***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To evaluate clinical outcomes of autologous peripheral blood stem cell transplantation ( APBCST ) between opticospinal multiple sclerosis ( OSMS ) and conventional multiple sclerosis ( CMS ) during disease progressive stage in a Chinese population . Thirty-six secondary progressive MS patients , among whom 21 were with OSMS and 15 with CMS , underwent APBSCT and were followed up for an average of 48.92 months ( range , 10–91 months ) . Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor . Modified BEAM conditioning regimen ( Tiniposide , melphalan , carmustin , and cytosine arabinoside ) were administered . Outcomes were evaluated using the exp and ed disability status scale ( EDSS ) . No maintenance treatment was administered if there was no disease progression . No treatment-related mortality occurred . Among the 36 patients , one OSMS patient dropped during the follow-up . Among the 22 relapse-free patients , 20 were with continuous neurological improvement without any relapse events , and two remained in neurologically stable states . Among the 13 relapse patients , seven had experienced of neurological relapse , but with no progression during the follow-up period ; and six experienced neurological deterioration after transplantation and needed further immunosuppressant treatment . The confirmed relapse-free survival rate was 62.9 % and progression-free survival rate was 83.3 % after 91 months according to Kaplan and Meier survival curves . Eleven of the 20 OSMS patients ( 55 % ) and two of the 15 CMS patients ( 13.3 % ) stayed in disease active group ( P = 0.014 ) . For the 20 OSMS patients , the overall EDSS score decreased significantly after transplantation ( P = 0.016 ) , while visual functions had no significant improvement ( P = 0.716 ) . Progressive OSMS has a higher relapse rate than CMS following APBSCT The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy ( HDIT ) followed by autologous hematopoietic cell transplantation ( AHCT ) in advanced multiple sclerosis ( MS ) .  TBI , CY and antithymocyte globulin were followed by transplantation of autologous , CD34-selected PBSCs . Neurological examinations , brain magnetic resonance imaging and cerebrospinal fluid ( CSF ) for oligoclonal b and s ( OCB ) were serially evaluated . Patients ( n=26 , mean Exp and ed Disability Status Scale (EDSS)=7.0 , 17 secondary progressive , 8 primary progressive , 1 relapsing/remitting ) were followed for a median of 48 months after HDIT followed by AHCT . The 72-month probability of worsening ⩾1.0 EDSS point was 0.52 ( 95 % confidence interval , 0.30–0.75 ) . Five patients had  an EDSS at baseline of ⩽6.0 ; four of them had not failed treatment at last study visit . OCB in CSF persisted with minor changes in the b and ing pattern . Four new or enhancing lesions were seen on MRI , all within 13 months of treatment . In this population with high baseline EDSS , a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant . Non-inflammatory events may have contributed to neurological worsening after treatment . HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS BACKGROUND Strong immunosuppression , including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation ( aHSCT ) , has been used to treat patients with multiple sclerosis , improving control of relapsing disease . We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis . METHODS We did this phase 2 single-arm trial at three hospitals in Canada . We enrolled patients with multiple sclerosis , aged 18 - 50 years with poor prognosis , ongoing disease activity , and an Exp and ed Disability Status Scale of 3.0 - 6.0 .  Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim . Immunoablation with busulfan , cyclophosphamide , and rabbit anti-thymocyte globulin was followed by aHSCT . The primary outcome was multiple sclerosis activity-free survival ( events were clinical relapse , appearance of a new or Gd-enhancing lesion on MRI , and sustained progression of Exp and ed Disability Status Scale score ) . This study was registered at Clinical Trials.gov , NCT01099930 . FINDINGS Between diagnosis and aHSCT , 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans . Median follow-up was 6.7 years ( range 3.9 - 12.7 ) . The primary outcome , multiple sclerosis activity-free survival at 3 years after transplantation was 69.6 % ( 95 % CI 46.6 - 84.2 ) . With up to 13 years of follow-up after aHSCT , no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans . The rate of brain atrophy decreased to that expected for healthy controls . One of 24 patients died of transplantation-related complications . 35 % of patients had a sustained improvement in their Exp and ed Disability Status Scale score . INTERPRETATION We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs . Furthermore , many of the patients had substantial recovery of neurological function despite their disease 's aggressive nature . FUNDING Multiple Sclerosis Scientific Research Foundation Objective : To evaluate the safety , efficacy , and durability of multiple sclerosis ( MS ) disease stabilization after high-dose immunosuppressive therapy ( HDIT ) and autologous hematopoietic cell transplantation ( HCT ) . Methods : High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis ( HALT-MS ) is a phase II clinical trial of HDIT/HCT  for patients with relapsing-remitting ( RR ) MS who experienced relapses with disability progression ( Exp and ed Disability Status Scale [ EDSS ] 3.0–5.5 ) while on MS disease-modifying therapy .  The primary endpoint was event-free survival ( EFS ) , defined as survival without death or disease activity from any one of : disability progression , relapse , or new lesions on MRI . Participants were evaluated through 5 years posttransplant . Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events ( AE ) . Results : Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT . Median follow-up was 62 months ( range 12–72 ) . EFS was 69.2 % ( 90 % confidence interval [ CI ] 50.2–82.1 ) . Progression-free survival , clinical relapse-free survival , and MRI activity-free survival were 91.3 % ( 90 % CI 74.7%–97.2 % ) , 86.9 % ( 90 % CI 69.5%–94.7 % ) , and 86.3 % ( 90 % CI 68.1%–94.5 % ) , respectively . AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted . Improvements were noted in neurologic disability with a median change in EDSS of −0.5 ( interquartile range −1.5 to 0.0 ; p = 0.001 ) among participants who survived and completed the study . Conclusion : HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years . Clinical Trials.gov identifier : NCT00288626 . Classification of evidence : This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT Since the start of the international stem cell transplantation project in 1997 , over 2000 patients have received a haematopoietic stem cell transplant ( HSCT )  , mostly  autologous  , as treatment for a severe autoimmune disease , the majority being multiple sclerosis ( MS ) , systemic sclerosis ( SSc ) and Crohn 's disease . There was an overall 85 % 5-year survival and 43 % progression-free survival . Around 30 % of patients in all disease subgroups had a complete response , often durable despite full immune reconstitution . In many cases , e.g. systemic sclerosis , morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented , beyond any predicted known effects of intense immunosuppression alone . It is hoped that the results of the three running large prospect i ve r and omized controlled trials will allow modification of the protocol s to reduce the high transplant-related mortality which relates to regimen intensity , age of patient , and comorbidity . Mesenchymal stromal cells ( MSC ) , often incorrectly called stem cells , have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade . Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies , few r and omised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far . This could be due to confusion in cell product terminology , complexity of clinical study design and execution or agreement on meaningful outcome measures . Within the rheumatic diseases , SLE and rheumatoid arthritis ( RA ) have received most attention . Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome ; one single centre comparative study in 172 RA was positive . In addition , small numbers of patients with Crohn 's disease , multiple sclerosis , primary Sjögren 's disease , polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically . The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed Background Autologous haematopoietic stem cell transplantation ( HSCT ) is a viable option for treatment of  aggressive multiple sclerosis ( MS ) .  No r and omised controlled trial has been performed , and thus , experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy . In this observational study , we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS . Methods Neurologists from the major hospitals in Sweden filled out a follow-up form with prospect ively collected data . Fifty-two patients were identified in total ; 48 were included in the study and evaluated for safety and side effects ; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome . In this cohort , 34 patients ( 83 % ) had relapsing-remitting MS , and mean follow-up time was 47 months . Results At 5 years , relapse-free survival was 87 % ; MRI event-free survival 85 % ; exp and ed disability status scale ( EDSS ) score progression-free survival 77 % ; and disease-free survival ( no relapses , no new MRI lesions and no EDSS progression ) 68 % . Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome ( disease-free survival 79 % vs 46 % , p=0.028 ) . There was no mortality . The most common long-term side effects were herpes zoster reactivation ( 15 % ) and thyroid disease ( 8.4 % ) . Conclusions HSCT is a very effective treatment of  inflammatory active MS  and can be performed with a high degree of safety at experienced centres Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases , we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy ( BEAM regimen ) followed by autologous blood stem cell rescue and antithymocyte globulin . Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- ( or GM- ) CSF . In 9 cases , additional CD34 + cell- selection of the graft was performed . Here we up date previously published results of this novel treatment , mainly with regard to clinical efficacy , as the median follow-up time has reached 40 months ( range , 21–51 ) . Infections were the principal toxicity early after the procedure , with death of a patient from aspergillosis 65 days post stem cell infusion . No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34 + cell-depleted graft . Mild and transient neurotoxicity was observed in 10 patients ( 42 % ) , most probably associated with fever and infections . Eighteen patients ( 18/23 ; 78 % ) responded to the treatment , i.e. , they were improved or stabilized , while five patients progressed , of which 4 had primary progressive disease . Of those improved or stabilised ( 18 ) , 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression , although their disability scores have not 
    Output:
    
Conclusions This meta- analysis provides evidence s that AHSCT can induce long-term remissions for MS patients with a high degree of safety .
We indicate low- and intermediate-intensity regimens and RRMS patients with the presence of Gd+ lesions at baseline MRI can obtain the optimal benefit/risk ratio from AHSCT