Four Strategies of Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis Treatment

Conventional therapies do not provide satisfactory control of multiple sclerosis (MS) due to their inability to eradicate self-specific T cell clones. During the last decade high-dose immunosuppressive therapy (HDIT) with autologous haematopoietic stem cell transplantation (AHSCT) has been used with increasing frequency as a therapeutic option for MS patients. We have identified 4 strategies of HDIT+AHSCT depending on the stage in disease process: early, conventional, late, and salvage. In the current study we aimed to study clinical and patient-reported outcomes in MS patients after different strategies of HDIT+AHSCT. One hundred and twenty patients with MS (secondary progressive – 53 patients, primary progressive –21, progressive-relapsing – 9, relapsing-remitting – 37) were included in this study (mean age - 33.0, range: 17–54; male/female – 53/67). Thirty seven patients underwent early transplantation (EDSS 1.0–3.0), 72 patients – conventional transplantation (EDSS 3.5–6.0), 6 patients – late transplantation (EDSS 6.5–7.0), and 5 patients – salvage transplantation (EDSS 7.5–8.5). Median EDSS at baseline was 5.0 (range 1.5 – 8.0). The mean follow-up duration was 18 months (range 6 – 108 months). Neurological and quality of life (QoL) evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter following AHSCT; MRI examinations - at baseline, at 6, 12 months, and at the end of follow-up. Notably, transplantation procedure was well tolerated by the patients with no transplant-related deaths. The efficacy analysis was performed in 79 patients. At 6 months post transplant the following distribution of patients according to clinical response was observed: 42 patients (53%) achieved an objective improvement of neurological symptoms; 37 patients (47%) had disease stabilization. At long-term follow-up clinical response was classified as improvement in 40 patients (50.6%); stabilization in 34 patients (43.1%); progression in 5 patients (1 patient after early transplantation, 3 patients after conventional transplantation, and 1 patient after late transplantation). No active, new or enlarging lesions were registered in patients without disease progression. Furthermore, out of 44 patients included in QoL analysis 39 exhibited improved QoL 6 months post-transplantation. Further QoL improvement was observed at longer follow-up in patients without disease progression. All the patients without disease progression were off therapy throughout the post-transplant period. Thus, AHSCT appears to be an effective treatment for MS both in terms of clinical and patient-reported outcomes. Further studies should be done to establish the best timing for transplantation and to validate high-dose immunosuppressive therapy with ASCT regimens in patients receiving early, conventional, late and salvage transplantation.