***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: 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 High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS . We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy  with either in vitro or in vivo T cell depletion . Median EDSS and SNRS scores at the time of inclusion were 6.5 ( 6.5–7.5 ) and 56 ( 44–65 ) , respectively . PBPC mobilisation was safe with no serious adverse effects , and without significant aggravation of disability . One patient improved significantly ( by 1.0 point on EDSS ) after the mobilisation . Two mobilisation failures were observed . No life-threatening events occurred during the transplantation . All grafted patients , except one , at least stabilised their disability status . One patient improved significantly ( by 1.5 points on EDSS ) , two patients improved slightly ( by 0.5 points on EDSS ) , one patient worsened by 1.0 point on the EDSS in 10 months . Improvement occurred with a delay of 2–4 months . Median EDSS and SNRS of grafted patients at the last follow up were 6.5 ( 5.5–8.5 ) and 64 ( 39–73 ) , respectively with median follow-up of 8.5 months . Further follow-up is needed to determine the disease course after complete immune reconstitution . Bone Marrow Transplantation ( 2000 ) 25 , 525–531 Clinical trials have indicated that autologous hematopoietic stem cell transplantation ( HSCT ) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis ( MS ) , but the mechanism has remained unclear . To underst and whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire , we examined the long-term immune reconstitution in patients with MS who received HSCT .  After numeric recovery of leukocytes , at 2-yr follow-up there was on average a doubling of the frequency of naive CD4 + T cells at the expense of memory T cells . Phenotypic and T cell receptor excision circle ( TREC ) analysis confirmed a recent thymic origin of the exp and ed naive T cell subset . Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy . These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT  does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment IMPORTANCE Most patients with relapsing-remitting ( RR ) multiple sclerosis ( MS ) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability . High-dose immunosuppressive therapy ( HDIT ) with autologous hematopoietic cell transplant ( HCT ) may , in contrast , induce sustained remissions in early MS . OBJECTIVE To evaluate the safety , efficacy , and durability of MS disease stabilization through 3 years after HDIT/HCT . DESIGN , SETTING , AND PARTICIPANTS Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis ( HALT-MS ) is an ongoing , multicenter , single-arm , phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling . Participants are evaluated through 5 years after HCT . This report is a prespecified , 3-year interim analysis of the trial . Thirty-six patients with RRMS from referral centers were screened ; 25 were enrolled . INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34 + selected ; the participants then received high-dose treatment with carmustine , etoposide , cytarabine , and melphalan as well as rabbit antithymocyte globulin before autologous HCT . MAIN OUTCOMES AND MEASURES The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes : ( 1 ) confirmed loss of neurologic function , ( 2 ) clinical relapse , or ( 3 ) new lesions observed on magnetic resonance imaging . Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events . RESULTS Grafts were collected from 25 patients , and 24 of these individuals received HDIT/HCT . The median follow-up period was 186 weeks ( interquartile range , 176 - 250 ) weeks ) . Overall event-free survival was 78.4 % ( 90 % CI , 60.1%-89.0 % ) at 3 years . Progression-free survival and clinical relapse-free survival were 90.9 % ( 90 % CI , 73.7%-97.1 % ) and 86.3 % ( 90 % CI , 68.1%-94.5 % ) , respectively , at 3 years . Adverse events were consistent with expected toxic effects associated with HDIT/HCT , and no acute treatment-related neurologic adverse events were observed . Improvements were noted in neurologic disability , quality -of-life , and functional scores . CONCLUSIONS AND RELEVANCE At 3 years , HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function . Treatment was associated with few serious early complications or unexpected adverse events BACKGROUND Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression . We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis ( MS ) who had not responded to treatment with interferon beta . METHODS Eligible patients had relapsing-remitting MS , attended Northwestern Memorial Hospital , and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months , or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse .  Peripheral blood haemopoietic stem cells were mobilised with 2 g per m2 cyclophosphamide and 10 microg per kg per day filgrastim . The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin . Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation . We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation . FINDINGS Between January , 2003 , and February , 2005 , 21 patients were treated .  Engraftment of white blood cells and platelets was on median day 9 ( range day 8 - 11 ) and patients were discharged from hospital on mean day 11 ( range day 8 - 13 ) . One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster . Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with st and ard therapy . 17 of 21 patients ( 81 % ) improved by at least 1 point on the Kurtzke exp and ed disability status scale ( EDSS ) , and five patients ( 24 % ) relapsed but achieved remission after further immunosuppression . After a mean of 37 months ( range 24 - 48 months ) , all patients were free from progression ( no deterioration in EDSS score ) , and 16 were free of relapses . Significant improvements were noted in neurological disability , as determined by EDSS score ( p<0.0001 ) , neurological rating scale score ( p=0.0001 ) , paced auditory serial addition test ( p=0.014 ) , 25-foot walk ( p<0.0001 ) , and quality of life , as measured with the short form-36 ( SF-36 ) question naire ( p<0.0001 ) . INTERPRETATION Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits , but these results need to be confirmed in a r and omised trial High-dose immunosuppressive therapy ( HDIT ) with autologous hematopoietic stem cell transplantation ( AHSCT ) is a promising approach to treatment of  multiple sclerosis ( MS ) patients . In this paper , we present the long-term outcomes of a prospect i ve single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients : mean age—35 years old ; male/female—39/60 ; median Exp and ed Disability Status Scale ( EDSS ) = 3.5 ; 43 relapsing/remitting MS , 56 progressive MS . No transplant-related deaths were observed . The mobilization and transplantation procedures were well tolerated . At 6 months post-transplant , neurological improvement or stabilization was observed in all the patients except one . Cumulative incidence of disease progression was 16.7 % at 8 years after HDIT + AHSCT .  Estimated event-free survival at median follow-up of 48.9 months was 80 % : 83.3 % in relapsing/remitting MS vs 75.5 % in progressive MS . Sixty-four patients who did not progress during the first 3 years post-transplant and were monitored for more than 3 years were included in long-term outcome analysis . At the median long-term follow-up of 62 months , 47 % of patients improved by at least 0.5 points on the EDSS scale as compared to baseline and exhibited improvement during the entire period of follow-up ; 45 % of patients were stable . No active , new , or enlarging lesions on magnetic resonance imaging were registered in patients without disease progression . AHSCT was accompanied by a significant improvement in patient ’s quality of life . Due to the fact that patient selection was quite different to the other studies and that the information about disease activity prior in the disease course and its treatment was inhomogeneous , comparison with the results in the literature should be done with caution . Thus , the risk/benefit ratio of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in our population of MS patients is very favorable . The consistency of our long-term clinical and quality of life results , together with the persistence of improvement , is in favor of the efficacy and safety of this treatment approach in MS patients OBJECTIVE To explore the safety and effectiveness of high-dose cyclophosphamide ( HiCy ) without bone marrow transplantation in patients with aggressive multiple sclerosis ( MS ) . DESIGN A 2-year open-label trial of patients with aggressive relapsing-remitting multiple sclerosis ( RRMS ) given an immunoablative regimen of HiCy ( 50 mg/kg/d for 4 consecutive days ) with no subsequent immunomodulatory therapy unless disease activity reappeared that required rescue therapy . SETTING The Johns Hopkins University Multiple Sclerosis Center , Baltimore , Maryl and . Patients A total of 21 patients with RRMS were screened for eligibility and 9 patients were enrolled in the trial . Patients were required to have 2 or more gadolinium-enhancing lesions on each of 2 pretreatment magnetic resonance imaging scans , at least 1 clinical exacerbation in the 12 months prior to HiCy treatment , or a sustained increase of 1.0 point or higher on the Exp and ed Disability Status Scale ( EDSS ) in the preceding year . Intervention Patients received 50 mg/kg/d of cyclophosphamide intravenously for 4 consecutive days 
    Output:
    
However , meta-regression analysis did not find the source of heterogeneity in which the publication country and follow up time were the influencing factors .
Available evidence suggests some clinical benefits of HCT combined with immunotherapy on MS .