High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in multiple sclerosis: approaches to risk management

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Abstract

Introduction. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT/AHSCT) is a promising and effective method for treating immune disorders, including multiple sclerosis (MS). The frequency and severity of adverse effects from therapy have decreased significantly over the last 20 years due to a reduction in conditioning regimen intensity, changes in patient selection, and the accumulated experience of the transplantation centres.

Study aim: to analyse the published data on HDIT/AHSCT complications in MS and ways to reduce their risk.

Materials and methods. We analysed and summarized the research findings regarding conditioning regimen protocols for HDIT/AHSCT, early and late complications, and risk factors associated with treatment recipients.

Results. HDIT/AHSCT may have a wide range of serious complications. However, the shift to less intense conditioning regimens and stricter patient selection criteria have minimized adverse events. The latest moderate-intensity protocols may be less effective than high-intensity protocols, but their timely use may provide the maximum benefit to people with MS refractory to standard treatment. HDIT/AHSCT cannot be the method of choice for all categories of patients with MS, because expectations may not be met due to the significant risk of complications, in particular, in cases of long-term disease, significant neurological deficit, and no disease activity. The maximum effect should be expected in early or emergency HDIT/AHSCT.

Conclusion. This information can be used to justify further expansion of the medical assistance provided to patients with MS in the Russian Federation.

About the authors

Alexey Yu. Polushin

Pavlov University

Author for correspondence.
Email: alexpolushin@yandex.ru
ORCID iD: 0000-0001-8699-2482

Cand. Sci. (Med.), Chief, Chemotherapy and SCT department for cancer and AID, Head, Laboratory of neurooncology and AID, R.M. Gorbacheva Research Institute, Associate Professor, Department of Neurology

Russian Federation, Saint Petersburg

Yuri R. Zalyalov

Pavlov University

Email: yz21@mail.ru
ORCID iD: 0000-0002-3881-4486

Cand. Sci. (Med.), Head, Chemotherapy and SCT unit for cancer and AID

Russian Federation, Saint Petersburg

Natalia A. Totolyan

Pavlov University

Email: ntotolyan@mail.ru
ORCID iD: 0000-0002-6715-8203

D. Sci. (Med.), Professor, Department of neurology

Russian Federation, Saint Petersburg

Alexander D. Kulagin

Pavlov University

Email: kulagingem@rambler.ru
ORCID iD: 0000-0002-9589-4136

D. Sci. (Med.), Director, R.M. Gorbacheva Research Institute, Head, Professor, B.V. Afanasyev Department of hematology, transfusion medicine and transplantation with the course of pediatric oncology

Russian Federation, Saint Petersburg

Alexander A. Skoromets

Pavlov University

Email: askoromets@gmail.com
ORCID iD: 0000-0002-5884-3110

D. Sci. (Med.), Professor, Academician of RAS, Department of neurology

Russian Federation, Saint Petersburg

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2. HSCT activity in the treatment of MS at European centres, according to the EBMT registry data (adapted from [3, 11]). А — increased number of cyclophosphamide conditioning regimens (Cy-ATG), alongside a mild decrease in moderate-intensity regimens (ВЕАМ), 2017 data are partially provided; В — increased transplant use and decreased mortality despite a higher number of cyclophosphamide conditioning regimens. Mortality is shown as %. The number of HDIT-AHSCT and the number of TRM are shown fractious.

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Copyright (c) 2022 Polushin A.Y., Zalyalov Y.R., Totolyan N.A., Kulagin A.D., Skoromets A.A.

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