***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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    ***EXAMPLES*** 
    Input: This phase 3 prospect i ve r and omized trial evaluated the efficacy and long-term safety of erythropoietin ( EPO ) with or without granulocyte colony-stimulating factor plus supportive care ( SC ; n = 53 ) versus SC alone ( n = 57 ) for the treatment of anemic patients with lower-risk myelodysplastic syndromes . The response rates in the EPO versus SC alone arms were 36 % versus 9.6 % , respectively , at the initial treatment step , 47 % in the EPO arm , including subsequent steps . Responding patients had significantly lower serum EPO levels ( 45 % vs 5 % responses for levels < 200 mU/mL vs > or = 200 mU/mL ) and improvement in multiple quality -of-life domains . With prolonged follow-up ( median , 5.8 years ) , no differences were found in overall survival of patients in the EPO versus SC arms ( median , 3.1 vs 2.6 years ) or in the incidence of transformation to acute myeloid leukemia ( 7.5 % and 10.5 % patients , respectively ) . Increased survival was demonstrated for erythroid responders versus nonresponders ( median , 5.5 vs 2.3 years ) . Flow cytometric analysis showed that the percentage of P-glycoprotein(+ ) CD34(+ ) marrow blasts was positively correlated with longer overall survival . In comparison with SC alone , patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses , similar survival , and incidence of acute myeloid leukemia transformation BACKGROUND The hematological and quality of life ( QoL ) changes associated with darbepoetin alfa ( DA ) therapy were assessed in anemic patients with previously untreated low- and intermediate-1-risk myelodysplastic syndrome ( MDS ) . PATIENTS AND METHODS Fifty-three patients received DA  administered subcutaneously once a week for 24 weeks . Treatment was initiated at 150 microg fixed dose and was doubled if after the first 12 weeks there was no or suboptimal erythroid response . RESULTS The final response rate was 24/53 ( 45 % ) , with 21 major and three minor responses . Most of the responses ( 21/24 ; 87.5 % ) were obtained at the dose of 150 microg . With a median follow-up of 9.4 months , 17 patients maintain their response . Treatment was well tolerated with no relevant side-effects . MDS progression was observed in one case . Increases in hemoglobin levels were positively correlated with improved QoL scores using both the linear analog scale assessment ( energy level , r = 0.429 , P = 0.036 ; daily activities , r = 0.653 , P < 0.001 ; overall well-being , r = 0.457 , P = 0.024 ) and the Functional Assessment of Cancer Therapy-Anemia question naire ( r = 0.247 , P = 0.025 ) . In multivariate analysis , only low levels ( < 200 IU/l ) of endogenous erythropoietin predicted response to DA therapy . CONCLUSIONS DA is an active , safe and well tolerated treatment for anemia in a substantial proportion of patients with low- and intermediate-1-risk MDS , and has a positive impact on the patients ' Patients with myelodysplastic syndromes ( MDS ) often develop anaemia result ing in frequent transfusions and fatigue . Darbepoetin alfa is an erythropoiesis‐stimulating agent ( ESA ) approved for treating chemotherapy‐induced anaemia . This single‐arm , phase 2 study examined the efficacy of darbepoetin alfa 500 μg every 3 weeks ( Q3W ) for treating anaemia in low‐risk MDS patients ( after 6 weeks , poor responders received darbepoetin alfa 500 μg every 2 weeks ) . The primary end‐point was the incidence of erythroid responses ( International Working Group criteria ) after 13 weeks of therapy . Secondary end‐points included the incidence of erythroid responses at weeks 28 and 55 , [ or weeks 27 and 53 for dose escalations to every two weeks ( Q2W ) ] , and safety parameters . Analyses were stratified by the patient ’s previous ESA therapy status [ ESA‐naïve ( n = 144 ) vs. prior ESA‐treated ( n = 62 ) ] . After 13 weeks of therapy , 49 % of ESA‐naïve patients and 26 % of prior ESA‐treated patients achieved a major erythroid response . After 53/55 weeks , 59 % of ESA‐naïve patients and 34 % of prior ESA‐treated patients achieved a major erythroid response ; 82 % of ESA‐naïve patients and 55 % of prior ESA‐treated patients achieved target haemoglobin of 110 g/l . Thromboembolic or related adverse events occurred in 2 % of patients ; no pulmonary embolisms were reported . In conclusion , darbepoetin alfa , 500 μg Q3W appeared well tolerated and increased haemoglobin levels in low‐risk MDS patients Abstract Background : Current guidelines support the use of erythropoiesis-stimulating agents for the treatment of anemia associated with low-risk myelodysplastic syndromes ( MDS ) . Design and methods : Single-arm , open-label , multi-center , phase 2 trial that evaluated the efficacy and safety of darbepoetin alfa ( DA ) in patients with low or intermediate-risk MDS , hemoglobin < 100 g/L , erythropoietin ( EPO ) levels < 500 IU/L and transfusion requirements < 2 units/month over the preceding 2 months . Erythroid response ( major [ MaR ] or minor [ MiR ] ) and fatigue ( Functional Assessment of Cancer Therapy – Fatigue [ FACT-F ] ) were evaluated at 8 , 16 and 24 weeks . DA was initiated at 300 μg weekly . For patients who did not achieve MaR by 8 weeks , filgrastim 300 μg weekly was added . Clinical trial registration : clinical trials.gov identifier : NCT01039350 . Results : Forty-four patients ( 72.7 % transfusion independent ) were included . Median age was 76.0 years ( range 41.3–92.4 ) , 54.5 % were male , and 90.9 % presented ECOG Status ( 0–1 ) . Eighteen patients received filgrastim . An erythroid response was achieved by 31 of 44 patients ( 70.5 % ) at week 8 ( 47.7 % MaR , 22.7 % MiR ) , 31 of 44 patients ( 70.5 % ) at week 16 ( 61.4 % MaR , 9.1 % MiR ) , and 32 of 44 patients ( 72.7 % ) at week 24 ( 61.3 % MaR , 11.4 % MiR ) . Mean ( 95 % CI ) change in FACT-F at week 24 was 3.61 ( 0.72 to 6.51 ) . Baseline EPO levels < 100 IU/L were a predictive factor of response . DA was well tolerated . Four mild ( two iron deficiencies , flu syndrome and headache ) and one fatal ( thromboembolic event ) adverse events were considered related to darbepoetin alfa . Conclusions : A fixed dose of 300 μg of darbepoetin alfa weekly ( with or without filgrastim ) seems to be an effective and safe treatment for anemic patients with low or intermediate-risk MDS , low transfusion burden and EPO levels < 500 IU/L. Results may not be extrapolable to unselected MDS patients The myelodysplastic syndromes ( MDSs ) are heterogeneous with respect to clinical characteristics , pathologic features , and cytogenetic abnormalities . This heterogeneity is a challenge for evaluating response to treatment . Therapeutic trials in MDS have used various criteria to assess results , making cross- study comparisons problematic . In 2000 , an International Working Group ( IWG ) proposed st and ardized response criteria for evaluating clinical ly significant responses in MDS . These criteria included measures of alteration in the natural history of disease , hematologic improvement , cytogenetic response , and improvement in health-related quality of life . The relevance of the response criteria has now been vali date d prospect ively in MDS clinical trials , and they have gained acceptance in research studies and in clinical practice . Because limitations of the IWG criteria have surfaced , based on practical and reported experience , some modifications were warranted . In this report , we present recommendations for revisions of some of the initial criteria Darbepoetin ( DAR ) , with or without granulocyte colony-stimulating factor ( G-CSF ) , has proved effective in treating anemia in patients with lower-risk myelodysplastic syndrome ( MDS ) , but its effects on quality of life ( QoL ) and exercise functioning are less well established . In this phase II study ( no. NCT00443339 ) , lower-risk MDS patients with anemia and endogenous erythropoietin ( EPO ) level < 500 IU/L received DAR 500 μg once every 2 weeks for 12 weeks , with G-CSF added at week 12 in non-responders . Physical performance was assessed with the 6-min walking test and , for fit patients , maximal oxygen consumption ( VO2max ) . QoL was evaluated using SF-36 and FACT-An tests . In 99 patients , erythroid response rate according to IWG 2006 criteria was 48 and 56 % at 12 and 24 weeks , respectively . Addition of G-CSF rescued 22 % of non-responders . In 48 % of the responders , interval between darbepoetin injections could be increased for maintenance treatment . Serum EPO level was the only independent predictive factor of response at 12 weeks , and its most discriminant cutoff value was 100 IU/L. QoL and VO2max showed improvement over time in responders , compared with non-responders . With a median follow-up of 52 months , median response duration was not reached , and 3-year cumulative incidence of acute myeloid leukemia and overall survival ( OS ) was 14.5 and 70 % , respectively . Baseline transfusion dependence , International Prognostic Score System ( IPSS ) , and Revised IPSS accurately predicted OS from treatment onset . Tolerance of darbepoetin was good . In conclusion , this regimen of darbepoetin every 2 weeks yielded high response rates and prolonged response duration . Objective improvement in exercise testing and in patient-reported QoL confirms the clinical relevance of anemia correction with erythropoiesis-stimulating agents To evaluate efficacy , safety , changes in biological features , and quality of life ( QoL ) in low-risk anemic patients with MDS treated with darbepoetin alfa ( DPO ) , 41 patients  received DPO 150 μg weekly for 24 weeks . The dose was increased to 300 μg weekly in non-responsive patients . During treatment , 10/17 ( 59 % ) transfusion-dependent ( TD ) and 13/23 ( 56 % ) transfusion-free ( TF ) patients responded . In TF patients , Hb increased from 9.2 ± 0.9 g/dL to 10.3 ± 1.4 g/dL by 24 weeks ( p = 0.004 ) . The mean response duration was 22 weeks ( 95 % CI : 19.7–24.0 ) in TF patients compared with 15.1 weeks ( 95 % CI : 13.3–17.5 ) in TD patients . Response to treatment was associated with increases in QoL. Decreases in the percentage of apoptotic progenitor cells ( p = 0.007 ) and CD34 + cells ( p = 0.005 ) were observed . These results confirm previous studies demonstrating the safety and efficacy  of DPO in anemic patients with MDS . Biological changes and improvement in QoL were associated with response . Adequate dosing is to be determined This Phase II study evaluated darbepoetin alfa ( DA ) in 24 patients with predominantly low or intermediate‐1 risk myelodysplastic syndrome ( MDS ) . Intra‐patient dose escalation of DA was undertaken in three 6‐week dose cohorts until a major erythroid response was achieved : 4.5 mcg/kg/week , 9 mcg/kg/week , and 9 mcg/kg/week plus granulocyte‐colony stimulating factor ( G‐CSF ) 2.5 mcg/kg twice weekly . Patients with refractory anemia with ringed sideroblasts ( RARS ) commenced DA at 9 mcg/kg/week . The weight‐based dosing regimen translated into a median starting DA dose of 390 mcg/week . Erythroid responses were observed in 16/24 patients ( 67 % ; 12 major and 4 minor ) , with a median response duration of 11 months in major responders . Addition of G‐CSF generated a major erythroid response in 7/15 patients ( 47 % ) who suboptimally responded to DA alone . DA was well tolerated , except for worsening of baseline mild hypertension and renal insufficiency in one patient with diabetes . IP 
    Output:
    
QoL , transfusion rates and haemoglobin levels improved with treatment .
This meta‐ analysis suggests that DA treatment can be useful for improving erythroid response in MDS patients with anaemia , even among patients previously treated with ESA