In search of lost disease : Clinical, qualitative and imaging studies to investigate long-term effects of autologous haematopoietic stem cell transplantation for multiple sclerosis

Abstract

With the introduction of autologous haematopoietic stem cell transplantation (AHSCT) for the treatment of multiple sclerosis (MS), there are now individuals living without experiencing disease activity of MS. Are they cured?  There is a need for terminology to describe the state of these individuals. To address this and to report the ten-year outcomes of the first ten persons treated with AHSCT for MS at our centre, we conducted tests involving six different outcome measures to encompass the inflammatory (new clinical relapses, new MRI lesions, intrathecal antibody production) and degenerative (clinical progression, elevated intrathecal levels of neurofilament light protein, presence of callosal atrophy) aspects of the disease. Half of the participants achieved ‘sustained complete remission’ (normal values in all parameters, excluding intrathecal measurements), and three ‘resolved disease’ by displaying standard values across all measures. This terminology can be used when communicating successful treatment outcomes, and ‘resolved disease’ might serve as a working definition of cure. How did one perceive oneself, one’s health, and one’s diagnosis ten years after AHSCT? In this qualitative interview study, the lived experience of the same persons was explored and analysed with qualitative content analysis. The treatment symbolised a transition from a life dominated by uncertainty to a state of health and normality. The participants shared their experience of now feeling healthy, and some even reported not having MS anymore. They expressed a desire for objective criteria to affirm their health status. Impaired cerebral blood flow has been linked to progressive MS. The third study was a case-control study examining CBF and cerebrovascular reactivity (CVR) in individuals with secondary progressive MS, healthy controls, and persons treated with AHSCT from the previous studies. CBF was measured using positron emission tomography with 15O-water. CBF was diminished in individuals with progressive MS compared to the healthy controls. In contrast, CBF in the AHSCT group did not differ significantly from healthy controls. CVR was not impaired in progressive MS patients, suggesting an opportunity for therapeutic intervention with a vasodilating agent. The fourth study was a case-control study assessing factors associated with a favourable response to COVID-19 vaccination in persons with rituximab and MS. B cells emerged as the sole factor influencing antibody production. Consequently, pre-vaccination B-cell measurement was advised to enhance the likelihood of an effective humoral immune response