Long Term Outcomes of Autologous Hematopoietic Stem Cell Transplantation in Progressive Multiple Sclerosis
Authors: Xu Juan , Wu Tong , Su Li , Ji Bing Xin , Hui Wu Han 
Published: April 2020

Abstract
Background Progressive multiple sclerosis (MS) is going with continuously disability and unresponsive to high dose steroid and immunomodulation. The autologous hematopoietic stem cell transplantation (ASCT) has been introduced in treatment of the forms of multiple sclerosis. Due to hematopoitic stem cell transplantation involved two processes that are conditioning with high dose immunosuppressive agents and stem cell transfusion. The short term outcomes (within 2 years after transplantation) do not preclude the immunosuppressant roles of conditionings, therefore the long term clinical outcomes after ASCT were evaluated for patients with progressive MS. Methods From Nov. 2001 to Jun. 2008, 34 patients with secondary progressive MS were treated with ASCT in our hospital. Of which, 26 patients were followed up more than 2 years till now. The median follow-up time was 40 months (3–83). There were 25 females (73.5%) and 9 males (26.5%). The median age of the patients was 36(20–51) years. Medium duration of disease was 36 months (15–156), and medium attacking interval time was 6.5 months (4–12). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. BEAM, Tiniposide(600 mg/m2), melphalan(140mg/ m2), carmustin (300 mg/m2)and cytosine arabinoside (800 mg/m2), were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale (EDSS). No maintenance treatment was administered if no disease progression. Results No deaths occurred following the treatment. All patients were observed into two groups, active-free group and activity group. The former include neurological improvement and neurological stabilization after transplantation. The latter include activity with progression and relapse without progression after improvement. Among 34 patients, 27 patients were in active-free group. Of twenty-one patients were with continuous neurological improvement without any active events. Median EDSS scores decreased from 6.0 (4.5–7.5) at transplantation to 2.0 (1.0–5) at last follow-up(p=0.000). Six patients remained neurological stable compared between the time of transplantation and last follow-up. There were 7 patients were in activity group. Of which, five patients had experience of neurological relapse during the follow-up period. However, the EDSS at relapse was lower than pre-transplantation, as well as the interval time between active events was longer than pre-transplantation. The low doses steroid relieved the symptoms in clinical. It seems to back to relapse and remission phase. There are two patients experienced neurological deterioration within 7 months after transplantation and need further immnosuppression treatment. The confirmed active-free survival rate was 79.14% and progression-free survival rate was 94.12% at 83 months according to Kaplan and Meier survival curve. Median remission-lasting time reached 63 months (95%CI 52–74). It was a significant difference compared with 7 months (95%CI 6–7) of pre-transplantation (P=0.000). We compared disease activity with attacking interval time, disease duration, patient’s age and EDSS of pre-transplantation. There is a relationship between active-free event and attacking interval time, OR=5.454, P=0.01(95% CI: 1.499 to 19.844,) and without relationship with duration of disease (OR=1.009, p=0.758), patient’s age (OR=1.136, P=0.147 and EDSS (OR=1.178, p=0.864) before transplantation. Conclusions ASCT with conditioning regimen of BEAM were able to improve or stabilize of neurological manifestations in most of progressive MS patients with failure of conventional therapy in long-term. The disease activitivy of post transplantation has a relationship with attacking interval time of pre-transplantation.