Changes to the immune system following AHSCT for MS - MS Research Australia

Changes to the immune system following AHSCT for MS

Jennifer Massey

The University of NSW and St Vincent’s Hospital, NSW

| Better treatments | Immunology | Scholarship | 2017 | Investigator Led Research |
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Summary

Autologous haematopoietic stem cell transplant (AHSCT, also known as bone marrow transplant) is an immunosuppressive chemotherapy treatment combined with reinfusion of blood stem cells to help re-build the immune system. It has been used to treat a small percentage of people with MS in Australia and internationally.

The aim of AHSCT is to ‘re-boot’ the immune system so that the self-reactive immune cells that are attacking an individual’s brain and spinal cord are removed, and replaced with the regenerated immune system. The regenerated immune system is thought to be more ‘self-tolerant’ and less likely to continue attacking the body. It is currently unclear, at a cellular level, how AHSCT produces these effects on the immune system, but it is thought to be linked to a type of immune cell called a T cell.

Dr Jennifer Massey, a clinician currently receiving advanced training in neurology, will undertake a postgraduate scholarship to examine changes to T cells in the blood of people with MS following treatment with AHSCT. She will determine whether the treatment and the clinical and immune system characteristics of the people treated with AHSCT alters the way that the T cells are affected by the treatment and whether they can be used to predict which patients will have the most long-term benefit from the treatment as determined by clinical and magnetic resonance imaging (MRI) outcomes.

This research will add to the international body of work that is aiming to produce treatment guidelines for the use of AHSCT in the treatment of MS. It will also help us to understand how the treatment works at the level of the immune system and potentially lead to other strategies to reset the immune system that do not require such intensive chemotherapy treatments.

Progress to Date

The first stage of Dr Massey’s research has collated detailed information and tracking of people who are undergoing AHSCT at St Vincent’s Hospital in Sydney to be included in this study as well as national and international registries. Dr Massey has also streamlined the clinical approach for these patients as well as incorporated perspectives from neurology and haematology departments from the hospital in order to ensure the best outcomes for patients. Dr Massey has also established collaborations with the neuroradiology department at the Sydney Neuroimaging Analysis Centre at the University of Sydney and conducted a retrospective analysis of all imaging undertaken on AHSCT patients.

To date Dr Massey has collated the clinical data of MS patients undergoing AHSCT at St Vincent's Hospital and analysed the outcomes. The results of this study have been published in the Journal of Neurology, Neurosurgery and Psychiatry. A separate commentary on the results of this study can be found here.

Immune blood cells have been collected from people with MS who have undergone AHSCT. Dr Massey has analysed the composition of the immune cells before and after AHSCT and is monitoring how different populations of immune cells respond and recover following AHSCT.  She is also looking specifically at a subset of immune cells known as T cells, and is using advanced DNA sequencing technologies to develop an in-depth view of changes in T cells during AHSCT and other MS therapies which deplete the immune system. The DNA sequencing is complete and the data analysis is underway.

Dr Massey has presented her findings at a number of national and international conferences. Dr Massey continues as an active neurology trainee and has published a range of journal papers related to her clinical work over above those related to this project (listed below).

Publications

  • Massey JC, Sutton IJ, Ma DDF, Moore JJ. Regenerating Immunotolerance in Multiple Sclerosis with Autologous Hematopoietic Stem Cell Transplant. Front Immunol. 2018 9:410.
  • Moore J, Massey J, Ford C. et al. ‘A prospective phase II clinical trial of Autologous Haematopoietic Stem Cell Transplantation for active, treatment refractory multiple sclerosis.’  JNNP, Oct 2018.

For information on AHSCT for MS and MS Research Australia’s position statement please see here.

Updated: 31 March 2019

Updated: 02 February, 2017

Investigator

  • Jennifer Massey, The University of NSW and St Vincent’s Hospital, NSW

Supervisor

Grant Awarded

  • Postgraduate Scholarship

Total Funding

  • $100,000

Duration

  • 3 years over 2017- 2019

Funding Partner

  • MS Angels
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