High-dose chemotherapy with autologous hematopoietic stem cell transplantation in multiple sclerosis: intermediate results of 3 years research

Relevance. Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system with progressive course. High-dose chemotherapy (HDCT) with autologous haematopoietic stem cell transplantation (AHSCT) is a promising course of treatment-refractory MS. The study aimed to assess the effi cacy and safety of treating MS patients with HDCT + AHSCT.

Material and methods. Were studied 10 people (5 women and 5 men) with relapsing-remitting (30%), secondary progressive (60%) and primary progressive MS (10%). Patients underwent AHSCT using cyclophosphamide + rituximab chemotherapeutic regimen.

Results. In 90% of cases, at least a stabilizing eff ect is shown after the procedure. Only 10% was showed signs of demyelinating activity on MRI of the spinal cord 2 years after HDCT + AHSCT. All patients had a response to therapy according to median Expanded Disability Status Scores (EDSS). We found a positive dynamics of the average EDSS score: before treatment — 5.9 points, 6 months and 1 year after treatment — 5.1 points. There was shown a positive eff ect on dynamics of neurological status, quality of life and emotional state of patients. No treatment-related mortality and uncontrolled complications were revealed.

Conclusion. Timely AHSCT contributes to minimizing the level of disability and signifi cantly improves the quality of life of patients.

1. Shmidt T.E., Yakhno N.N. Multiple sclerosis: A guide for physicians. 7th ed. Moscow: MEDpress-inform, 2021:280 p. (In Russ.).

2. Oh J., Vidal-Jordana A., Montalban X. Multiple sclerosis: clinical aspects. Current opinion in neurology. 2018;31(6):752–759. https://doi.org/10.1097/WCO.0000000000000622

3. Sartori A., Fantini J., Manganotti P. How far away from having an eff ective treatment option for progressive multiple sclerosis are we? Expert opinion on pharmacotherapy. 2017;18(10):953– 955. https://doi.org/10.1080/14656566.2017.1326909

4. Orton S.M., Herrera B.M., Yee I.M., Valdar W., Ramagopalan S.V., Sadovnick A.D., Ebers G.C. Sex ratio of multiple sclerosis in Canada: a longitudinal study. The Lancet. Neurology. 2006;5(11):932–936. https://doi.org/10.1016/S1474-4422(06)70581-6

5. Sharrack B., Saccardi R., Alexander T., Badoglio M., Burman J., Farge D. et al. 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). Bone marrow transplantation. 2020;55(2):283–306. https://doi.org/10.1038/s41409-019-0684-0

6. Cohen J.A., Baldassari L.E., Atkins H.L., Bowen J.D., Bredeson C., Carpenter P.A. et al. Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation. Biology of blood and marrow transplantation. Journal of the American Society for Blood and Marrow Transplantation. 2019;25(5):845–854. https://doi.org/10.1016/j.bbmt.2019.02.014

7. Mancardi G.L., Sormani M.P., Gualandi F., Saiz A., Carreras E., Merelli E. et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015;84(10):981–988. https://doi.org/10.1212/WNL.0000000000001329

8. Burt R.K, Balabanov R., Burman J., Sharrack B., Snowden J.A., Oliveira M.C. et al. Eff ect 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. JAMA. 2019;321(2):165–174. https://doi.org/10.1001/jama.2018.18743

9. Nash R.A., Hutton G.J., Racke M.K., Popat U., Devine S.M., Griffi th L.M. et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report. JAMA. 2015;72(2):159–169. https://doi.org/10.1001/jamaneurol.2014.3780

10. Nash R.A., Hutton G.J., Racke M.K., Popat U., Devine S.M., Steinmiller K.C. et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88(9):842–852. https://doi.org/10.1212/WNL.0000000000003660

11. Moore J.J., Massey J.C., Ford C.D., Khoo M.L., Zaunders J.J., Hendrawan K. et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. Journal of neurology, neurosurgery, and psychiatry. 2018;90(5):12. 514–521. https://doi.org/10.1136/jnnp2018-319446

12. Muraro P.A., Pasquini M., Atkins H.L., Bowen J.D., Farge D., Fassas A. et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA. 2017;74(4):459–469. https://doi.org/10.1001/jamaneurol.2016.5867

13. Burt R.K., Han X., Quigley K., Helenowski I.B., Balabanov R. Real-world application of autologous hematopoietic stem cell transplantation in 507 patients with multiple sclerosis. Journal of neurology. 2022;269(5):2513–2526. https://doi.org/10.1007/s00415-021-10820-2

14. Boff a G., Massacesi L., Inglese M., Mariottini A., Capobianco M. Lucia M. et al. Long-Term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis. Neurology. 2021;97(4):203. https://doi.org/10.1212/WNL.0000000000011461

15. Muraro P.A., Martin R., Mancardi G.L., Nicholas R., Sormani M.P., Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nature reviews. Neurology. 2017;13(7):391–405. https://doi.org/10.1038/nrneurol.2017.81

16. Genc B., Bozan H.R., Genc S., Genc K. Stem Cell Therapy for Multiple Sclerosis. Advances in experimental medicine and biology. 2019;1084:145–174. https://doi.org/10.1007/5584_2018_247