***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: Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab ( Nuvion ) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease ( GVHD ) . We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD . Eighty-two percent of the participants had visceral involvement , and 86 % had overall grade III or IV acute GVHD at study entry . The respective complete and overall response rates were 14 % and 32 % at 42 days . Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects . Seventeen received rituximab , and no fatal lymphoproliferative disorders were observed . Survival at 180 days was 32 % ( 95 % confidence interval , 18%-46 % ) . The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD Daclizumab , a humanized monoclonal IgG1 directed against the alpha chain of the interleukin-2 receptor ( IL-2R ) , is a competitive inhibitor of IL-2 on activated lymphocytes . To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease ( GVHD ) might ameliorate the process , we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab . The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1 , 8 , 15 , 22 , and 29 . On day 43 , the complete response ( CR ) rate was 29 % ( 95 % confidence interval [ CI ] , 13%-51 % ) . Survival on day 120 was 29 % ( 95 % CI , 13%-51 % ) . A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1 , 4 , 8 , 15 , and 22 . For these patients , the CR rate on day 43 was 47 % ( 95 % CI , 24%-71 % ) , and survival on day 120 was 53 % ( 95 % CI , 29%-76 % ) . There were no infusion-related reactions and no serious side effects related to daclizumab . Following treatment , there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 ( + ) 25(+ ) lymphocytes , but these changes were not predictive of response . Daclizumab has substantial activity for the treatment of acute GVHD , and the second regimen evaluated is recommended for a controlled study . ( Blood , 2000 ; 95:83 - 89 BACKGROUND Severe graft-versus-host disease ( GVHD ) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells .  Mesenchymal stem cells modulate immune responses in vitro and in vivo . We aim ed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation . METHODS Patients with steroid-resistant , severe , acute GVHD were treated with mesenchymal stem cells , derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure , in a multicentre , phase II experimental study . We recorded response , transplantation-related deaths , and other adverse events for up to 60 months ' follow-up from infusion of the cells . FINDINGS Between October , 2001 , and January , 2007 , 55 patients were treated . The median dose of bone-marrow derived mesenchymal stem cells was 1.4x10(6 ) ( min-max range 0.4 - 9x10(6 ) ) cells per kg bodyweight . 27 patients received one dose , 22 received two doses , and six three to five doses of cells obtained from HLA-identical sibling donors ( n=5 ) , haploidentical donors ( n=18 ) , and third-party HLA-mismatched donors ( n=69 ) . 30 patients had a complete response and nine showed improvement . No patients had side-effects during or immediately after infusions of mesenchymal stem cells .  Response rate was not related to donor HLA-match . Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin . Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response ( 11 [ 37 % ] of 30 vs 18 [ 72 % ] of 25 ; p=0.002 ) and higher overall survival 2 years after haemopoietic-stem-cell transplantation ( 16 [ 53 % ] of 30 vs four [ 16 % ] of 25 ; p=0.018 ) . INTERPRETATION Infusion of mesenchymal stem cells exp and ed in vitro , irrespective of the donor , might be an effective therapy for patients with steroid-resistant , acute GVHD HE EFFICACY and safety of mycophenolate mofetil ( MMF ) in combination with CyA and Prednisolone for the treatment of acute and chronic GVHD ( aGVHD and cGVHD respectively ) after BMT and PBSCT from HLA mismatched and matched donors was evaluated in an open single center trial . Thirty patients , with aGVHD ( n 5 21 ) and cGVHD ( n 5 9 ) were treated with 2 g MMF  daily in addition to Cyclosporin A ( CyA ) and Prednisolone . The control group consisted of 21 patients with aGVHD ( n 5 14 ) and cGVHD ( n 5 7 ) treated with Predniosolone and CyA only .  Acute GVHD prophylaxis consisted of a combination of MTX , CyA , and Prednisolone .  Overall grade improvement of aGVHD was found in 15/21 ( 71 % ) patients treated with MMF and was significantly different compared to the control group . MMF therapy in the treatment of cGVHD lead to moderate improvement in 4 of 8 patients with limited cGVHD . The most common adverse hematologic events of MMF were leukopenia ( n 5 6 ) , anemia ( n 5 4 ) , and thrombocytopenia ( n 5 5 ) . Haematological adverse events were not severe and did not require the discontinuation of MMF . Similar to the study group , leukopenia was found in 4 of the 21 control patients , anemia in 1/21 , and thrombocytopenia in 8/21 patients . In addition , 33 % of the patients in the control group developed severe adverse effects due to Prednisolone therapy , which were not observed in the MMF group . In this preliminary study , we have shown that MMF can be used safely for the treatment of aGVHD . In addition , the MMF therapy result ed in a significant dose reduction of Prednisolone  for the treatment of GVHD when compared to a control group of patients . Treatment for GvHD after allogeneic related and unrelated BMT is one of the most critical elements in the reduction of transplant related morbidity and mortality 1 . High incidence of aGVHD indicates that more effective therapy and prevention of this severe complication is needed . MMF is a potent , uncompetitive , reversible inhibitor of eucaryotic inosine monophosphate dehydrogenase and is successfully used in the prevention of acute rejection in renal allograft recipients . 2 However , very little is known about the effect of MMF in prevention or treatment of GVHD in experimental animals . 3 The aim of our study was to evaluate the safety and efficacy of MMF in the treatment of aGVHD and cGVHD in patients after allogeneic BMT .  PATIENTS AND METHODS This study included 30 patients given a sibling transplant BM or PBSCT ( n 5 12 ; four of which were HLA mismatched ) as well as allogeneic MUD BM or PBSCT ( n 5 18 ; three of which were HLA mismatched ) . Of these patients , 19 had AML , 7 had CML , and 4 had ALL . The conditioning regimens included TBI and CY in 24/30 patients . A BU/VP16 regimen was used in 3 patients . The control group included 21 patients given allogeneic familiar BM ( n 5 8 , 3 of which were HLA mismatched ) or allogeneic MUD BM ( n 5 13 , 3 of which were HLA mismatched ) . As many variables as possible were matched between the control patients and the patients receiving MMF in the following order of priority : diagnosis , disease phase at transplant , patient age 6 5 years , and type of BMT . Of these patients , 7 had AML , 11 had CML , and 3 had ALL . The conditioning regimens in the control group of patients included TBI and CY in 17/21 patients . A BU/CY regimen was used in 2 patients , and a BU/VP16 regimen was used in 2 patients BACKGROUND AND OBJECTIVES Tumor necrosis factor a is one of the principal cytokines involved in the pathogenesis of acute graft-versus-host-disease ( GVHD ) . Infliximab is an antibody to this cytokine . DESIGN AND METHODS We performed a retrospective analysis to evaluate the activity of infliximab in 32 patients with severe steroid-refractory acute GVHD . The patients received a median of 3 weekly courses of infliximab . The main organs involved in the patients were skin ( n=2 ) liver ( n=1 ) , bowel ( n=19 ) , liver and bowel at the same stage ( n=10 ) . RESULTS Nineteen out 32 patients ( 59 % ) responded to infliximab with 6 ( 19 % ) complete and 13 ( 40 % ) partial responses . Age younger than 35 years , intestinal involvement and a longer time between hematopoietic stem cell transplantation and infliximab administration were factors predicting a favorable response . Infective episodes developed in 23/32 ( 72 % ) patients . All the 13 unresponsive patients died of GVHD shortly after infliximab . Thirteen of 19 responsive patients were alive at a median follow-up of 449 days ( range 155 - 842 ) after infliximab , with no signs of chronic GVHD ( n=5 ) , limited ( n=5 ) or extensive involvement ( n=3 ) . Six patients who responded subsequently died , one of chronic lung GVHD , the others of vascular complications or infections ( 2 fungal diseases ) . INTERPRETATION AND CONCLUSIONS We conclude that infliximab is active in the treatment of severe steroid-refractory acute GVHD , particularly when the intestine is involved . Infections commonly followed its administration . The clinical activity of infliximab and the possibility that it increases the risk of infections are worth investigating in prospect i ve trials Background . Mesenchymal stem cells ( MSC ) have immunomodulatory effects . The aim was to study the effect of MSC infusion on graft-versus-host disease ( GVHD ) . Methods . We gave MSC to eight patients with steroid-refractory grade s III-IV GVHD and one who had extensive chronic GVHD . The MSC dose was median 1.0 ( range 0.7 to 9) × 106/kg . No acute side-effects occurred after the MSC infusions . Six patients were treated once and three patients twice . Two patients received MSC from HLA-identical siblings , six from haplo-identical family donors and four from unrelated mismatched donors . Results . Acute GVHD disappeared completely in six of eight patients . One of these developed cytomegalovirus gastroenteritis . Complete resolution was seen in gut ( 6 ) , liver ( 1 ) and skin ( 1 ) . Two died soon after MSC treatment with no obvious response . One of them had MSC donor DNA in the colon and a lymph node . Five patients are still alive between 2 months and 3 years after the transplantation . Their survival rate was significantly better than that of 16 patients with steroid-resistant biopsy-proven gastrointestinal GVHD , not treated with MSC during the same period ( P=0.03 ) . One patient treated for extensive chronic GVHD showed a transient response in the liver , but not in the skin and he died of Epstein-Barr virus lymphoma . Conclusion . MSC is a very promising treatment for severe steroid-resistant acute GVHD This trial evaluated the feasibility and efficacy of the infusion of mesenchymal stem cells exp and ed using human serum for the treatment of refractory acute or chronic graft-versus-host disease . Twenty-eight expansions were started . In 22 , a minimum of more than 1x106 mesenchymal stem cells/kg were obtained after a median of 26 days ; this threshold was not obtained in the remaining cases . Ten patients received cells for the treatment of refractory or relapsed acute graft-versus-host disease and 8 for chronic disease . One patient treated for acute graft-versus-host disease obtained a complete response , 6 had a partial response and 3 did not respond . One of the chronic patients achieved complete remision , 3 a partial response , and 4 did not respond 
    Output:
    
Age , skin involvement , lower aGVHD grade , and the number of infusions are the main prognostic factors affecting the efficacy of MSC therapy for steroid-refractory aGVHD