***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 
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    Input: BACKGROUND Systemic sclerosis ( SSc , scleroderma ) in either its diffuse or limited skin forms has a high mortality when vital organs are affected . No treatment has been shown to influence the outcome or significantly affect the skin score , though many forms of immunosuppression have been tried . Recent developments in haemopoietic stem cell transplantation ( HSCT ) have allowed the application of profound immunosuppression followed by HSCT , or rescue , to autoimmune diseases such as SSc . METHODS Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported . Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form , with some clinical overlap . Median age was 41 years with a 5:1 female to male ratio . The skin score was > 50 % of maximum in 20/33 ( 61 % ) patients , with some lung disease attributable to SSc in 28/37 ( 76 % ) , the forced vital capacity being < 70 % of the predicted value in 18/36 ( 50 % ) . Pulmonary hypertension was described in 7/37 ( 19 % ) patients and renal disease in 5/37 ( 14 % ) . The Scl-70 antibody was positive in 18/32 ( 56 % ) and the anticentromere antibody in 10 % of evaluable patients . Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor , alone or in combination . Thirty eight patients had ex vivo CD34 stem cell selection , with additional T cell depletion in seven . Seven conditioning regimens were used , but six of these used haemoimmunoablative doses of cyclophosphamide + /- anti-thymocyte globulin + /- total body irradiation . The median duration of follow up was 12 months ( 3–55 ) . RESULTS An improvement in skin score of > 25 % after transplantation occurred in 20/29 ( 69 % ) evaluable patients , and deterioration in 2/29 ( 7 % ) . Lung function did not change significantly after transplantation . One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT , and the pulmonary hypertension did not progress in the evaluable cases . Disease progression was seen in 7/37 ( 19 % ) patients after HSCT with a median period of 67 ( range 49–255 ) days . Eleven ( 27 % ) patients had died at census and seven ( 17 % ) deaths were considered to be related to the procedure ( direct organ toxicity in four , haemorrhage in two , and infection/neutropenic fever in one ) . The cumulative probability of survival at one year was 73 % ( 95 % CI 58 to 88 ) by Kaplan-Meier analysis . CONCLUSION Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin 's lymphoma , the marked impact on skin score , a surrogate marker of mortality , the trend towards stabilisation of lung involvement , and lack of other treatment alternatives justify further carefully design ed studies . If future trials incorporate inclusion and exclusion criteria based on this preliminary experience , the predicted procedure related mortality should be around 10 % Systemic sclerosis ( SSc ) is a multisystem disease of presumed autoimmune pathogenesis for which no proven effective treatment exists . High-dose immunosuppressive therapy ( HDIT ) has been proposed as an investigational treatment for severe autoimmune diseases . Nineteen patients with poor-prognosis SSc underwent HDIT . The median age was 40 years ( range , 23 - 61 years ) , the median modified Rodnan skin score ( a measure of dermal sclerosis ) was 31 , and the median DLCO was 57 % . Conditioning therapy involved 800 cGy total body irradiation ( TBI ) ( + /- lung shielding to approximately 200 cGy ) , 120 mg/kg cyclophosphamide , and 90 mg/kg equine antithymocyte globulin . CD34-selected granulocyte-colony-stimulating factor-mobilized autologous blood stem cells provided hematopoietic rescue . With median follow-up at 14.7 months , the Kaplan-Meier estimated 2-year survival rate was 79 % . Three patients died of treatment complications and one of disease progression . Two of the first 8 patients had fatal regimen-related pulmonary injury , a complication not found among 11 subsequent patients who received lung shielding for TBI . Overall , internal organ functions were stable to slightly worse after HDIT , and 4 patients had progressive or nonresponsive disease . As measured by modified Rodnan skin scores and modified health assessment question naire disability index ( mHAQ-DI ) scores , significant disease responses occurred in 12 of 12 patients evaluated at 1 year after HDIT . In conclusion , though important treatment-related toxicities occurred after HDIT for SSc , modifications of initial approaches appear to reduce treatment risks . Responses in skin and mHAQ-DI scores exceed those reported with other therapies , suggesting that HDIT is a promising new therapy for SSc that should be evaluated in prospect i ve r and omized studies In 1997 , the first consensus guidelines for  haematopoietic SCT ( HSCT ) in autoimmune diseases ( ADs ) were published , while an international coordinated clinical programme was launched . These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation ( EBMT ) AD Registry . Subsequently , retrospective analyses and prospect i ve phase I/II studies generated evidence to support the feasibility , safety and efficacy of HSCT in several types of severe , treatment-resistant ADs , which became the basis for larger-scale phase II and III studies . In parallel , there has also been an era of immense progress in biological therapy in ADs . The aim of this document is to provide revised and up date d guidelines for both the current application and future development of HSCT in ADs in relation to the benefits , risks and health economic considerations of other modern treatments . Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres . A need for prospect i ve interventional and non-interventional studies , where feasible , along with systematic data reporting , in accordance with EBMT policies and procedures , is emphasized BACKGROUND Despite current therapies , diffuse cutaneous systemic sclerosis ( scleroderma ) often has a devastating outcome . We compared myeloablative CD34 + selected autologous hematopoietic stem‐cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma . METHODS We r and omly assigned adults ( 18 to 69 years of age ) with severe scleroderma to undergo myeloablative autologous stem‐cell transplantation ( 36 participants ) or to receive cyclophosphamide ( 39 participants ) . The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months : death , event‐free survival ( survival without respiratory , renal , or cardiac failure ) , forced vital capacity , the score on the Disability Index of the Health Assessment Question naire , and the modified Rodnan skin score . RESULTS In the intention‐to‐treat population , global rank composite scores at 54 months showed the superiority of transplantation ( 67 % of 1404 pairwise comparisons favored transplantation and 33 % favored cyclophosphamide , P=0.01 ) . In the per‐ protocol population ( participants who received a transplant or completed ≥9 doses of cyclophosphamide ) , the rate of event‐free survival at 54 months was 79 % in the transplantation group and 50 % in the cyclophosphamide group ( P=0.02 ) . At 72 months , Kaplan – Meier estimates of event‐free survival ( 74 % vs. 47 % ) and overall survival ( 86 % vs. 51 % ) also favored transplantation ( P=0.03 and 0.02 , respectively ) . A total of 9 % of the participants in the transplantation group had initiated disease‐modifying antirheumatic drugs ( DMARDs ) by 54 months , as compared with 44 % of those in the cyclophosphamide group ( P=0.001 ) . Treatment‐related mortality in the transplantation group was 3 % at 54 months and 6 % at 72 months , as compared with 0 % in the cyclophosphamide group . CONCLUSIONS Myeloablative autologous hematopoietic stem‐cell transplantation achieved long‐term benefits in patients with scleroderma , including improved event‐free and overall survival , at a cost of increased expected toxicity . Rates of treatment‐related death and post‐transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation . ( Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health ; Clinical Trials.gov number , NCT00114530 . OBJECTIVES This study describes clinical characteristics , prognostic factors , and quality of life in patients with newly diagnosed ( incident ) digital ulcers ( DU ) . METHODS Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR data base ( 22 centres in 10 countries ) . Data were collected from medical charts and during one prospect i ve visit between 01/2004 and 09/2010 . RESULTS Median age at DU diagnosis was 51 years , majority of patients were female ( 88 % ) , and limited cutaneous SSc was the most common subtype ( 61 % ) . At incident DU diagnosis , 41 % of patients had one DU and 59 % had ≥2 DU ; at the prospect i ve visit 52 % had DU . Pulmonary arterial hypertension ( PAH ) and multiple DU at diagnosis were associated with presence of any DU at the prospect i ve visit ( odds ratios : 4.34 and 1.32 ) . During the observation period ( median follow-up was 2 years ) 127 patients had ≥1 hospitalisation . The event rate of new DU per person-year was 0.66 , of DU-associated complications was 0.10 , and of surgical or diagnostic procedures was 0.12 . At the prospect i ve visit , patients with ≥1 DU reported impairment in daily activities by 57 % , those with 0 DU by 37 % . The mean difference between patients with or without DU in the SF-36 physical component was 2.2 , and in the mental component 1.4 . DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids . CONCLUSIONS This real world cohort demonstrates that DU require hospital admission , and impair daily activity . PAH and multiple DU at diagnosis were associated with future occurrence of DU Summary . Haematopoietic stem cell transplantation ( HSCT ) has been proposed for refractory autoimmune diseases , including systemic sclerosis ( SSc ) . A sequential Bayesian phase I – II clinical trial was conducted in SSc patients to assess the feasibility , the tolerance and the efficacy of autologous HSCT . Peripheral blood stem cells ( PBSC ) were collected using cyclophosphamide ( 4 g/m2 ) and recombinant human granulocyte colony‐stimulating factor ( 5 µg/kg/d ) and reinfused after positive CD34 + selection . Conditioning used cyclophosphamide ( 200 mg/kg ) or melphalan ( 140 mg/m2 ) according to cardiac function . The main end‐point was the failure of the procedure , defined by failure of either PBSC mobilization , CD34 + selection or intensification procedure , or by procedure‐related death . Among the 12 enrolled patients , three failures occurred : one PBSC mobilization , one CD34 + selection and one CD34 + intensification . Probability of graft failure was estimated at 0·286 ( 95 % confidence interval : 0·095–0·54 ) . Autologous PBSC ( n = 10 ) or bone marrow ( n = 1 ) transplantation was actually performed in 11 patients with one procedure‐related death . Median time to neutrophil ( > 0·5 × 109/l ) and platelet ( > 25 × 109/l ) haematopoietic reconstitution was 12 and 10 d respectively . After 18 months ( range 1–26 ) , eight out of 11 patients have shown major or partial response  . Non‐myeloablative conditioning , followed by a T cell‐depleted autologous PBSC or bone marrow transplantation , appears feasible with low toxicity in severe SSc with short‐term clinical benefits More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis ( SSc ) . A phase 2 single-arm study of high-dose immunosuppressive therapy ( HDIT ) and autologous CD34-selected hematopoietic cell transplantation ( HCT ) was conducted in 34 patients with diffuse cutaneous SSc .  HDIT included total body irradiation ( 800 cGy ) with lung shielding , cyclophosphamide ( 120 mg/kg ) , and equine antithymocyte globulin ( 90 mg/kg ) . Neutrophil and platelet counts were 
    Output:
    
AHSCT in severe SSc patients is associated with significant and durable improvement in physical