***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: BACKGROUND In a multicenter , r and omized , open-label phase III study , patients ≥ 65 years with newly diagnosed AML  received decitabine 20 mg/m(2 ) once daily for 5 days every 4 weeks ( n = 242 ) or treatment choice ( supportive care or cytarabine 20 mg/m(2 ) once daily for 10 days every 4 weeks ; n = 243 ) .  Decitabine use demonstrated greater response rates ( P = .001 ) and OS data favored decitabine . PATIENTS AND METHODS In a post hoc sensitivity analysis of mature data of patients in the intent-to-treat population ( N = 485 ) , OS at 3 , 6 , 12 , 18 , and 24 months after r and omization was estimated for each arm using Kaplan-Meier methods . Age , cytogenetic risk , and Eastern Cooperative Oncology Group performance status were used as stratification factors in the Cox regression model to estimate the hazard ratio . RESULTS A survival advantage was seen with decitabine at each cutoff time point ; hazard ratios for OS for decitabine vs. treatment choice were 0.83 , 0.71 , 0.83 , 0.80 , and 0.79 at 3 , 6 , 12 , 18 , and 24 months , respectively . A trend toward improved OS  with decitabine was observed at fixed time points over 2 years . CONCLUSION Decitabine should be considered as a treatment option for older patients with AML and poor prognostic risk factors Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction . The incidence of Acute Myeloid Leukemia ( AML ) increases progressively with age and its treatment is challenging . This prospect i ve case control study was undertaken to compare the safety , efficacy , and cost-effectiveness of decitabine with those of cytarabine in older patients with newly diagnosed AML who are not fit for intensive chemotherapy . Material s and Methods . 30 eligible patients above 60 years old with newly diagnosed AML were assigned to receive decitabine or cytarabine . The primary end point was overall survival ( OS ) . The secondary objective was to compare adverse events and cost-effectiveness of therapy in the two study groups . Results . In this study , 15 patients received decitabine and 15 patients received cytarabine . The median OS was 5.5 months for each of the treatment groups . The hazard ratio between the treatment groups was 0.811 with 95 % CI of 0.390 to 1.687 . Toxicity profile was similar in both groups . Cost per cycle of chemotherapy in INR was 24,200 for decitabine and 1,600 for low-dose cytarabine group . Median of simplified cost-effectiveness ratio was 0.00022 for decitabine group and 0.0034 for low-dose cytarabine group . Conclusions . For elderly patients with AML , decitabine and low-dose cytarabine should be chosen based on the patient 's choice and affordability . Our study has shown that both of these agents have similar OS and toxicity . Low-dose cytarabine scores over decitabine in developing countries as it is more cost-effective We conducted an open-label phase 1 study exploring the feasibility , safety , and biologic activity of epigenetic priming with decitabine before st and ard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia ( AML ) . We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion ( Arm A ) or a continuous infusion ( Arm B ) for 3 , 5 , or 7 days before a single , st and ard induction with infusional cytarabine ( 100 mg/m² for 7 days ) and daunorubicin ( 60 mg/m² × 3 doses ) . Toxicity was similar to that of st and ard induction chemotherapy alone . Although we did not identify a maximum tolerated dose , there was more gastro-intestinal toxicity with 7 days of decitabine priming . Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+ ) bone marrow cells when decitabine was delivered by a short pulse ( Arm A ) . Twenty-seven subjects ( 90 % ) responded to therapy : 17 with  complete remission ( 57 % ) and 10 with partial remission  ( 33 % ) . Of the patients with partial remission to protocol treatment , 8 achieved remission to their next therapy , bringing the overall complete remission rate to 83 % . We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates . This trial was registered at www . clinical trials.gov as NCT00538876 Background The treatment of acute myeloid leukemia of older , medically non-fit patients still poses a highly unmet clinical need , and only few large , prospect i ve studies have been performed in this setting . Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine ( decitabine ) in myelodysplastic syndromes and acute myeloid leukemia with 20–30 % bone marrow blasts , we investigated whether this drug is also active in patients with more than 30 % blasts . Design and Methods To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy , 227 patients ( median age , 72 years ) , many with comorbidities , adverse cytogenetics and /or preceding myelodysplastic syndrome were treated with this hypomethylating agent . During the initial decitabine treatment ( 135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks ) , a median of two cycles was administered ( range , 1–4 ) . All-trans retinoic acid was administered to 100 patients during course 2 . Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses ( range , 1–19 ) with a lower dose of decitabine ( 20 mg/m2 ) infused over 1 hour on 3 consecutive days every 4–6 weeks . Results The complete and partial remission rate was 26 % , 95 % CI ( 20 % , 32 % ) , and an antileukemic effect was noted in 26 % of patients . Response rates did not differ between patients with or without adverse cytogenetics ; patients with monosomal karyotypes also responded . The median overall survival from the start of decitabine treatment was 5.5 months ( range , 0–57.5 + ) and the 1-year survival rate was 28 % , 95%CI ( 22%,34 % ) . Toxicities were predominantly hematologic . Conclusions Decitabine is well tolerated by older , medically non-fit patients with acute myeloid leukemia ;  myelosuppression is the major toxicity . The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome . Because of these encouraging results , r and omized studies evaluating single-agent decitabine versus conventional treatment are warranted . The study is registered with the German Clinical Trials Registry , number DRKS00000069 Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin ( GO ) . A total of 110 patients ( median age 70 years ; range 27–89 years ) were treated with decitabine and GO in a trial design ed on model-based futility to accommo date subject heterogeneity : group 1 : relapsed/refractory acute myeloid leukemia ( AML ) with complete remission duration ( CRD ) < 1 year ( N=28 , 25 % ) ; group 2 : relapsed/refractory AML with CRD ⩾1 year ( N=5 , 5 % ) ; group 3 : untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome ( MDS ) or untreated myelofibrosis ( MF ; N=57 , 52 % ) ; and group 4 : AML evolving from MDS or relapsed/refractory MDS or MF ( N=20 , 18 % ) . Treatment consisted of decitabine 20 mg/m2 daily for 5 days and GO 3 mg/m2 on day 5 . Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone  . Complete remission (CR)/CR with incomplete count recovery was achieved in 39 ( 35 % ) patients ; group 1= 5/28 ( 17 % ) , group 2=3/5 ( 60 % ) , group 3=24/57 ( 42 % ) and group 4=7/20 ( 35 % ) . The 8-week mortality in groups 3 and 4 was 16 % and 10 % , respectively . Common drug-related adverse events included nausea , mucositis and hemorrhage . Decitabine and GO  improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) are unclear . METHODS We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine  to identify somatic mutations and their relationships to clinical responses . Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles . We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients . An extension cohort included 32 additional patients who received decitabine in different protocol s. RESULTS Of the 116 patients , 53 ( 46 % ) had bone marrow blast clearance ( < 5 % blasts ) . Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile ( 29 of 43 patients [ 67 % ] vs. 24 of 71 patients [ 34 % ] , P<0.001 ) and among patients with TP53 mutations than among patients with wild-type TP53 ( 21 of 21 [ 100 % ] vs. 32 of 78 [ 41 % ] , P<0.001 ) . Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes . However , in this study of 10-day courses of decitabine , neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles . CONCLUSIONS Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk , TP53 mutations , or both had favorable clinical responses and robust ( but incomplete ) mutation clearance after receiving serial 10-day courses of decitabine . Although these responses were not durable , they result ed in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT01687400 . ) Novel , non-intensive treatment options in older MDS/AML patients planned for allografting , with the goal of down-staging the underlying disease and bridging time to transplantation , are presently being developed . 5-azacytidine and decitabine ( DAC ) are of particular interest , as they can be given repetitively , with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses . We describe 15 consecutive patients ( median age 69 years , range 60–75 years ) with MDS ( n=10 ) or AML ( n=5 ) who all received first-line treatment with DAC and subsequent allografting  ( from sibling donor in four patients , unrelated donor in 11 ) after reduced-intensity  conditioning with the FBM regimen .  Successful engraftment was attained in 14/15 patients , all of whom achieved a CR , with a median duration of 5 months ( range 1 + to 51 + ) . Six of these 14 patients are alive ( 4 with complete donor chimerism ) , 8 have died either from relapse ( n=4 ) or treatment-related complications while in CR ( n=4 ) . We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible , with no unexpected toxicities and appears as a valid alternative to st and ard chemotherapy ( ‘ InDACtion instead of induction ’ ) in elderly patients with MDS/AML PURPOSE Older patients with acute myeloid leukemia ( AML ) have limited treatment options because of the 
    Output:
    
Subgroup analyses of age , cytogenetics risk , AML type and bone marrow blast percentage showed no significant differences of treatment response to decitabine .
In conclusion , decitabine is an effective and well-tolerated therapeutic alternative with acceptable side effects in elderly AML patients