Long-term results of stem cell transplantation for MS

Fassas, Αthanasios; Kimiskidis, Vasilios Κ.; Sakellari, Ioanna; Kapinas, K.; Anagnostopoulos, Achilles; Tsimourtou, Vana; Sotirakoglou, Κyriaki; Kazis, A.

doi:10.1212/wnl.0b013e318211c537

Cited by 87 publications

(80 citation statements)

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“…The duration of stability in objective disability measures has been remarkable and appears to represent a marked change in outcome when compared to historical and concurrent MS populations. However, caution should be exercised in interpreting these results as the progression-free survival is lower in studies with longer follow-up [50,52].…”

Section: Lesson 6: Hsct Can Results In Long-term Progression-free Outcmentioning

confidence: 99%

“…Among patients having relapses until the time of HSCT, more than 85 % who received a conditioning regimen of BEAM plus ATG were free from clinical relapses in the absence of ongoing treatment with other disease-modifying agents [50,51]. Similarly, gadolinium-enhancing CNS lesions or new lesions on serial magnetic resonance imaging were uncommon [52,53]. Although randomized comparisons of different intensity conditioning regimens have not been performed, within the limitations of available information, it appears that dose-intensity influences the control of CNS inflammation.…”

Section: Lesson 4: Hsct Is More Likely To Be Effective For Ms Patientmentioning

confidence: 99%

“…However, in this instance, the improvements were sustained, but this has not always been the case. Fassas et al [52] reported that 16 patients initially had an improvement in their EDSS score after HSCT, but only 2 of 35 patients had sustained longterm improvement in EDSS at 7 years. The transplant regimen was similar in both instances, and thus the difference in outcome is conceivably due to subtle differences in patient selection, although baseline EDSS scores, age at HSCT, and time from diagnosis were similar in the 2 cohorts.…”

Section: Lesson 7: the Recovery Of Functional Ability Can Occur In Hsmentioning

confidence: 99%

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Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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Reports from more than 600 hematopoietic stem cell transplants (HSCT) have appeared in the medical literature for the last 1 and one-half decades. The patient's own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the auto-destructive immune system. The immune system is regenerated from the infused autologous hematopoietic stem cells. Increasing clinical experience has refined patient selection criteria and management in the peri-transplant period leading to a reduction in treatment-related complications. HSCT, when used to treat patients with aggressive highly active multiple sclerosis, can reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients, in the absence of chronic treatment with disease-modifying agents. The top 10 lessons learned from the growing experience using HSCT for the treatment of multiple sclerosis are discussed.Keywords Hematopoietic stem cell transplantation . Multiple sclerosis . Autoimmunity . Immune ablation There are published reports of more than 600 bone marrowbased transplants performed primarily for the treatment of multiple sclerosis (MS). This review will focus on why and how the hematopoietic stem cell transplantation (HSCT) procedure is used and discuss some of the lessons that can be gleaned from the experience of using HSCT to treat MS.MS is an organ-specific autoimmune disease that results in exclusive central nervous system (CNS) demyelination and axonal damage. Early on, multifocal localized pockets of inflammation lead to transient neurologic dysfunction manifesting as a series of relapses followed by remissions, usually with complete recovery owing to adequate CNS repair. However, as the damage accumulates, repair becomes inadequate and leads to incomplete resolution of disability, culminating in a neurodegenerative process amid a sea of smoldering and changing inflammation. This is probably the underlying state for the clinical stage of secondary progressive MS (SP-MS), a phase characterized by relentless and progressive accumulation of neurological disability with dwindling evidence of discrete relapses [1].Targeting inflammation with interferon-β, glatiramer acetate, natalizumab, fingolimod, and other immune-modulating agents reduces the frequency of relapses, but the impact on delaying the onset, preventing or slowing the tempo of SP-MS remains uncertain [2][3][4]. Several other drugs are in late stage clinical trials and may provide new alternatives for some patients with relapsing-remitting MS (RR-MS). However, despite these therapeutic advances, a subset of patients seem refractory and rapidly develop severe neurological impairment, whereas other patients may have a slower progression of illness that ultimately results in marked functional disabilities. Only a single agent, mitoxantrone, has been shown to temporarily halt or slow the tempo of SP-MS [5,6], but even then, this occurs only in SP-MS patients who have highly act...

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Section: Lesson 6: Hsct Can Results In Long-term Progression-free Outcmentioning

confidence: 99%

Section: Lesson 4: Hsct Is More Likely To Be Effective For Ms Patientmentioning

confidence: 99%

Section: Lesson 7: the Recovery Of Functional Ability Can Occur In Hsmentioning

confidence: 99%

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Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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“…Besides isolated reports of AHSCT being used for early treatment of highly aggressive relapsing inflammatory forms of MS 43,44 , the initial clinical studies of AHSCT in MS were conducted almost exclusively in patients with high levels of disability and progressive disease [45][46][47][48] as randomized controlled studies with these patients would be unethical.…”

Section: [H2] Efficacymentioning

confidence: 99%

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

et al. 2017

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Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ~20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4–5 years in 70–80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs

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“…Between the initial pilot study in 1995 [32] and 2011, over 700 people with MS have undergone autologous HSCT [33]. Approximately 70% of treated patients remain free of disease progression 3 years post-transplant based on expanded disability status scale (EDSS) scores [34].…”

Section: Haematopoietic Stem Cell Transplantation For Autoimmune Diseasementioning

confidence: 99%

Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: The future for therapy of autoimmune disease?

Coleman

Steptoe

2012

Autoimmunity Reviews

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Long-term results of stem cell transplantation for MS

Abstract: This study provides Class IV evidence that HSCT results in PFS rates of 25%. PFS rate was significantly better in patients with active MRI lesions; HSCT also resulted in a significant reduction in the number and volume of gadolinium-enhancing lesions on MRI.

Cited by 87 publications

References 10 publications

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: The future for therapy of autoimmune disease?

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