Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Predicting the response to hematopoietic stem cell transplantation in persons with multiple sclerosis: the significance of an early positive response

Bone Marrow Transplantation (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, gliosis, and inflammation; it is a multifactorial disease influenced by genetic susceptibility and environmental factors such as viral infections, vitamin D levels and geography. Typically emerging between ages 20 and 30, MS is more prevalent in women [1,2,3]. Symptoms vary depending on lesion location and may include muscle weakness, sensory deficits, optic neuritis, and brainstem syndromes. Diagnosis relies on clinical evaluation supported by MRI findings and, when necessary, cerebrospinal fluid oligoclonal bands, as defined by the 2017 McDonald criteria [2]. Autologous hematopoietic stem cell transplantation (aHSCT) is an effective therapy for MS; it combines immune ablation with reinfusion of the patient’s own stem cells to reset immune function [4]. Evidence supports its ability to control disease activity and reduce disability progression, especially in relapsing-remitting MS (RRMS) [5,6,7]. Our prior data showed positive responses across all MS subtypes using our immunoablative protocol [7]. This prospective study aims to identify variables associated with early therapeutic response at three months post-aHSCT and to assess its prognostic implications. All consecutive MS patients referred to Clínica Ruiz for aHSCT between May 2015 and June 2024 were included Participants had RRMS, secondary progressive (SPMS), or primary progressive (PPMS) forms of the disease, with a Karnofsky score >70% and EDSS ≤ 8 within two weeks prior to transplantation. None had prior exposure to myelotoxic agents, and all had normal blood counts at mobilization. A minimum three-month washout from prior immunosuppressive treatments was required. Pre-transplant EDSS evaluations were consistently performed by the same neurologist. The protocol was approved by the Ethics Committee of Clínica Ruiz, and all participants provided informed consent; the study is registered at ClinicalTrials.gov (NCT02674217). Peripheral blood stem cell mobilization and apheresis were conducted as previously described [7]. The goal of the apheresis was to collect a minimum of 1 ×106 viable CD34+ cells per kilogram of body weight. The aHSCT was performed using the “Mexican method” [7]: Cyclophosphamide was administered at a total dose of 200 mg/kg: the first two doses (50 mg/kg each) were given over two consecutive days, while the remaining two doses were administered one week later, also on successive days. Once the granulocyte count recovered, a fixed dose of rituximab, 1000 mg. was delivered. The apheresis products obtained on day -1 were stored in a conventional blood bank refrigerator (Thermoforma, Marietta, OH, USA), and reinfused to the patients on day 0.

A positive response was defined as stable or improved EDSS post-aHSCT; any EDSS increase was considered no response. Disability progression was defined as a ≥1.0 EDSS increase in patients with EDSS ≤ 5.5 or ≥0.5 in those with EDSS > 5.5, confirmed if sustained for 3 months over 2 years. For early response analysis, baseline EDSS was compared to 3-month scores using Student’s T test (GraphPad Prism). A subgroup with 12- and 24-month follow-up was derived and classified by response status. ANOVA was used to assess outcomes across time points.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Response rate at 3, 12 and 24 months after autologous hematopoietic stem cell transplantation in 201 patients with relapsing remitting (RRMS), primary progressive (PPMS) and secondary progressive (SPMS) forms of multiple sclerosis.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to patient confidentiality regulations but are available from the corresponding author on reasonable request and with appropriate institutional approval.

References

  1. Zurawski J, Stankiewicz J. Multiple sclerosis re-examined: essential and emerging clinical concepts. Am J Med. 2018;131:464–72. https://doi.org/10.1016/j.amjmed.2017.11.044

    Article  PubMed  Google Scholar 

  2. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA. 2021;325:765–79. https://doi.org/10.1001/jama.2020.26858

    Article  CAS  PubMed  Google Scholar 

  3. Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, et al. Multiple sclerosis. Nat Rev Dis Prim. 2018;4:43. https://doi.org/10.1038/s41572-018-0041-4

    Article  PubMed  Google Scholar 

  4. Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, Carpenter PA, et al. Autologous hematopoietic cell transplantation for treatment-refractory relapsing multiple sclerosis: position statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019;25:845–54. https://doi.org/10.1016/j.bbmt.2019.02.014

    Article  PubMed  Google Scholar 

  5. Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology. 2017;88:2115–22. https://doi.org/10.1212/WNL.0000000000003987

    Article  PubMed  Google Scholar 

  6. Boffa G, Massacesi L, Inglese M, Mariottini A, Capobianco M, Moiola L, et al. Long-term clinical outcomes of hematopoietic stem cell transplantation in multiple sclerosis. Neurology. 2021;96:e1215–e1226. https://doi.org/10.1212/WNL.0000000000011461

    Article  CAS  PubMed  Google Scholar 

  7. Ruiz-Argüelles GJ, Olivares-Gazca JC, Olivares-Gazca M, Leon-Peña AA, Murrieta-Alvarez I, Cantero-Fortiz Y, et al. Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center. Clin Exp Immunol. 2019;198:351–8. https://doi.org/10.1111/cei.13358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lira-Lara O, Robles-Nasta M, Olivares-Gazca JC, Kharfan-Dabaja M, Rivera-Álvarez M, García-Vélez D, et al. Early morbimortality in autologous hematopoietic cell transplantation performed on outpatient basis in patients with autoimmune diseases: experience in 1700 patients. Bone Marrow Transpl. 2025;60:640–4. https://doi.org/10.1038/s41409-025-02544-y

    Article  CAS  Google Scholar 

  9. Snowden JA, Sharrack B, Akil M, Kiely DG, Lobo A, Kazmi M, et al. Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases—a guide for the generalist. Clin Med. 2018;18:329–34. https://doi.org/10.7861/clinmedicine.18-4-329

    Article  Google Scholar 

  10. Msheik A, Assi F, Hamed F, Jibbawi A, Nakhl AM, Khoury A, et al. Stem cell transplantation for multiple sclerosis: a 2023 review of published studies. Cureus. 2023;15:e47972. https://doi.org/10.7759/cureus.47972

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kazmi M, Muraro PA, Mehra V, Gabriel I, De Matteis E, Brittain G, et al. Autologous haematopoietic stem cell transplantation for multiple sclerosis in the UK: a 20-year retrospective analysis of activity and haematological outcomes from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT). Br J Haematol. 2025;207:977–91. https://doi.org/10.1111/bjh.20199

Download references

Author information

Authors and Affiliations

  1. Centro de Hematología y Medicina Interna, Puebla, México

    Miguel A. Viveros-Lugo, Gloria E. Cruz-Pérez, Danae García-Vélez, Sofia Chávez-Martinez, Michelle Lavoignet-Cisneros, Mónica D. Salgado-Cabrera, Olivia Lira-Lara, Max Robles-Nasta, Juan Carlos Olivares-Gazca, Guillermo J. Ruiz-Delgado & Guillermo J. Ruiz-Arguelles

  2. Facultad de Medicina, Universidad Anáhuac Puebla, Puebla, México

    Miguel A. Viveros-Lugo

  3. Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, Puebla, México

    Gloria E. Cruz-Pérez, Danae García-Vélez, Sofia Chávez-Martinez, Max Robles-Nasta, Juan Carlos Olivares-Gazca, Guillermo J. Ruiz-Delgado & Guillermo J. Ruiz-Arguelles

  4. Facultad de Medicina, Universidad Veracruzana, Veracruz, México

    Michelle Lavoignet-Cisneros & Olivia Lira-Lara

  5. Facultad de Medicina, Universidad de Las Américas Puebla, Puebla, México

    Mónica D. Salgado-Cabrera & Juan Carlos Olivares-Gazca

Authors
  1. Miguel A. Viveros-Lugo
    View author publications

    Search author on:PubMed Google Scholar

  2. Gloria E. Cruz-Pérez
    View author publications

    Search author on:PubMed Google Scholar

  3. Danae García-Vélez
    View author publications

    Search author on:PubMed Google Scholar

  4. Sofia Chávez-Martinez
    View author publications

    Search author on:PubMed Google Scholar

  5. Michelle Lavoignet-Cisneros
    View author publications

    Search author on:PubMed Google Scholar

  6. Mónica D. Salgado-Cabrera
    View author publications

    Search author on:PubMed Google Scholar

  7. Olivia Lira-Lara
    View author publications

    Search author on:PubMed Google Scholar

  8. Max Robles-Nasta
    View author publications

    Search author on:PubMed Google Scholar

  9. Juan Carlos Olivares-Gazca
    View author publications

    Search author on:PubMed Google Scholar

  10. Guillermo J. Ruiz-Delgado
    View author publications

    Search author on:PubMed Google Scholar

  11. Guillermo J. Ruiz-Arguelles
    View author publications

    Search author on:PubMed Google Scholar

Contributions

MAVL led the development of the study protocol and final report, performed the literature search, handled data extraction and analysis, interpreted the findings, generated tables and figures, and updated the reference list. GECP contributed to drafting the report, data extraction and analysis, and interpretation of the results. DGV was involved in the protocol design, data analysis, and interpretation of outcomes. SCM contributed to manuscript drafting, proofreading, and making grammatical corrections. MRN, OLL, MLC, and MDSC assisted with data extraction and sourcing bibliographic references. JCOG and GJRD participated in the protocol design and manuscript revision. GJRA was responsible for conceptualizing the study, providing key analytical tools, conducting data analysis, and contributing to manuscript writing.

Corresponding author

Correspondence to Guillermo J. Ruiz-Arguelles.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All methods were performed in accordance with Helsinki Declaration and national regulations. The protocol was approved by the Institutional Review Board of the Clínica Ruiz (CEI-10-03-24-02). Informed consent was obtained from all participants. The protocol has been registered in ClinicalTrials.govNCT02674217.

Consent for publication

Consent for publication Informed consent Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Viveros-Lugo, M.A., Cruz-Pérez, G.E., García-Vélez, D. et al. Predicting the response to hematopoietic stem cell transplantation in persons with multiple sclerosis: the significance of an early positive response. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02707-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-025-02707-x

Search

Advanced search

Quick links