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Research paper
Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis
  1. John J Moore1,
  2. Jennifer C Massey2,
  3. Carole D Ford3,
  4. Melissa L Khoo3,
  5. John J Zaunders4,
  6. Kevin Hendrawan3,
  7. Yael Barnett5,
  8. Michael H Barnett6,
  9. Kain A Kyle6,
  10. Robert Zivadinov7,
  11. Kris C Ma,
  12. Sam T Milliken1,
  13. Ian J Sutton2,
  14. David D F Ma1
  1. 1 Department of Haematology, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
  2. 2 Department of Neurology, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
  3. 3 Blood Stem cells and Cancer Laboratory, St. Vincent’s Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia
  4. 4 Immunology Laboratory, St. Vincent’s Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia
  5. 5 Radiology Department, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
  6. 6 Sydney Neuroimaging Analysis Centre, Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia
  7. 7 Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA
  1. Correspondence to John J Moore, Department of Haematology, St. Vincent’s Hospital, Darlinghurst, NSW 2010, Australia; jmoore{at}


Background Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.

Methods This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.

Outcomes The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.

Results Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12–66). The median Expanded Disability Status Scores (EDSS) was 6 (2–7) and patients had failed a median of 4 (2–7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+ T regulatory cells, immunosuppressive CD56hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.

Conclusions The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.

Trial registration number ACTRN12613000339752.

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  • Contributors JJM, STM, IJS and DDFM designed the clinical trial. JJM, JJZ, RZ, MHB, IJS and DDFM designed the research methodology. JJM, JCM, CDF, MLK, YB and KAK performed research. JCM, CDF, MLK, KH, YB, KAK, KCM and DDFM analysed data. JJM, JCM, CDF, MLK, KAK, IJS and DDFM wrote the manuscript. All authors reviewed and edited the final manuscript.

  • Funding Support for the following research has been provided by research scholarships and grants by MSRA, NHMRC, St. Vincent’s Clinic Research Foundation, Maple-Brown Family Charitable Foundation, Reset Australia, John Kirkpatrick Medical Foundation.

  • Competing interests IJS reports personal fees from Biogen, Merck, Sanofi Genzyme and Teva, outside the submitted work. JCM reports personal fees from Biogen, Merck, Sanofi Genzyme and Teva, outside the submitted work. YB reports grants and other from Genzyme-Sanofi, grants and other from Novartis, grants from Biogen, other from Teva, grants and other from Merck outside the submitted work and YB is a cofounder of Medical Safety Systems, which provides automated pathology monitoring for patients prescribed immunotherapies (including alemtuzumab) in Australia and (under the trading name RxMx) the USA. RZ has received speaker honoraria and consultant fees from Genzyme-Sanofi, Novartis, Claret Medical, Celgene and EMD Serono. He has received research support from EMD Serono, Genzyme-Sanofi, Claret Medical, Protembis, QuintilesIMS and Novartis. outside the submitted work. DDFM has received a research grant from Phebra outside the submitted work.

  • Patient consent Not required.

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