***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: Newly diagnosed patients with acute graft-versus-host disease ( GvHD , grade s I-IV ; n = 211 ) were given 6-methylprednisolone ( 6MPred ) 2 mg/kg per day for 5 consecutive days ; 150 patients ( 71 % ) tapered 6MPred on day + 5 and were considered responders ; 61 patients ( 29 % ) could not taper their steroid dose and were considered nonresponders . The cumulative incidence of transplant-related mortality ( TRM ) for responders and nonresponders is , respectively , 27 % and 49 % ( P = .009 ) , and the 5-year survival is 53 % and 35 % ( P = .007 ) . Nonresponders on day + 5 ( n = 61 ) were r and omized to receive 6MPred 5 mg/kg per day for 10 days alone ( n = 34 ) or in combination with rabbit anti-thymocyte globulin ( ATG , 6.25 mg/kg in 10 days ; n = 27 ) . The 2 groups were balanced for clinical and GvHD characteristics . One month after r and omization , 26 % had a complete response ; 23 % , a partial response ; 33 % , stable GvHD ; 10 % , worsened ; and 8 % , died . There was no significant difference in response , TRM , and survival between the non-ATG and ATG group . In conclusion , 5 days of prednisolone as first-line therapy of acute GvHD identifies patients with different risk of TRM , and second-line therapy with a combination of 6MPred + ATG does not improve patient outcome , compared with 6MPred alone SUMMARY Patients with hematological malignancies undergoing allogeneic marrow transplantation from HLA-identical siblings were entered into a r and omized study to determine whether the prophylactic administration of horse anti-human thymocyte globulin ( ATG ) would decrease the incidence or severity of graft-versus-host disease ( GVHD ) . Patients were conditioned with high-dose cyclophosphamide and total body irradiation before grafting and received methotrexate after grafting . When marrow engraftment was documented ( median 16.5 days after transplantation ) , patients were r and omized either to receive or not to receive horse ATG , 7 mg/kg , i.v . , every other day for six doses . Twenty-nine patients received ATG and 27 patients did not . Both groups were comparable with respect to diagnoses , disease status , age , sex , donor-recipient sex match , and supportive care . Administration of ATG was associated with fever and chills in most patients , but was otherwise well tolerated . Patients receiving ATG had no delay in recovery of peripheral granulocyte or platelet counts , did not require increased platelet support , and did not have more infectious complications . No significant difference in either incidence or severity of GVHD was noted between patients receiving and those not receiving prophylactic ATG , although GVHD , if it developed , tended to be less severe among patients receiving ATG .  Survival and causes of death were also comparable between groups . Thus , administration of horse ATG after documentation of marrow engraftment in recipients of HLA-identical allogeneic marrow grafts had neither significant toxicity nor beneficial effect BACKGROUND Graft-versus-host disease ( GVHD ) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors .  Anti-T-cell globulins ( ATGs ) might lower the incidence of GVHD . We did a prospect i ve , r and omised , multicentre , open-label , phase 3 trial to compare st and ard GVHD prophylaxis with ciclosporin and methotrexate with or without anti-Jurkat ATG-Fresenius ( ATG-F ) . METHODS Between May 26 , 2003 , and Feb 8 , 2007 , 202 patients with haematological malignancies were central ly r and omly assigned using computer-generated centre-stratified block r and omisation between treatment groups receiving ciclosporin and methotrexate with or without additional ATG-F. One patient in the ATG-F group did not undergo transplantation , thus 201 patients who underwent transplantation with peripheral blood ( n=164 ; 82 % ) or bone marrow ( n=37 ; 18 % ) grafts from unrelated donors after myeloablative conditioning were included in the full analysis set , and were analysed according to their r and omly assigned treatment ( ATG-F n=103 , control n=98 ) . The primary endpoint was severe acute GVHD ( aGVHD ) grade III-IV or death within 100 days of transplantation . The trial is registered with the numbers DRKS00000002 and NCT00655343 . FINDINGS The number of patients in the ATG-F group who had severe aGVHD grade III-IV or who died within 100 days of transplantation was 12 and 10 ( 21.4 % , 95 % CI 13.4 - 29.3 ) , respectively , compared with 24 and nine ( 33.7 % , 24.3 - 43.0 ) patients , respectively , in the control group ( adjusted odds ratio 0.59 , 95 % CI 0.30 - 1.17 ; p=0.13 ) . The cumulative incidence of aGVHD grade III-IV was 11.7 % ( 95 % CI 6.8 - 19.8 ) in the ATG-F group versus 24.5 % ( 17.3 - 34.7 ) in the control group ( adjusted hazard ratio [ HR ] 0.50 , 95 % CI 0.25 - 1.01 ; p=0.054 ) , and cumulative incidence of aGVHD grade II-IV was 33.0 % ( n=34 ; 95 % CI 25.1 - 43.5 ) in the ATG-F group versus 51.0 % ( n=50 ; 95 % CI 42.0 - 61.9 ) in the control group ( adjusted HR 0.56 , 0.36 - 0.87 ; p=0.011 ) . The 2-year cumulative incidence of extensive chronic GVHD was 12.2 % ( n=11 ; 95 % CI 7.0 - 21.3 ) versus 42.6 % ( n=34 ; 95 % CI 33.0 - 55.0 ; adjusted HR 0.22 , 0.11 - 0.43 ; p<0.0001 ) . There were no differences between treatment groups with regard to relapse , non-relapse mortality , overall survival , and mortality from infectious causes . INTERPRETATION The addition of ATG-F to GVHD prophylaxis with ciclosporin and methotrexate result ed in decreased incidence of acute and chronic GVHD without an increase in relapse or non-relapse mortality , and without compromising overall survival . The use of ATG-F is safe for patients who are going to receive a haematopoietic cell transplantation from matched unrelated donors . FUNDING Fresenius Biotech Summary : In total , 94 patients with homozygous beta thalassemia were r and omized to two different conditioning regimens : busulfan 600 mg/m2+cyclophosphamide 200 mg/kg or busulfan 16 mg/kg+cyclophosphamide 200 mg/kg and antilymphocyte globulin ( 47 in each group ) , for bone marrow transplantation , to see whether increased myeloablation or increased immunosuppression would reduce rejection .  Busulfan pharmacokinetics in determining outcome was evaluated . There was no significant difference in engraftment , graft-versus-host disease , rejection , and overall and disease-free survival in the two groups . Systemic exposure to  busulfan was significantly higher in the 600 mg/m2 group , but in both groups there was a wide interindividual variation in the busulfan kinetics . Six patients  rejected the graft , two in the busulfan 600 mg group and four in busulfan 16 mg group ( P=0.677 CI −0.17 , 0.07 ) , but in five patients ( pharmacokinetic data not available in one patient ) who rejected the graft busulfan first dose trough level ( Cmin-1 ) was below 150 ng/ml while it was above this level in the 66 of 68 patients with successful engraftment ( P⩽0.001 ) . This r and omized trial shows that rejection is influenced by busulfan levels and suggests that monitoring of busulfan levels and dose adjustment based on first-dose kinetics may reduce the risk of rejection We have previously shown that hemopoietic stem cell transplant ( HSCT ) recipients can be stratified on day+7 as having low , intermediate or a high risk of transplant-related mortality ( TRM ) . With the aim of reducing TRM and GVHD , intermediate and high-risk patients ( n=170 ) were r and omized to receive anti-thymocyte globulin ( ATG , thymoglobuline ) on day+7 ( n=84 ) or no treatment ( n=86 ) ( controls ) . There was a reduction of TRM from 35 % in controls to 29 % in ATG patients ( P=0.3 ) , of acute GVHD III – IV from 15 to 5 % ( P=0.02 ) and of chronic GVHD from 26 to 11 % ( P=0.03 ) ; survival was comparable . The predictive value of the day+7 score on TRM was confirmed for controls ( 19 vs 42 % for intermediate vs high risk , respectively , P=0.03 ) , whereas ATG abrogated this predictive effect ( 29 vs 29 % ) . ATG  reduced GVHD ( P=0.006 ) in high-risk patients , but not in patients with an intermediate risk . In conclusion , we confirm that TRM can be predicted on the basis of day+7 laboratory values , after alternative donor HSCT ; in high- , but not intermediate-risk patients , the administration of ATG on day+7 reduces GVHD . These results may represent a platform for risk-adapted post transplant immune modulation One hundred nine patients with hematologic malignancies , undergoing bone marrow transplants ( BMT ) from unrelated donors , were r and omized in 2 consecutive trials to receive or not to receive antithymocyte globulin ( ATG ) in the conditioning regimen , as follows : ( A ) 54 patients ( median age , 28 years ; 39 % with advanced disease ) were r and omized to no ATG  ( n = 25 ) versus  7.5 mg/kg rabbit ATG ( Thymoglobulin ; Sangstat , Lyon , France ) ( n = 29 ) ; ( B ) 55 patients ( median age , 31 years , 71 % with advanced disease ) were r and omized to no ATG ( n = 28 ) versus 15 mg/kg rabbit ATG ( n = 27 ) . Grade III-IV graft-versus-host disease ( GVHD ) was diagnosed in 36 % versus 41 % ( P = .8 ) in the first and in 50 % versus 11 % ( P = .001 ) in the second trial . Transplant-related mortality ( TRM ) , relapse , and actuarial 3-year survival rates were comparable in both trials . In fact , despite the reduction of GVHD in the second trial , a higher risk for lethal infections ( 30 % vs 7 % ; P = .02 ) was seen in the arm given 15 mg/kg ATG .  Extensive chronic GVHD developed overall more frequently in patients given no ATG ( 62 % vs 39 % ; P = .04 ) , as confirmed by multivariate analysis ( P = .03 ) . Time to 50 x 10(9)/L platelets was comparable in the first trial ( 21 vs 24 days ; P = .3 ) and delayed in the ATG arm in the second trial ( 23 vs 38 days ; P = .02 ) . These trials suggest that ( 1 ) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD , ( 2 ) this does not translate to a reduction in TRM because of the increased risk for infections , and ( 3 ) though survival is unchanged , extensive chronic GVHD is significantly reduced in patients receiving ATG Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation . We performed a r and omized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease .  Thirty-five patients received methotrexate alone , and 32 received  methotrexate , antithymocyte globulin , and prednisone . Of the patients who received  methotrexate alone , 48 per cent had acute graft-versus-host disease , as compared with 21 per cent of those who received methotrexate , antithymocyte globulin , and prednisone ( P = 0.01 ) . The age of the recipient was a significant factor in the development of acute graft-versus-host disease : Older patients had a higher incidence of the disease ( P = 0.001 ) . We conclude that the combination of methotrexate , antithymocyte globulin , and prednisone significantly decreased the incidence 
    Output:
    
AUTHORS ' CONCLUSIONS Our systematic review suggests that the addition of ATG during allogeneic HSCT significantly reduces the incidence of severe grade s ( II to IV ) of acute GvHD , whereas the incidence of overall acute GVHD ( grade s I to IV ) was not significantly lowered .
This indicates a reduction of the severity but not the incidence of acute GVHD .
However , this effect did not lead to a significant improvement of overall survival , which may be due to the severe potential side effects of the consecutively increased immunosuppression .