Assistant Professor of Neurology, Weill Cornell Medical College; Assistant Attending Neurologist, New York-Presbyterian Hospital
SYNOPSIS: This retrospective study of autologous hematopoietic stem cell transplantation in patients with active relapsing remitting multiple sclerosis or progressive multiple sclerosis showed efficacy in relapse rate reduction and on magnetic resonance imaging and disability outcomes during a median post-transplant follow-up of about two years. There were risks, including death, associated with the treatment.
SOURCE: Nicholas RS, Rhone EE, Mariottini A, et al; London Group on Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. Autologous hematopoietic stem cell transplantation in active multiple sclerosis: A real-world case series. Neurology 2021;97:e890-e901.
Clinical trials of autologous hematopoietic stem cell transplantation in patients with multiple sclerosis have demonstrated efficacy in controlling the disease. Stem cell therapy also is being used increasingly in clinical practice for patients refractory to current immunosuppressive medications. In this study, the authors examined the application of autologous hematopoietic stem cell transplantation (AHSCT) in relapsing remitting multiple sclerosis (RRMS) and progressive MS patients with active disease in a real-world scenario.
The authors reviewed data on consecutive MS patients who underwent AHSCT at two tertiary care hospitals in London, United Kingdom. Data were collected retrospectively. The study included patients who had at least six months of post-transplant follow-up or who died at any time after the transplant. AHSCT was conducted under the standard protocol for the procedure at the respective hospitals, but the procedures were not identical. A total of 120 patients were included in the analysis. Sixty-two (52%) had either primary or secondary progressive MS, and the others had RRMS. Among patients for whom data were available, 90% had evidence of new magnetic resonance imaging (MRI) activity prior to the therapy. The mean age of the patients was 42.3 years, the median Expanded Disability Status Scale (EDSS) score was 6.0, and the mean disease duration was 8.8 years.
The annualized relapse rate decreased from 0.46 ± 0.57 in the two years prior to the procedure to 0.08 ± 0.38 in the four years post-transplant (P < 0.001). Ninety-three percent of the patients were relapse-free at two years. There was a significant reduction in the number of new T2 lesions, with 90% of the patients being free of new lesions at two years post-transplant. On analysis of disability, the average EDSS score for the group increased by 0.25 in the 12 months preceding AHSCT and 0.02 in the 12 months post-transplant. In a subgroup analysis, the RRMS cohort showed a mild improvement in EDSS score, while the progressive MS cohort continued to have a worsening of EDSS score. In the RRMS group, the EDSS score had increased by 0.39 prior to AHSCT and decreased by 0.17 after; in the progressive group there was an increase of 0.11 before AHSCT and 0.24 after.
Regarding adverse events, there were three deaths within 100 days of the procedure. Two were the result of cardiac arrest (in the setting of pulmonary edema in one case and electrolyte abnormalities in the other). The third fatality was caused by acute respiratory distress syndrome secondary to pneumonia and sepsis. Other significant adverse events included cytomegalovirus reactivation, which was controlled on antiviral therapy; and seven patients developed secondary autoimmune disorders (six cases of thyroiditis and one case of thrombocytopenia).
The authors concluded that the efficacy in this real-world data analysis matches that demonstrated in clinical trials of AHSCT in MS but stated that risks appeared higher in this study compared to clinical trials. These risks were in the immediate aftermath of the treatment. The investigators pointed out that one should weigh this against any potential long-term complications from continued immunosuppression associated with current aggressive treatments for MS. Limitations of this study also include the relatively short duration of post-transplant follow-up and the retrospective nature of the analysis.
The efficacy of AHSCT in active MS patients in this real-world data analysis appears comparable to that demonstrated in clinical trials and selected published case series. This study shows impressive efficacy, which will need to be weighed against potential risks. The most concerning adverse effect is the mortality and morbidity in the immediate post-procedure period. Special attention and focus on mitigation strategies and more experience could result in safer protocols that lower this risk.
Another aspect of AHSCT that needs more data is the durability of effect. One would need studies with longer follow-up of patients who have undergone this procedure to assess long-term benefits and risks. With more data and better safety, AHSCT has the potential to grow into a valuable treatment option for a wider spectrum of patients with MS.