Abstract
The immunoablative therapy with hematopoietic stem cell transplantation is tested in patients with intractable form of autoimmune diseases including multiple sclerosis (MS). Thirty one patients with secondary rapidly progressive MS were included in the phase I/II clinical trial involving the high dose chemotherapy with autologous peripheral blood progenitor cell (PBPC) support. Twenty seven patients underwent high dose conditioning BEAM. T cell depletion in vitro was performed in 18 grafts. Nine patients with not purged graft received in vivo ATG 4mg/kg i.v. D+1, D+2 after transplantation. Median follow-up is 48 months (24–72). Median EDSS (Expanded Disability Status Scale) of grafted patients at the time of inclusion was 6.5 (5.0–7.5), median EDSS of grafted patients at the last follow up was 7,0 (5.5–10.0). Two patients out of 27 (7 %) remain improved significantly (by ≥ 1.0 point on EDSS), 3 patients (11 %) are improved not significantly (by 0.5 point). Five patients (19 %) are stable in their EDSS. Seven patients (26 %) gained their disability significantly (by ≥ 1.0 point on EDSS) despite the treatment, one of them died 31 months after the transplantation from disease progression (EDSS 10.0). Ten patients (37 %) worsened not significantly (by 0.5 point) on their EDSS. Patients who clearly stabilized their disability or remain improved represent 37 %. The increase of EDSS at the 48 months (m) of the follow up is significatnt (Wicoxon’s, repeated measure ANOVA, t-test), however, is not at 36, 60 and 72 m respectively. The development of disability between the group that was grafted with in vitro purged graft and the group with ATG i.v. was not significant (Wilcoxon’s, Mann-Whitney). 20 patients stabilized their MRI finding, in 2 patients decreased number and size of lesions, 5 patients worsened their MRI. No mortality has been observed in this cohort. However, the toxicity of the transplantation differed in each individual; two serious events involving respiratory tract have been observed. Changes in lymphocyte subsets in peripheral blood were followed before and after the treatment. The percentage and absolute count of CD4+ cells and CD4+CD45 as well as IRI were significantly decreased 12 months after the transplantation
Conclusion: Almost 40 % of patients with otherwise intractable rapidly progressive MS remained stable or improved in their disability with median follow up 48 months after immunoablative therapy. The value of this type of therapy should be investigated in the randomized trial. The study was sponsored by Grant IGA No NF/6560-3 from Ministry of Health of the Czech Republic.
Author notes
Corresponding author
