Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series

Giovanna S Manzano; Kathryn B Holroyd; Tamara Kaplan; Shamik Bhattacharyya; Tanuja Chitnis; Gladia Hotan; Jonathan Zurawski; Kristin M Galetta; Farrah J Mateen

doi:10.1016/j.msard.2022.103861

Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series

Mult Scler Relat Disord. 2022 Jul:63:103861. doi: 10.1016/j.msard.2022.103861. Epub 2022 May 10.

Authors

Giovanna S Manzano¹, Kathryn B Holroyd², Tamara Kaplan², Shamik Bhattacharyya², Tanuja Chitnis², Gladia Hotan³, Jonathan Zurawski², Kristin M Galetta², Farrah J Mateen⁴

Affiliations

¹ Department of Neurology, Division of Neuroimmunology and Neuroinfectious Diseases, Massachusetts General Hospital, 15 Parkman Street, Wang 8-835, Boston, MA 02114, United States; Harvard Medical School, Boston, MA, United States. Electronic address: gmanzano@partners.org.
² Harvard Medical School, Boston, MA, United States; Department of Neurology, Brigham Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, United States.
³ Institute of High Performance Computing, A*STAR, Singapore.
⁴ Department of Neurology, Division of Neuroimmunology and Neuroinfectious Diseases, Massachusetts General Hospital, 15 Parkman Street, Wang 8-835, Boston, MA 02114, United States; Harvard Medical School, Boston, MA, United States.

PMID: 35576727
DOI: 10.1016/j.msard.2022.103861

Abstract

Background: Stem cell therapies (SCT) have not received formal regulatory approval for the treatment of people with multiple sclerosis (PwMS), but PwMS may seek various options on their own accord. The current literature largely focuses on the efficacy and safety of SCT in PwMS in clinical trials, in particular autologous hematopoietic stem cell transplantation (aHSCT), in carefully selected participants. There is little reported on the MS disease modifying therapy (DMT) management of PwMS who choose to undergo SCT outside of these trials.

Methods: We identified PwMS from two academic centers who had MS diagnosis fulfilling 2017 McDonald criteria and received SCT (methodologies permitted: aHSCT, umbilical-derived mesenchymal stem cells and/or adipose-derived mesenchymal stem cells (AdMSC)), with the goal to treat MS, between 1/1/2015 and 11/30/2021.

Results: Nine PwMS (five females; age range at SCT treatment 25-69 years old; MS disease duration 1-12 years; six relapsing-remitting, three secondary progressive, one primary progressive) underwent a total of eleven SCTs (nine aHSCT, two AdMSC, one umbilical-derived MSC) with the goal to treat MS. Two of six PwMS who underwent SCT <10 years from MS diagnosis, and one of three PwMS who underwent stem cell therapies >10 years from MS diagnosis were clinically stable thereafter. An MS DMT was resumed in five PwMS afterwards, including rituximab, ocrelizumab, siponimod, and glatiramer acetate: one remained clinically stable, whereas four clinically progressed. Four PwMS remained off of a DMT: three were clinically stable, whereas one clinically progressed. All nine patients demonstrated radiographic stability by MRI after SCT. Only one met formal criteria to consider aHSCT for MS.

Conclusions: We demonstrate the heterogeneous real-world experience of treating MS after patient-chosen experimental SCTs, detailing the range of DMT management in various patient circumstances. Limitations of our study include its small sample size and the variety of stem cell therapies received.

Keywords: Case series; Disease modifying therapies; Immunosuppression; Multiple sclerosis; Stem cell therapies.

MeSH terms

Adult
Aged
Female
Humans
Middle Aged
Multiple Sclerosis* / therapy
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Retrospective Studies
Stem Cells
Treatment Outcome