***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: GW395058 , a PEGylated peptide agonist of the thrombopoietin receptor , stimulates megakaryocytopoiesis and has previously been shown to increase platelet counts in vivo . The pharmacokinetics and pharmacodynamics of GW395058 were characterized using a r and omized , crossover study in a large-animal model ( dog ) of chemotherapy-induced thrombocytopenia . Nine beagle dogs received i.v . carboplatin ( 350 mg/m(2 ) ) on day 0 and day 28 . GW395058 ( 1.31 mg/kg ) ( n = 6 ) or vehicle control ( n = 3 ) was administered on day 1 and day 29 either as an i.v . bolus or s.c . injection . After i.v . administration , peak concentrations of GW395058 occurred rapidly , while the half-life averaged approximately 56 h. Bioavailability ( + /- st and ard deviation ) of GW395058 given s.c . was 78.2 % ( 20.9 % ) . GW395058 ( i.v . and s.c . ) ameliorated the platelet nadir ( p = 0.0086 ) and result ed in a shorter time to recovery compared to the control group . The mean nadir platelet counts following carboplatin administration were 197,000 cells/microl ( 80,000 ) for the i.v . GW395058-dose group , 183,000 cells/microl ( 72,000 ) for the s.c.-dose group and 71,000 cells/microl ( 38,000 ) for the vehicle-alone group . GW395058 reduced the thrombocytopenic effects of carboplatin in dogs . No GW395058-related  adverse side effects were observed We evaluated the efficacy and safety of romiplostim , a thrombopoietin mimetic , in patients with low- or intermediate-risk myelodysplastic syndromes ( MDS ) receiving azacitidine therapy . Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts ( < 50 vs ≥ 50 × 10(9)/L ) and r and omized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine . The primary endpoint was the incidence of clinical ly significant thrombocytopenic events , defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period . No formal hypothesis testing was planned . The incidence of clinical ly significant thrombocytopenic events in patients receiving romiplostim 500 μg , romiplostim 750 μg , or placebo was 62 % , 71 % , and 85 % , respectively . The incidence of platelet transfusions was 46 % , 36 % , and 69 % , respectively . These differences were not statistically significant with the small numbers in each group . Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 ( P = .0373 ) and at the nadir ( P = .0035 ) compared with  placebo . Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient ( 4 % ) . This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy Aberrant DNA methylation , which results in leukemogenesis , is frequent in patients with myelodysplastic syndromes ( MDS ) and is a potential target for pharmacologic therapy . Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters Background Lenalidomide treatment in myelodysplastic syndrome ( MDS ) may lead to thrombocytopenia and dose reductions/delays . This study evaluated the safety and tolerability of the thrombopoietin mimetic romiplostim and its effects on the incidence of clinical ly significant thrombocytopenic events ( CSTEs ) in lower risk MDS patients receiving lenalidomide . Methods Patients were assigned to weekly placebo ( n = 12 ) or romiplostim 500 μg ( n = 14 ) or 750 μg ( n = 13 ) for four 28-day lenalidomide cycles . Results The treatment groups were generally similar with respect to baseline disease characteristics . Del(5q ) abnormalities were noted in 1 ( 8 % ) patient in the placebo group , 3 ( 21 % ) in the romiplostim 500 μg group , and two ( 15 % ) in the 750 μg group . CSTEs were noted in 8 ( 67 % ) patients in the placebo group , 4 ( 29 % ) in the romiplostim 500 μg group , and 8 ( 62 % ) in the romiplostim 750 μg group . Throughout the study , median platelet counts trended lower in placebo-treated than in romiplostim-treated patients . Thrombocytopenia-related adjustments  in lenalidomide occurred in 6 ( 50 % ) patients in the placebo group , 5 ( 36 % ) in the romiplostim 500 μg group , and 2 ( 15 % ) in the 750 μg group . Although the percentages of patients who received platelet transfusions were similar across treatment groups , there was a trend toward lower numbers of transfusions in both romiplostim groups during each treatment cycle . There were two serious treatment-related adverse events during the treatment period ( cerebrovascular accident , placebo ; worsening thrombocytopenia , romiplostim 500 μg ) . Two patients ( romiplostim 500 and 750 μg , respectively ) had an increase in bone marrow blasts to > 20 % during treatment , but had no post-treatment biopsy to confirm or exclude the diagnosis of progression to AML . Conclusions These data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose reductions/delays due to thrombocytopenia . Additional study is needed to confirm the results of this preliminary trial . Trial registration Clinical Trials.gov Myelodysplastic syndrome ( MDS ) comprises a spectrum of heterogeneous diseases . Most patients present with ineffective hematopoiesis . The pathophysiology involves immune-mediated effects , cytokine dysregulation , and apoptosis , among others . We treated 14 transfusion-requiring patients with MDS , 10 with refractory anemia ( RA ) and four with RA with excess blasts ( RAEB ) with a 4-day course of antithymocyte globulin ( ATG ) followed by intermittent etanercept for 4 months . Among 13 evaluable patients , five are red blood cell and platelet transfusion independent for intervals extending beyond 2 years , and two have normalized their peripheral blood parameters . One additional patient showed a transient rise of platelet and neutrophil counts , for an overall response rate of 46 % . Responding patients showed striking improvements in marrow cell abnormalities as characterized by flow cytometry . These data show that a combination of ATG plus etanercept offers effective palliative therapy for unselected patients with MDS . Further trials incorporating these two agents are warranted Abstract Patients with myelodysplastic syndrome ( MDS ) receiving hypomethylating agents commonly develop thrombocytopenia . This double-blind study evaluated the efficacy and safety of romiplostim , a peptibody protein that increases platelets , in patients with MDS receiving decitabine . Patients  received romiplostim  750 μg ( n = 15 )  or placebo  ( n = 14 )  and decitabine  . Median platelet counts at the beginning of each decitabine cycle trended lower in placebo-treated than in romiplostim-treated patients . Bleeding events occurred in 43 % of placebo-treated and 27 % of romiplostim-treated patients , and platelet transfusions were administered to 57 % of placebo-treated and 47 % of romiplostim-treated patients . Overall clinical therapeutic response was achieved by 21 % of placebo-treated and 33 % of romiplostim-treated patients . Treatment was generally well tolerated . Progression to acute myeloid leukemia ( AML ) occurred in one patient per group . Adding romiplostim to decitabine treatment is well tolerated and may be beneficial , as indicated by trends toward higher platelet counts at the beginning of each treatment cycle and lower platelet transfusion rates and percentages of patients with bleeding events Eltrombopag ( SB-497 115 ) is a first-in-class , oral , small-molecule , nonpeptide agonist of the thrombopoietin receptor ( TpoR ) , being developed as a treatment for thrombocytopenia of various etiologies . In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects , eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5 , 10 , 25 , 30 , 50 , and 75 mg . The pharmacokinetics of eltrombopag were dose dependent and linear , and eltrombopag increased platelet counts in a dose-dependent manner . There were no apparent differences in the incidence or severity of adverse events in subjects receiving active or placebo study medication . These observations indicate that eltrombopag is a once-daily , oral TpoR agonist with demonstrated thrombopoietic activity in human subjects , encouraging further studies in patients with thrombocytopenia The objective of this study was to evaluate the tolerability , pharmacodynamics , and pharmacokinetics of AMG 531 , a novel thrombopoietin receptor lig and , after a single intravenous or subcutaneous injection in healthy subjects BACKGROUND Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options . Platelet transfusions provide transient benefit and are limited by alloimmunisation . Eltrombopag , an oral thrombopoietin receptor agonist , increases platelet counts and has pre clinical antileukaemic activity . We aim ed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome , secondary acute myeloid leukaemia after myelodysplastic syndrome , or de-novo acute myeloid leukaemia . METHODS We did this multicentre , r and omised , placebo-controlled , double-blind , phase 1/2 trial at 37 centres in ten countries in Europe , east Asia , and the Americas . Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for st and ard treatments ; had platelet counts of less than 30 × 10(9 ) platelets per L ; had 10 - 50 % bone-marrow blasts ; or were platelet transfusion dependent were r and omly assigned ( 2:1 ) , via a telephone-based interactive voice-response system ( GlaxoSmithKline Registration and Medication Ordering System ) with a permuted-block r and omisation schedule ( block size of three ) , to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg . R and omisation was stratified by presence of poor-prognosis ( complex ) karyotype ( presence of at least three abnormalities , or chromosome 7 abnormalities , vs absence ) and bone-marrow blast count ( < 20 % vs ≥20 % ) . Patients and study personnel were masked to treatment allocation . The primary endpoint was safety and tolerability , including adverse events , non-haematological laboratory grade 3 - 4 toxic effects , and changes in bone-marrow blast counts from baseline . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , number NCT00903422 . FINDINGS Between May 14 , 2009 , and May 9 , 2013 , we r and omly assigned 98 patients to receive either eltrombopag ( n=64 ) or placebo ( n=34 ) . 63 ( 98 % ) patients in the eltrombopag group and 32 ( 94 % ) patients in the placebo group had adverse events . The most common adverse events were pyrexia ( 27 [ 42 % ] vs 11 [ 32 % ] ) , nausea ( 20 [ 31 % ] vs 7 [ 21 % ] ) , diarrhoea ( 19 [ 30 % ] vs 6 [ 18 % ] ) , fatigue ( 16 [ 25 % ] vs 6 [ 18 % ] ) , decreased appetite ( 15 [ 23 % ] vs 5 [ 15 % ] ) , and pneumonia ( 14 [ 22 % ] vs 8 [ 24 % ] ) . Drug-related adverse events of grade 3 or higher were reported in six ( 9 % ) patients in the eltrombopag group and four ( 12 % ) patients in the 
    Output:
    
Treatment with TPO mimetics result ed in a lower number of MDS patients suffering from bleeding events .
There is no evidence for a difference between study groups regarding transfusion requirement .