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Haematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis: Recent Advances

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS (2023)

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Article Clinical Neurology

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis

Giacomo Boffa et al.

Summary: This study compared the effects of autologous hematopoietic stem cell transplantation (AHSCT) with other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active secondary progressive multiple sclerosis (SPMS). The results showed that AHSCT was associated with a slower disability progression and a higher likelihood of disability improvement compared to standard immunotherapy.

NEUROLOGY (2023)

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Article Multidisciplinary Sciences

Anti-Mullerian hormone and pregnancy after autologous hematopoietic stem cell transplantation for multiple sclerosis

Lida Zafeiri et al.

Summary: This study investigated the relationship between AMH levels and age and reproductive potential in MS patients treated with AHSCT. The results showed that although AMH concentration significantly decreased after AHSCT, six patients successfully conceived despite low concentrations, suggesting that high-dose cyclophosphamide treatment may not negatively impact fertility.

PLOS ONE (2023)

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Article Clinical Neurology

Autologous haematopoietic stem cell transplantation versus low-dose immunosuppression in secondary-progressive multiple sclerosis

Alice Mariottini et al.

Summary: The study demonstrates that for patients with secondary-progressive multiple sclerosis (SP-MS), AHSCT is more effective than cyclophosphamide (Cy) in reducing relapse activity, but there is no significant difference between the two in terms of disability progression. AHSCT is beneficial for reducing relapses, but disability progression in SP-MS is more likely driven by noninflammatory neurodegeneration.

EUROPEAN JOURNAL OF NEUROLOGY (2022)

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Article Clinical Neurology

Real-world application of autologous hematopoietic stem cell transplantation in 507 patients with multiple sclerosis

Richard K. Burt et al.

Summary: This study investigated the real-world outcomes of non-myeloablative autologous HSCT in patients with RRMS and SPMS. The results showed a high 5-year survival rate for the majority of patients, with significant improvement in EDSS scores for RRMS patients over time, while HSCT was found to be of less benefit for newly diagnosed SPMS patients.

JOURNAL OF NEUROLOGY (2022)

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Review Immunology

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

Maria Teresa Cencioni et al.

Summary: Multiple sclerosis (MS) is a central nervous system disorder characterized by inflammation, demyelination, and axonal loss. Autologous hematopoietic stem cell transplantation (HSCT) has shown promising results in achieving long-term clinical remission in highly active MS patients by eradicating autoreactive cells and restoring immune tolerance. Further research is needed to understand the mechanisms behind the effectiveness of HSCT and to study the reconstitution of immunological memory following the treatment. Additionally, evaluating the efficacy and safety of vaccination in HSCT-treated subjects can provide insights into immune responses and distinguish between broad immunosuppression and immune resetting.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Clinical Neurology

Intermediate-Intensity Autologous Hematopoietic Stem Cell Transplantation Reduces Serum Neurofilament Light Chains and Brain Atrophy in Aggressive Multiple Sclerosis

Alice Mariottini et al.

Summary: The study found that intermediate-intensity AHSCT significantly reduced neurofilament light chain concentration in aggressive MS patients, reducing axonal damage occurrence. There was no clear association between sNfL levels and treatment response, indicating sNfL's sensitivity to inflammatory activity.

FRONTIERS IN NEUROLOGY (2022)

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Article Clinical Neurology

Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT

Silje Agnethe Stokke Kvistad et al.

Summary: The impact of previous long-lasting disease-modifying treatments on the safety and efficacy of autologous haematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS) was explored in this study. The results showed that previous treatments did not affect the treatment-related complications and long-term outcome of AHSCT.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2022)

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Article Clinical Neurology

Biomarkers of demyelination and axonal damage are decreased after autologous hematopoietic stem cell transplantation for multiple sclerosis

Christina Zjukovskaja et al.

Summary: This study found that in most patients, biomarkers of demyelination and axonal damage reached normal values within five years from treatment with aHSCT.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2022)

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Article Biochemistry & Molecular Biology

Dynamics of Inflammatory and Neurodegenerative Biomarkers after Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Josefine Ruder et al.

Summary: Autologous hematopoietic stem cell transplantation (aHSCT) is an effective treatment for multiple sclerosis (MS), which normalizes pathological processes and enhances beneficial processes. Biomarker analysis of MS patients undergoing aHSCT showed that serum levels of CXCL10, NfL, and GFAP significantly increased one month after transplantation, but returned to normal after one to two years. Levels of GFAP in cerebrospinal fluid (CSF) increased 24 months after aHSCT, indicating sustained astroglia activation. Other CSF markers remained relatively stable.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Cell Biology

Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis

Josefine Ruder et al.

Summary: Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment for multiple sclerosis (MS), renewing adaptive immune cells. The dynamics of T cells after aHSCT were examined in this study. The results showed that naive T cells were barely detectable early after aHSCT, while effect or memory (EM) T cells quickly reconstituted. EM CD4(+) T cells early after aHSCT exhibited shorter telomeres and higher expression of senescence and exhaustion markers. The T cell receptor (TCR) repertoire overlap between early post-aHSCT EM CD4(+) T cells and pre-aHSCT declined over time, indicating the renewal of the T cell repertoire by nascent T cells. The reactivity of HLA-DR-associated EM CD4(+) T cells towards MS-related antigens decreased after aHSCT, while reactivity towards Epstein-Barr virus (EBV) increased.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Multidisciplinary Sciences

Impact of autologous HSCT on the quality of life and fatigue in patients with relapsing multiple sclerosis

N. Giedraitiene et al.

Summary: This study aimed to evaluate the effects of AHSCT on quality of life, fatigue, anxiety, and depression in patients with multiple sclerosis. The results showed that AHSCT could improve the quality of life and reduce fatigue symptoms in these patients, with the improvement in quality of life occurring earlier than in fatigue.

SCIENTIFIC REPORTS (2022)

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Article Health Care Sciences & Services

Impact of Immunoablation and Autologous Hematopoietic Stem Cell Transplantation on Treatment Cost of Multiple Sclerosis: Real-World Nationwide Study

Katarzyna Orlewska et al.

Summary: By analyzing data from 105 patients undergoing AHSCT treatment, it was found that AHSCT treatment can significantly reduce the treatment costs of patients with multiple sclerosis, and from the perspective of public payers, the costs of AHSCT and post-treatment can be recovered in a short period of time.

VALUE IN HEALTH REGIONAL ISSUES (2021)

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Review Clinical Neurology

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis Recommendations of the National Multiple Sclerosis Society

Aaron E. Miller et al.

Summary: AHSCT has shown high efficacy and safety in treating relapsing MS patients, with ongoing research needed to compare its advantages with current disease-modifying therapies. Ideal candidates are likely to be younger than 50 years old with disease duration of less than 10 years. Additional studies are needed to establish optimal cell mobilization and immune-conditioning regimens.

JAMA NEUROLOGY (2021)

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Article Clinical Neurology

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

Giacomo Boffa et al.

Summary: The study analyzed the long-term outcomes of autologous hematopoietic stem cell transplantation in patients with multiple sclerosis, showing that it prevents disability worsening in most patients and induces durable improvement in disability in patients with relapsing-remitting MS. The BEAM+ ATG conditioning protocol was found to be associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity.

NEUROLOGY (2021)

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Article Clinical Neurology

Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis

J. Das et al.

Summary: The study demonstrates that AHSCT as a first-line DMT for patients with 'aggressive' MS is safe and effective in inducing rapid and sustained remission. Patients showed improvement in EDSS score and no further relapses were reported during follow-up.

MULTIPLE SCLEROSIS JOURNAL (2021)

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Article Clinical Neurology

Menstrual cycle resumption and female fertility after autologous hematopoietic stem cell transplantation for multiple sclerosis

Claudia Massarotti et al.

Summary: In a multi-center cohort of MS women, 70% of women resumed menstruation after aHSCT with a mean time of 6.8 months. Older age and previous pulsed cyclophosphamide use were independently associated with lower probability of menstrual recovery.

MULTIPLE SCLEROSIS JOURNAL (2021)

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Review Biophysics

New autoimmune diseases after autologous hematopoietic stem cell transplantation for multiple sclerosis

Richard K. Burt et al.

Summary: Secondary autoimmune diseases (2ndADs) occur in 5-14% of allogeneic and autologous hematopoietic stem cell transplants, with Alemtuzumab identified as a potential risk factor. The imbalance between B and T lineage regeneration early after HSCT may contribute to the pathogenesis of 2ndADs.

BONE MARROW TRANSPLANTATION (2021)

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Article Immunology

NK Cells and Innate-Like T Cells After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Josefine Ruder et al.

Summary: It was found that after autologous hematopoietic stem cell transplantation, the relative frequency and absolute numbers of CD56(bright) NK cells in patients with multiple sclerosis increased, while all studied innate-like T cell populations decreased.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Clinical Neurology

Pregnancy post autologous stem cell transplant with BEAM conditioning for multiple sclerosis

Sophie Chatterton et al.

Summary: After AHSCT for MS, both male and female patients may experience pregnancy, and should receive full counseling on fertility and contraception before treatment.

MULTIPLE SCLEROSIS JOURNAL (2021)

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Article Clinical Neurology

aHSCT is superior to alemtuzumab in maintaining NEDA and improving cognition in multiple sclerosis

Vivien Haeussler et al.

Summary: This study compared the outcomes of patients with highly active multiple sclerosis treated with either autologous hematopoietic stem cell transplantation (aHSCT) or alemtuzumab. The results showed that more patients in the aHSCT group maintained no evidence of disease activity and experienced improvement in EDSS compared to those in the alemtuzumab group.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2021)

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Review Clinical Neurology

B cells in multiple sclerosis - from targeted depletion to immune reconstitution therapies

Maria T. Cencioni et al.

Summary: This Review discusses the roles of B cells in multiple sclerosis, highlighting the involvement of B cells in disease pathogenesis and the potential mechanisms underlying the abnormalities in B cell function in MS.

NATURE REVIEWS NEUROLOGY (2021)

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Article Clinical Neurology

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis A Real-world Case Series

Richard S. Nicholas et al.

Summary: The study found that PwMS treated with AHSCT had a MS relapse-free survival rate of 93% at 2 years and 87% at 4 years, with no new MRI lesions detected in 90% of participants at 2 years and 85% at 4 years. The progression-free survival rate of EDSS score was 75% at 2 years and 65% at 4 years. EBV reactivation and monoclonal paraproteinemia were associated with worse progression-free survival.

NEUROLOGY (2021)

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Article Clinical Neurology

Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis

Hyunwoo Lee et al.

Summary: In RRMS patients who received BEAM-based HDIT/HCT, short-term wholebrain, grey-matter, and white-matter volume loss was observed, with rates slowing down in the long term. Patients with gadolinium-enhancing lesions at baseline showed higher GM and WB volume loss rates at 1 year follow-up, while WM volume loss rates were not significantly different. Maintaining event-free survival did not impact the rates of BVL.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2021)

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Article Clinical Neurology

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis

Richard S. Nicholas et al.

Summary: The study aimed to examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. Results showed that survival free of MS relapses, MRI new lesions, and worsening of EDSS score were relatively high in this cohort, but with some risks.

NEUROLOGY (2021)

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Article Clinical Neurology

Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study

Christina Zhukovsky et al.

Summary: In this study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity', while adverse events were more frequent in the first 100 days. On the other hand, treatment with ALZ had fewer adverse events initially but became more common later on.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2021)

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Article Clinical Neurology

Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis

Peter Alping et al.

Summary: This study compares the safety outcomes of different induction therapies for multiple sclerosis patients. It found a higher incidence of thyroid disease in patients treated with alemtuzumab and AHSCT, with a higher incidence of infection in AHSCT-treated patients compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.

NEUROLOGY (2021)

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Article Clinical Neurology

Intrathecal immunoglobulins and neurofilament light after autologous haematopoietic stem cell transplantation for multiple sclerosis

Diane Larsson et al.

MULTIPLE SCLEROSIS JOURNAL (2020)

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Article Hematology

Profound but Transient Changes in the Inflammatory Milieu of the Blood During Autologous Hematopoietic Stem Cell Transplantation

Anna Wiberg et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

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Article Biophysics

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)

Basil Sharrack et al.

BONE MARROW TRANSPLANTATION (2020)

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Letter Biophysics

Evaluating the clinical effectiveness of autologous haematopoietic stem cell transplantation versus disease-modifying therapy in multiple sclerosis using a matching-adjusted indirect comparison: an exploratory study from the Autoimmune Diseases Working Party (ADWP) of the European Society of Bone and Marrow Transplantation (EBMT)

P. Tappenden et al.

BONE MARROW TRANSPLANTATION (2020)

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Article Clinical Neurology

Safety and efficacy of autologous hematopoietic stem cell transplantation for multiple sclerosis in Norway

Silje Agnethe Stokke Kvistad et al.

MULTIPLE SCLEROSIS JOURNAL (2020)

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Article Clinical Neurology

Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab

G. Boffa et al.

EUROPEAN JOURNAL OF NEUROLOGY (2020)

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Article Clinical Neurology

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Simon Thebault et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2020)

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Article Surgery

Early changes in IL-21, IL-22, CCL2, and CCL4 serum cytokines after outpatient autologous transplantation for multiple sclerosis: A proof of concept study

Jose C. Jaime-Perez et al.

CLINICAL TRANSPLANTATION (2020)

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Health economics and patient outcomes of hematopoietic stem cell transplantation versus disease-modifying therapies for relapsing remitting multiple sclerosis in the United States of America

Richard K. Burt et al.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2020)

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Article Multidisciplinary Sciences

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

N. Giedraitiene et al.

SCIENTIFIC REPORTS (2020)

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Article Hematology

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

Jeffrey A. Cohen et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2019)

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Article Clinical Neurology

Safety and efficacy of autologous hematopoietic stem-cell transplantation following natalizumab discontinuation in aggressive multiple sclerosis

A. Mariottini et al.

EUROPEAN JOURNAL OF NEUROLOGY (2019)

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Review Pharmacology & Pharmacy

Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders

Yichen Lee et al.

CURRENT PHARMACEUTICAL DESIGN (2019)

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Article Medicine, General & Internal

Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis A Randomized Clinical Trial

Richard K. Burt et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Mireia Sospedra et al.

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Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis

Ilana Katz Sand et al.

MULTIPLE SCLEROSIS JOURNAL (2014)

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Pregnancy after Hematopoietic Cell Transplantation: A Report from the Late Effects Working Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR)

Alison W. Loren et al.

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2011)

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