***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: Purpose Azacitidine is st and ard , first-line therapy in higher-risk myelodysplastic syndromes ( MDS ) . Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates ( ORRs ) to azacitidine is not known . Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that r and omly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia ( CMML ) 1:1:1 to azacitidine ( 75 mg/m2/day on days 1 to 7 of a 28-day cycle ) ; azacitidine plus lenalidomide ( 10 mg/day on days 1 to 21 ) ; or azacitidine plus vorinostat ( 300 mg twice daily on days 3 to 9 ) . The primary phase II end point was improved ORR . Results Of 277 patients from 90 centers , 92 received azacitidine  , 93 received azacitidine plus lenalidomide , and 92 received azacitidine plus vorinostat .  Median age was 70 years ( range , 28 to 93 years ) , 85 patients ( 31 % ) were female , and 53 patients ( 19 % ) had CMML .  Serious adverse events were similar across arms , although combination-arm patients were more likely to undergo non protocol -defined dose modifications ( P < .001).With a median follow-up of 23 months ( range , 1 to 43 months ) , the ORR was 38 % for patients receiving azacitidine , 49 % for azacitidine plus lenalidomide ( P = .14 v azacitidine ) , and 27 % for azacitidine plus vorinostat ( P = .16 v azacitidine ) . For patients with CMML , ORR was higher for azacitidine plus lenalidomide versus azacitidine ( 68 % v 28 % , P = .02 ) but similar for all arms across cytogenetic subgroups , as was remission duration and overall survival . ORR was higher with mutations in DNMT3A and lower for SRSF2 , whereas ORR duration improved with fewer mutations . Lenalidomide dose reduction was associated with worse overall survival ( hazard ratio , 1.30 ; P = .05 ) . Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy , although patients with CMML benefitted from azacitidine plus lenalidomide . The efficacy of combination regimens may have been affected by dose modifications 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 Lenalidomide and azacitidine each have activity in myelodysplastic syndromes ( MDS ) patients , where both microenvironment and cell-regulatory mechanisms contribute to disease pathogenesis . The objective of this multicenter , phase 2 expansion trial was to determine the efficacy and safety of combination therapy with azacitidine ( 75 mg/m(2)/d for 5 days ) and lenalidomide ( 10 mg/d for 21 days ; 28-day cycle ) in patients with higher-risk MDS . Among 36 patients enrolled ( 18 phase 1 , 18 phase 2 ) , median age was 68 years ( range , 47 - 78 years ) and follow-up was 12 months ( range , 3 - 55 years ) . IPSS categories included intermediate-1 ( n = 5 patients with excess blasts ) , intermediate-2 ( 20 ) , and high ( 11 ) . Common grade 3/4 nonhematologic adverse events included febrile neutropenia ( 22 % of patients ) , other infection ( 11 % ) , pulmonary ( 11 % ) , cardiac ( 11 % ) , constitutional ( 11 % ) , and dermatologic ( 11 % ) . The overall response rate ( per modified MDS International Working Group criteria ) was 72 % : 16 patients ( 44 % ) achieved a complete response ( CR ) , and 10 ( 28 % ) had hematologic improvement . Median CR duration was 17 + months ( range , 3 - 39 + ) ; median overall survival was 37 + months ( range , 7 - 55 + ) for CR patients , and 13.6 months for the entire cohort ( range , 3 - 55 ) . TET2/DNMT3A/IDH1/2 mutational status was associated with response in a limited number of patients . The lenalidomide/azacitidine combination is well-tolerated and highly active in treating greater-risk MDS There are limited treatment options for older patients with acute myeloid leukemia and prognosis of these patients remains poor , thereby warranting development of novel therapies . We evaluated the efficacy and safety of azacitidine in combination with lenalidomide as front-line therapy for older patients with acute myeloid leukemia . Patients ≥60 years of age with untreated acute myeloid leukemia received azacitidine 75 mg/m2 for 7 days followed by escalating doses of lenalidomide daily for 21 days starting on day 8 of each cycle every 6 weeks . Patients received continued therapy until disease progression , unacceptable toxicity , or completion of 12 cycles . Forty-two patients ( median age , 74 years ) were enrolled with equal distribution according to European LeukemiaNet risk . The overall response rate was 40 % ( rate of complete remission with or without complete recovery of blood counts = 28 % ) . The median time to complete remission with or without complete recovery of blood counts was 12 weeks , and duration of this status was 28 weeks ( range , 4 - > 104 weeks ) . Therapy-related acute myeloid leukemia and a high score on the Hematopoietic Cell Transplantation Comorbidity Index were negative predictors of response . Early death was noted in 17 % of patients . Grade s ≥ 3 toxicities were uncommon and most adverse events were gastrointestinal , fatigue and myelosuppression . In conclusion , a sequential combination of azacitidine plus lenalidomide has clinical activity in older patients with acute myeloid leukemia , and further studies of this combination are underway . This study is registered at www . clinical trials.gov as # NCT00890929 Background 5-Azacitidine administered as a 7-day dosing regimen ( 7–0 - 0 ) is approved in high risk IPSS myelodysplastic syndrome ( MDS ) patients . Alternative regimens such as a 5-day ( 5–0 - 0 ) or 7-day with a weekend break ( 5–2 - 2 ) are commonly used . No r and omized controlled trial has been done directly comparing all three dosing regimens . The objective of this study was to compare the efficacies of the 5–0 - 0 , 5–2 - 2 , and 7–0 - 0 regimens in MDS and AML . Methods A systematic review was conducted using MEDLINE , EMBASE and CENTRAL . Eligible studies were r and omized controlled trials ( RCTs ) , observational prospect i ve and retrospective studies . The primary clinical outcomes were Objective Response Rate ( ORR ) defined as the sum of complete response ( CR ) , partial response ( PR ) , and hematological improvement ( HI ) as defined by the IWG 2006 criteria . A meta- analysis of simple proportions was conducted using a r and om effects model with weights defined according to Laird and Mosteller . Comparisons between groups were not attempted due to the heterogeneity of study design s. Results The only RCT directly comparing alternative azacitidine regimens showed no difference in ORR between the 5–0 - 0 and 5–2 - 2 regimens . All other RCTs compared a dosing regimen to conventional care . The pooled proportion of ORR was 44.8 % with 95 % CI ( 42.8 % , 45.5 % ) for 7–0 - 0 , 41.2 % with 95 % CI ( 39.2 % , 41.9 % ) for 5–0 - 0 , and 45.8 % with 95 % CI ( 42.6 % , 46.4 % ) for 5–2 - 2 . Conclusions Indirect comparison of alternative azacitidine dosing regimens in MDS and AML shows a benefit for the 7-day regimen in attaining ORR . Additional RCTs are required to definitively address this comparison Azacitidine treatment is effective in higher risk MDS ( HR-MDS ) , with less than 50 % response , lasting 2 years . Aza and lenalidomide ( Len ) have a potential synergistic effect . ViLen-01 phase IIa trial includes 6-month induction ( Aza 75 mg/m2/day , days 1–5 , Len 10 mg/day , days 6–21 , every 28 days ) , 6-month consolidation ( Aza 75 mg/m2/day , days 1–5 , every 28 days ) , and 12-month maintenance ( Len 10 mg/day , days 1–21 , every 28 days ) . Response was evaluated according to IWG criteria . Totally , 25 patients enrolled , with an average of 76.3 years old ( 60–87 ) , and 88 % with major comorbidities . Thirteen patients completed induction , 7 proceeded for consolidation , and 2 for maintenance . The overall response rate ( ORR ) was 72 % ( 18/25 ) , with 6 ( 24 % ) for CR , 3 ( 12 % ) for marrow CR , and 9 ( 36 % ) for hematologic improvement ( HI ) . The 7 non-responding patients were on the study 3 days to 4.1 months . At 6 months , 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del ( 5q ) at diagnosis . Adverse events ( AEs ) were as expected in these patients : grade s III – IV , mainly hematologic — thrombocytopenia ( 20 patients ) and neutropenia ( 13 patients ) . The common non-hematologic AEs were infections ( 14 patients ) , nausea ( 7 ) , vomiting ( 7 ) , diarrhea ( 7 ) , and skin reactions ( 5 ) . The median progression-free survival ( PFS ) was 12 ± 1.36 months , with median overall survival ( OS ) of 12 ± 1.7 months . Quality of life ( FACT question naire ) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high ( 72 % ) response rate and a reasonable expected safety profile but a relatively short PFS and OS BACKGROUND Severe , often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion . We investigated whether lenalidomide ( CC5013 ) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder . METHODS One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily . Hematologic , bone marrow , and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis . RESULTS Among the 148 patients , 112 had a reduced need for transfusions ( 76 % ; 95 % confidence interval [ CI ] , 68 to 82 ) and 99 patients ( 67 % ; 95 % CI , 59 to 74 ) no longer required transfusions , regardless of the karyotype complexity . The response to lenalidomide was rapid ( median time to response , 4.6 weeks ; range , 1 to 49 ) and sustained ; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up . The maximum hemoglobin concentration reached a median of 13.4 g per deciliter ( range , 9.2 to 18.6 ) , with a corresponding median rise of 5.4 g per deciliter ( range , 1.1 to 11.4 ) , as compared with the baseline nadir value before transfusion . Among 85 patients who could be evaluated , 62 had cytogenetic improvement , and 38 of the 62 had a complete cytogenetic remission . There was complete resolution of cytologic abnormalities in 38 of 106 patients whose serial bone marrow sample s could be evaluated . Moderate-to-severe neutropenia ( in 55 % of patients ) and thrombocytopenia ( in 44 % ) were the most common reasons for interrupting 
    Output:
    
Conclusions : The current study may serve as a preliminary data to suggest that the addition of LEN may offer incremental benefit to patients with high-risk MDS , AML and CMML .