***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: A prospect i ve r and omized trial of therapy for severe aplastic anemia was design ed to compare early bone marrow transplantation with conventional treatments .  All patients with a sibling matched at the major histocompatibility region were transplanted . Transplantation was performed with 17 - 100 ( median 33 ) days of original diagnosis . Conventional treatments included transfusion support with or without and rogens .  Twenty-four of 36 patients intered on the transplant arm are alive after 4 - 20 ( median 9 ) mo with full marrow reconstitution . Only two are limited by chronic graft-versus-host disease . In contrast only 12 of 31 conventionally treated patients are alive . Six of these survivors have improved , five incompletely . The 19 nontransplant deaths have occurred within 1 - 11 ( median 3 ) mo of diagnosis . Compared to nontransplant regimens , early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia ( p = 0.006 ) . Pending longer follow-up , early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia Background A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60–70 % of patients with severe aplastic anemia . We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia . Design and Methods Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases  with matched clinical characteristics treated with horse anti-thymocyte globulin . Results Response rates at 3 , 6 and 12 months were similar for patients treated with rabbit anti-thymocyte globulin or horse anti-thymocyte globulin : 40 % versus 55 % ( P=0.43 ) , 45 % versus 58 % ( P=0.44 ) and 50 % versus 58 % ( P=0.61 ) , respectively . No differences in early mortality rates or overall survival were observed . We then performed multivariable analyses of response at 6 months and overall survival and identified the presence of a paroxysmal nocturnal hemoglobinuria clone ( P=0.01 ) and a pretreatment absolute reticulocyte count greater than 30 × 109/L ( P=0.007 ) as independent predictors of response and younger age ( P=0.003 ) , higher pretreatment absolute neutrophil ( P=0.02 ) and absolute lymphocyte counts ( P=0.03 ) as independent predictors of overall survival . None of the immunogenetic polymorphisms studied was predictive of response to immunosupressive therapy . Conclusions Despite reports suggesting differences in biological activity of different anti-thymocyte globulin preparations , rabbit and horse anti-thymocyte globulin appear to have a similar efficacy for up-front treatment of severe aplastic anemia . Clinical trial.gov : NCT01231841 Rabbit antithymocyte globulin ( rATG ; thymoglobulin , Genzyme ) in combination with cyclosporine , as first-line immunosuppressive therapy , was evaluated prospect ively in a multicenter , European , phase 2 pilot study , in 35 patients with aplastic anemia . Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry , treated with horse ATG ( hATG ; lymphoglobulin ) and cyclosporine . The primary end point was response at 6 months . At 3 months , no patients had achieved a complete response to rATG .  Partial response occurred in 11 ( 34 % ) . At 6 months , complete response rate was 3 % and partial response rate 37 % . There were 10 deaths after rATG ( 28.5 % ) and 1 after subsequent HSCT . Infections were the main cause of death in 9 of 10 patients . The best response rate was 60 % for rATG and 67 % for hATG . For rATG , overall survival at 2 years was 68 % , compared with 86 % for hATG ( P = .009 ) . Transplant-free survival was 52 % for rATG and 76 % for hATG ( P = .002 ) . On multivariate analysis , rATG ( hazard ratio = 3.9 , P = .003 ) and age more than 37 years ( hazard ratio = 4.7 , P = .0008 ) were independent adverse risk factors for survival . This study was registered at www . clinical trials.gov as NCT00471848 CONTEXT In most patients , aplastic anemia results from T-cell-mediated immune destruction of bone marrow . Aplastic anemia can be effectively treated by stem cell transplantation or immunosuppression . OBJECTIVE To assess long-term outcomes after immunosuppressive therapy . DESIGN , SETTING , AND PATIENTS Cohort of 122 patients ( 31 were < or = 18 years and 91 were > 18 years ) with severe aplastic anemia , as determined by bone marrow cellularity and blood cell count criteria , were enrolled in a single-arm interventional research protocol from 1991 to 1998 at a federal government research hospital . INTERVENTIONS A dose of 40 mg/kg per day of antithymocyte globulin administered for 4 days , 10 to 12 mg/kg per day of cyclosporine for 6 months ( adjusted for blood levels ) , and a short course of corticosteroids ( 1 mg/d of methylprednisolone for about 2 weeks ) . MAIN OUTCOME MEASURES Survival , improvement of pancytopenia and transfusion-independence , relapse , and evolution to other hematologic diseases . RESULTS Response rates were 60 % at 3 months after initiation of treatment , 61 % at 6 months , and 58 % at 1 year . The blood cell counts of patients who responded no longer satisfied severity criteria and they were transfusion-independent . Overall actuarial survival at 7 years was 55 % . Survival was associated with early satisfaction of response criteria ( 86 % vs 40 % at 5 years ; P<.001 ) and by blood counts at 3 months ( reticulocyte count or platelet count of > 50 x 10(3)/ microL predicted survival at 5 years of 90 % [ 64/71 ] vs 42 % [ 12/34 ] for patients with less robust recovery [ P<.001 by log-rank test ] ) . There were no deaths among responders more than 3 years after treatment . Relapse was common , but severe pancytopenia usually did not recur . Relapse did not influence survival . Thirteen patients showed evolution to other hematologic diseases , including monosomy 7 . CONCLUSIONS Approximately half of patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine have durable recovery and excellent long-term survival . These outcomes were related to the quality of hematologic recovery OBJECTIVE This study was design ed to investigate four different immunosuppressive therapy ( IST ) regimens as treatment of acquired severe aplastic anemia ( SAA ) . PATIENTS AND METHODS 142 consecutive SAA patients were r and omized to receive one of the following IST regimens : equine anti-human thymocyte immunoglobulin ( E-ATG ) alone ( IST regimen I ) ; E-ATG and cyclosporine A ( CSA ) ( IST regimen II ) ; E-ATG , CSA plus recombinant human granulocyte-macrophage colony-stimulating factor ( rhuGM-CSF ) and rhu erythropoietin ( rhuEPO ) ( IST regimen III ) ; or rabbit ATG ( ATG-F ) , CSA , rhuGM-CSF , and rhuEPO ( IST regimen IV ) . No repeated courses of E-ATG or ATG-F were given for nonresponders . All patients also received stanozolol or testosteron propionate . RESULTS The overall response rate to IST regimen I was 58 % . The response to IST regimen II ( 79 % ) was significantly higher ( p = 0.04 ) , more rapid and complete than after IST regimen I. The response rate to IST regimen IV ( 53 % ) was significantly lower than that of IST regimen III ( 73 % , p = 0.039 ) . The additional use of growth factors did not reduce early deaths and did not accelerate hematopoietic recovery after IST . Of the 142 patients enrolled in this trial , 92 ( 65 % ) are alive at a median follow-up time of 102 months ( range , 54 - 166 months ) . The 5-year actuarial survival for IST regimens I , II , III , and IV was 58 % , 81 % , 80 % , and 66 % , respectively . CONCLUSION The combination of E-ATG and CSA remains the best combination for the treatment of SAA patients , producing a survival advantage at 5 years . The addition of growth factors did not improve these results . Rabbit ATG-F appeared less effective than E-ATG BACKGROUND In severe acquired aplastic anemia , hematopoietic failure is the result of immune-mediated destruction of bone marrow stem and progenitor cells . Immunosuppressive therapy with antithymocyte globulin ( ATG ) plus cyclosporine is an effective alternative to stem-cell transplantation and improves blood counts and survival . Although horse ATG is the st and ard therapy , rabbit ATG is more potent in depleting peripheral-blood lymphocytes and is preferred in other clinical circumstances . METHODS From December 2005 through July 2010 , we performed a r and omized trial comparing these two ATG formulations in conventional regimens . Patients were treated at a single facility . The primary outcome was hematologic response at 6 months , as determined by blood counts . The study was design ed to enroll 60 patients each for the rabbit-ATG and horse-ATG groups and was powered to detect a difference of 25 percentage points in the response rate . RESULTS A large , unexpected difference was observed in the rate of hematologic response at 6 months in favor of horse ATG ( 68 % ; 95 % confidence interval [ CI ] , 56 to 80 ) as compared with rabbit ATG ( 37 % ; 95 % CI , 24 to 49 ; P<0.001 ) . Overall survival at 3 years also differed , with a survival rate of 96 % ( 95 % CI , 90 to 100 ) in the horse-ATG group as compared with 76 % ( 95 % CI , 61 to 95 ) in the rabbit-ATG group ( P=0.04 ) when data were censored at the time of stem-cell transplantation , and 94 % ( 95 % CI , 88 to 100 ) as compared with 70 % ( 95 % CI , 56 to 86 ; P=0.008 ) in the respective groups when stem-cell-transplantation events were not censored . CONCLUSIONS In a r and omized study , rabbit ATG was inferior to horse ATG as a first treatment for severe aplastic anemia , as indicated by hematologic response and survival . ( Funded by the Intramural Research Program of the National Institutes of Health ; Clinical Trials.gov number , NCT00260689 . ) We recently reported that rabbit antithymocyte globulin was markedly inferior to horse antithymocyte globulin as a primary treatment for severe aplastic anemia . Here we exp and on our findings in this unique cohort of patients .  Rabbit antithymocyte globulin was detectable in plasma for longer periods than horse antithymocyte globulin ; rabbit antithymocyte globulin in plasma retained functional capacity to bind to lymphocytes for up to 1 month , horse antithymocyte globulin for only about 2 weeks . In the first week after treatment there were much lower numbers of neutrophils in patients treated with rabbit antithymocyte globulin  than in patients receiving horse antithymocyte globulin .  Both antithymocyte globulins induced a “ cytokine storm ” in the first 2 days after administration . Compared with horse antithymocyte globulin , rabbit antithymocyte globulin was associated with higher levels of chemokine ( C-C motif ) lig and 4 during the first 3 weeks . Besides a much lower absolute number and a lower relative frequency of CD4 + T cells  , rabbit antithymocyte globulin induced higher frequencies of CD4+CD38 + , CD3+CD4−CD8− T cells , and B cells than did horse antithymocyte globulin .  Serum sickness occurred around 2 weeks after infusion of both types of antithymocyte globulin . Human anti-antithymocyte globulin antibodies , especially of the IgM subtype , correlated with serum sickness , which appeared concurrently with clearance of antithymocyte globulin in blood and with the production of cytokines . In conclusion , rabbit and horse antithymocyte globulins have very different pharmacokinetics and effects on neutrophils , lymphocyte subsets , and cytokine release . These differences may be related to their efficacy in suppressing the immune system and restoring hematopoiesis in bone marrow failure . Clinical trials.gov identifier : NCT00260689 Background Previous reports showed that outcome of rabbit antithymocyte globulin ( rATG ) was not satisf 
    Output:
    
Compared with rabbit ATG , horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA .