Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)

Bone Marrow Transplantation, Journal Year: 2019, Volume and Issue: 55(2), P. 283 - 306

Published: Sept. 26, 2019

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) other immune-mediated neurological diseases provide recommendations for patient selection, transplant technique, follow-up future development. The major focus is on autologous HSCT (aHSCT), used MS over two decades currently fastest growing indication this treatment Europe, with increasing evidence to support its use highly active relapsing remitting failing respond disease modifying therapies. aHSCT may have a potential role progressive forms significant inflammatory component diseases, including chronic demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis stiff person syndrome. Allogeneic should only be considered where risks are justified. Compared immunomodulatory treatments, associated greater short-term requires close interspeciality collaboration between physicians neurologists special interest these conditions before, during after accredited centres. Other experimental therapies developmental patients treated trials.

Language: Английский

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Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation

Biology of Blood and Marrow Transplantation, Journal Year: 2019, Volume and Issue: 25(5), P. 845 - 854

Published: Feb. 19, 2019

Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, demyelinating and degenerative disease of the central nervous system. Approved disease-modifying therapies may be incompletely effective in some patients with highly active relapsing high risk disability. The use immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated retrospective studies, clinical trials, meta-analyses/systematic reviews as an approach to address this unmet need. On behalf American Society for Blood Bone Marrow Transplantation (ASBMT), panel experts AHCT MS convened review available evidence make recommendations on indication AHCT. A recent literature identified 8 3 reviews. In aggregate, these studies indicate that efficacious safe treatment forms prevent relapse, magnetic resonance imaging-detectable lesion activity, worsening disability reverse without unexpected adverse events. Based evidence, ASBMT recommends treatment-refractory future considered "standard care, available" Collaboration neurologists expertise treating physicians experience performing autoimmune crucial ensuring appropriate patient selection optimizing procedures improve outcomes. centers United States Canada are strongly encouraged report baseline outcomes data receiving multiple Center International Transplant Research.

Language: Английский

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Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm

Current Opinion in Neurology, Journal Year: 2019, Volume and Issue: 32(3), P. 365 - 377

Published: April 15, 2019

To critically assess the current landscape of disease-modifying agents for multiple sclerosis (MS). Treatment algorithms will be discussed and studies new in late development or recently approved are analyzed terms their impact on treatment strategies.A real-world study from Wales suggests that early initiation highly effective therapy may provide more benefit an escalation approach relapsing MS. A MSBase dataset found evidence with therapies decreased risk developing secondary progressive Ocrelizumab is efficacious MS a group patients primary Another CD20 directed mAb, ofatumumab, phase 3. large examining extended interval dosing natalizumab attempt to decrease multifocal leukoencephalopathy underway. Cladribine alemtuzumab work by immune reconstitution. Siponimod was United States Federal Drug Administration active Other S1P receptor modulators being studied 3 trials received FDA approval as Autologous hematopoetic stem-cell transplantation option treatment-refractory MS.Development continues successful. need take developments into account.

Language: Английский

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Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Neurology, Journal Year: 2021, Volume and Issue: 96(8)

Published: Jan. 20, 2021

To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after a large cohort of patients MS.To be included, minimum dataset (consisting age, MS phenotype, Expanded Disability Status Scale [EDSS] score at baseline, information on technology, and least 1 follow-up visit transplantation) was required.Two hundred ten were included (relapsing-remitting [RR] 122 [58%]). Median baseline EDSS 6 (1-9); mean 6.2 (±5.0) years. Among RRMS, disability worsening-free survival (95% confidence interval [CI]) 85.5% (76.9%-94.1%) 5 years 71.3% (57.8%-84.8%) 10 In progressive MS, 71.0% (59.4%-82.6%) 57.2% (41.8%-72.7%) years, respectively. significantly reduced aHSCT (p = 0.001; change per year -0.09 [95% CI -0.15% -0.04%]). use BCNU+Etoposide+Ara-C+Melphalan (BEAM) + anti-thymocyte globulin (ATG) conditioning protocol independently associated risk no evidence activity 3 failure (hazard ratio 0.27 0.14-0.50], p < 0.001). Three died within 100 days from (1.4%); deaths occurred transplanted 2007.aHSCT prevents worsening majority induces improvement RRMS. The BEAM ATG more pronounced suppression clinical relapses MRI inflammatory activity.This study provides Class IV that for most patients.

Language: Английский

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Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 1, 2022

Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which mediated by an abnormal immune response coordinated T and B cells resulting in areas of inflammation, demyelination, axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but ineffective many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment patients with highly active disease, achieving long-term clinical remission most. The rationale intervention eradicate autoreactive lympho-ablative regimens restore tolerance. Immunological studies have demonstrated that autologous HSCT induces renewal TCR repertoires, resurgence regulatory cells, depletion proinflammatory subsets, suggesting “resetting” immunological memory. Although our understanding effects progressed, further work required characterize mechanisms underlie efficacy. Considering memory disease-promoting stem-like multipotent progenitors involved self-regeneration effector investigating reconstitution compartment subsets following could elucidate those mechanisms. Since all subjects need be optimally protected from vaccine-preventable diseases (including COVID-19), there ensure vaccination undergoing effective safe. Additionally, study HSCT-treated means evaluating responses distinguish broad immunosuppression resetting.

Language: Английский

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Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis

JAMA Neurology, Journal Year: 2023, Volume and Issue: 80(7), P. 702 - 702

Published: May 15, 2023

Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).

Language: Английский

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Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 901 - 912

Published: March 21, 2024

Language: Английский

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Effectiveness of autologous haematopoietic stem cell transplantation versus natalizumab in progressive multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2024, Volume and Issue: 95(8), P. 775 - 783

Published: March 27, 2024

Background Natalizumab was not shown to modify disability in progressive multiple sclerosis (MS). This matched observational study compared the effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) with natalizumab MS. Methods Patients primary/secondary MS from seven AHSCT centres and MSBase registry, treated or natalizumab, were on a propensity score derived sex, age, Expanded Disability Status Scale (EDSS), number relapses 12/24 months before baseline, time onset, most effective prior therapy country. The pairwise-censored groups hazards 6-month confirmed EDSS worsening improvement, annualised relapse rates (ARRs), using Andersen-Gill proportional models conditional negative binomial model. Results 39 patients (37 secondary MS, mean age 37 years, 5.7, 28% recent progression, ARR 0.54 during preceding year) 65 natalizumab. found no evidence for difference (HR 1.49, 95% CI 0.70 3.14) improvement 1.50, 0.22 10.29) between over up 4 years. activity also similar while (ARR: mean±SD 0.08±0.28 vs 0.08±0.25; HR 1.05, 0.39 2.82). In group, 3 experienced febrile neutropenia mobilisation, 9 serum sickness, 6 required intensive care unit admission 36 complications after discharge. No treatment-related deaths reported. Conclusion does support use control advanced low activity.

Language: Английский

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Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis

JAMA Neurology, Journal Year: 2020, Volume and Issue: 78(2), P. 241 - 241

Published: Oct. 26, 2020

Importance

Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration–approved disease-modifying therapies, some patients do not respond adequately others may have very early aggressive disease that prompts consideration alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee Multiple Sclerosis Society reviewed literature on AHSCT purpose making recommendations about its use based current knowledge, as well pointing out areas controversy issues requiring further research.

Observations

Studies repeatedly demonstrated high efficacy a durable outcome people with relapsing sclerosis. Recent studies shown considerable improvement safety procedure, much lower mortality rates than were reported earlier. Consensus is emerging characteristics best candidates procedure. Questions remain ideal protocol, particularly conditioning regimen to be used kill immune cells. Larger randomized clinical trials are needed address question whether advantages over most efficacious agents currently available. One such trial (Best Available Therapy Versus Hematopoietic Stem Cell Transplant [BEAT-MS) progress.

Conclusions Relevance

believes useful treatment option who demonstrate substantial breakthrough activity (ie, new inflammatory central nervous system lesions and/or relapses) despite high-efficacy therapy or contraindications therapies. likely younger 50 years shorter durations (<10 years). procedure should only performed at centers experience expertise. Ideally, recipients entered into single database, research establish mobilization immune-conditioning regimens.

Language: Английский

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Immunological consequences of “immune reconstitution therapy” in multiple sclerosis: A systematic review

Autoimmunity Reviews, Journal Year: 2020, Volume and Issue: 19(4), P. 102492 - 102492

Published: Feb. 13, 2020

Language: Английский

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