Autologous hematopoietic stem-cell transplantation in neurological disorders: current approach and future directions

ABSTRACT

Introduction

Autologous hematopoietic stem-cell transplantation (AHSCT) has become increasingly popular in recent years as an effective treatment of immune-mediated neurological diseases. Treatment-related mortality has significantly reduced primarily through better patient selection, optimization of transplant technique, and increased center experience.

Area covered

Multiple sclerosis is the main indication, but people with neuromyelitis optica spectrum disorder, stiff-person spectrum disorder, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, and other immune-mediated neurological disorders also have been treated. The review herein discusses the use of AHSCT in these neurological disorders, the importance of patient selection and transplant technique optimization and future directions.

Expert opinion

Phase II and III clinical trials have confirmed the safety and efficacy of AHSCT in multiple sclerosis and recent phase II clinical trials have also suggested its safety and efficacy in chronic inflammatory demyelinating polyneuropathy and neuromyelitis optica spectrum disorder, with the evidence in other neurological disorders limited to individual case reports, small case series, and registry data. Therefore, further randomized controlled clinical trials are required to assess its safety and efficacy in other neurological conditions. However, in rare neurological conditions, pragmatic treatment trials or registry-based studies may be more realistic options for gathering efficacy and safety data.

KEYWORDS:

• Autologous hematopoietic stem-cell transplantation
• multiple sclerosis
• neuromyelitis optica spectrum disorder
• stiff-person spectrum disorder
• chronic inflammatory demyelinating polyneuropathy
• POEMS syndrome
• myasthenia gravis

Article highlights

• The efficacy and safety of AHSCT in immune-mediated neurological diseases have been increasing through improved patient selection, optimization of transplant technique and increased center experience for the last two decades.

• MS is the main indication for using AHSCT in immune-mediated neurological disorders, but the spectrum of these disorders is gradually increasing.

• A recently published phase III RCT showed that AHSCT is more efficacious than standard DMTs for MS.

• A phase III RCT, STAR-MS, which is going to compare AHSCT with high efficacy DMTs in people with MS will start recruitment in near future.

• The choice of conditioning regimen for AHSCT is a trade-off between safety and efficacy. A retrospective comparative study between BEAM + ATG and Cy + ATG is underway, which are two EBMT recommended conditioning regimens used to treat patients with MS and other immune-mediated neurological diseases.

• Further studies of immune reconstitution are warranted to define the mechanism of action which in turn may help to fine tune the transplant technique, improve our understanding of pathogenesis and identify biomarkers for disease activity and treatment response.

• Underlying pathophysiology is needed to be taken into consideration when choosing a conditioning regimen to ablate the immune system.

• AHSCT for autoimmune conditions should be performed at Joint Accreditation Committee ISCT-Europe & EBMT (JACIE) approved (or equivalent) centers by a multi-disciplinary team consisting of transplant specialists, neurologists, other supporting clinicians (such as fertility services) and various allied health-care professionals, as the TRM reduces with increase in center experience.

Acknowledgments

The authors acknowledge the support of NIHR Sheffield Biomedical Research Centre and Sheffield Hospitals Charity. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and social Care.

Declaration of interest

J Snowden declares speaker fees at educational events supported by Sanofi, Janssen, Jazz, Mallinckrodt and Gilead. J Snowden is a member of a trial IDMC for Kiadis Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.