Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This... Show moreThree randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multicenter, prospective, non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult patients with systemic sclerosis undergoing a first autologous hematopoietic stem cell transplant between December 2012 and February 2016 were prospectively included in the study. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty patients with systemic sclerosis were included. The median duration of the follow-up was 24 (range, 6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulin conditioning for all, with CD34(+) selection in 35 patients. At 2 years, the progression-free survival rate was 81.8%, the overall survival rate was 90%, the response rate was 88.7% and the incidence of progression was 11.9%. The 100-day non-relapse mortality rate was 6.25% (n=5) with four deaths from cardiac events, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (P<0.001). By multivariate analysis, baseline skin score >24 and older age at transplantation were associated with lower progression-free survival (hazard ratios 3.32 and 1.77, respectively). CD34(+)-cell selection was associated with better response (hazard ratio 0.46). This study confirms the efficacy of autologous stem cell transplantation, using non-myeloablative conditioning, in real-life practice for severe systemic sclerosis. Careful cardio-pulmonary assessment to identify organ involvement at the time of the patient's referral, reduced cyclophosphamide doses and CD34(+)-cell selection may improve outcomes. Show less
These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune... Show moreThese updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials. Show less
