitting (RR) disease course, manifesting as sporadic attacks of neurological symptoms including ataxia, fatigue, and sensory impairment. While there are several effective disease-modifying therapies able to address the inflammatory relapses associated with RRMS, most patients will inevitably advance to a progressive disease course marked by a gradual and irreversible accrual of disabilities. Therapeutic intervention in progressive MS (PMS) suffers from a lack of well-characterized biological targets and, hence, a dearth of successful drugs. The few medications approved for the treatment of PMS are typically limited in their efficacy to active forms of the disease, have little impact on slowing degeneration, and fail to promote repair. In looking to address these unmet needs, the multifactorial therapeutic benefits of stem cell therapies are particularly compelling. Ostensibly providing neurotrophic support, immunomodulation and cell replacement, stem cell transplantation holds substantial promise in combatting the complex pathology of chronic neuroinflammation. Herein, we explore the current state of preclinical and clinical evidence supporting the use of stem cells in treating PMS and we discuss prospective hurdles impeding their translation into revolutionary regenerative medicines.

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Autologous Hematopoietic Cell Transplantation in Multiple Sclerosis: Changing Paradigms in the Era of Novel Agents

Cited by 14 publications

References 84 publications

Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

Volume of Gadolinium Enhancement and Successful Repair of the Blood-Brain Barrier in Cerebral Adrenoleukodystrophy

Stem Cell Therapies for Progressive Multiple Sclerosis

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