Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation

Fagius, Jan; Lundgren, Jakob; Öberg, Gunnar

doi:10.1177/1352458508096875

Cited by 73 publications

(41 citation statements)

References 28 publications

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“…Younger and less disabled patients who have been recently diagnosed are more likely to have active neuroinflammation and are more likely to benefit from HSCT. Some patients with very advanced functional impairment due to the brisk neuroinflammation associated with malignant MS have had (at times) dramatic responses to transplantation [46][47][48], supporting the idea that it is neuropathology rather than disability that determines the outcome to HSCT. Less intensive regimens, such as cyclophosphamide with ATG, have resulted in the reduction of signs of CNS inflammation; however, some of these patients breakthrough and experience ongoing relapses after HSCT.…”

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

confidence: 96%

“…More dramatic improvements have been reported for patients with malignant MS who have undergone HSCT. With follow-up extending to 4 years, the EDSS score dropped from a mean of 6.8 (range, 3.5-9.0) prior to HSCT to a mean of 3.1 (range, 0-6.0) among 13 patients with disability who progressed rapidly after diagnosis [46][47][48]. The mechanism of recovery has not been investigated and it is not clear whether the HSCT graft contributes directly or indirectly to the recovery.…”

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

confidence: 96%

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

confidence: 99%

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%

“…In rare cases of extremely aggressive MS that causes a high degree of disability in a matter of weeks, AHSCT can be considered as a potentially lifesaving treatment and has been used successfully in this context 43,44,81,82 . Besides these situations, however, patients with an EDSS score <6 (ambulatory without aid) are the most appropriate candidates for AHSCT and, on the basis of published evidence 60,57 and our clinical experience, we suggest that patients with established EDSS scores ≥7 are at high risk of complications and treatment failure, so are not appropriate candidates for AHSCT.…”

Section: [H3] Neurological Disabilitymentioning

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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“…11,21 Many terms have been proposed for this phenomenon-malignant MS, aggressive MS, catastrophic MS, fulminant MS-with a seemingly equal number of definitions, both qualitative and quantitative. [22][23][24] The lack of consensus likely stems from the difficulty of applying a uniform definition of severe MS to patients in different stages of the disease, as can be illustrated with the following examples. One patient is a woman who is wheelchair-bound, but able to transfer, after 15 years with MS; the other patient is a young man who requires a cane 2 years after MS onset.…”

Section: Herbert's Definition Of Aggressive Msmentioning

confidence: 99%

Severity Grading in Multiple Sclerosis

Charlson¹,

Herbert²,

Kister³

2016

International Journal of MS Care

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CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Appropriately apply information learned in this activity to assign a severity grade to MS patients Recognize the limitations of the severity grading scheme and be able to address those limitations in both treating and educating patients Accreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Practitioner Alternatives (NPA) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPA designates this enduring material for 1.0 Continuing Nursing Education credit (none of these credits are in the area of pharmacology). Disclosures: Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has disclosed no relevant financial relationships. Robert Charlson, MD, has served on an advisory board for Teva Pharmaceuticals. Joshua Herbert, BA, has disclosed no relevant financial relationships. Ilya Kister, MD, has served as a consultant for Biogen Idec and Genentech. Dr. Kister has also performed contracted research for Bayer, Genzyme, and Biogen Idec. Laurie Scudder, DNP, NP, has served as Nurse Planner for this activity. She has disclosed no relevant financial relationships. The anonymous peer reviewers for the IJMSC have disclosed no relevant financial relationships. The staff at the CMSC, NPA, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Method of Participation: Release Date: October 1, 2016 Valid for Credit Through: October 1, 2017 In order to receive CME/CNE credit, participants must:Review the CME/CNE information, including learning objectives and author disclosures.Study the educational content.Complete the post-test and evaluation, which are available at http://www.cmscscholar.org. Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This CME/CNE activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC, NPA, and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC, NPA, or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

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Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation

Abstract: This small series of patients with "malignant" relapsing-remitting MS suggests HSCT to be an effective treatment option for this relatively rare disease course. It further suggests that future criteria for HSCT in MS should be close to the present ones.

Cited by 73 publications

References 28 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

Severity Grading in Multiple Sclerosis

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