***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: PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia ( AML ) in the last two decades . Improving induction treatment may improve the rate and quality of remission and consequently survival . In our previous trial , in younger patients , we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin ( GO ) to induction chemotherapy . PATIENTS AND METHODS Untreated patients with AML or high-risk myelodysplastic syndrome ( median age , 67 years ; range , 51 to 84 years ) were r and omly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine , with ( n = 559 ) or without ( n = 556 ) GO 3 mg/m(2 ) on day 1 of course one of therapy . The primary end point was overall survival ( OS ) . RESULTS The overall response rate was 69 % ( complete remission [ CR ] , 60 % ; CR with incomplete recovery [ CRi ] , 9 % ) , with no difference between GO ( 70 % ) and no GO ( 68 % ) arms . There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO . With median follow-up of 30 months ( range , 5.5 to 54.6 months ) , 3-year cumulative incidence of relapse was significantly lower with GO ( 68 % v 76 % ; hazard ratio [ HR ] , 0.78 ; 95 % CI , 0.66 to 0.93 ; P = .007 ) , and 3-year survival was significantly better ( 25 % v 20 % ; HR , 0.87 ; 95 % CI , 0.76 to 1.00 ; P = .05 ) . The benefit was apparent across subgroups . There was no interaction with other treatment interventions . A meta- analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse ( HR , 0.82 ; 95 % CI , 0.72 to 0.93 ; P = .002 ) and OS ( HR , 0.88 ; 95 % CI , 0.79 to 0.98 ; P = .02 ) . CONCLUSION Adding GO ( 3 mg/m(2 ) ) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin ( GO ; Mylotarg ) in children with acute myeloid leukemia ( AML ) . The NOPHO-AML 2004 protocol studied postconsolidation r and omization to GO or no further therapy . GO was administered at 5 mg/m(2 ) and repeated after 3 weeks . We r and omized 120 patients ; 59 to receive GO .  Survival was analyzed on an intention-to-treat basis . The median follow-up for patients who were alive was 4.2 years . Children who received GO showed modest elevation of transaminase and bilirubin without signs of veno-occlusive disease . Severe neutropenia followed 95 % and febrile neutropenia 40 % of the GO courses . Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred . Relapse occurred in 24 and 25 of those r and omized to GO or no further therapy . The median time to relapse was 16 months versus 10 months ( nonsignificant ) . The 5-year event-free survival and overall survival was 55 % versus 51 % and 74 % versus 80 % in those r and omized to receive GO or no further therapy , respectively . Results were similar in all subgroups . In conclusion , GO therapy postconsolidation as given in this trial was well tolerated , showed a nonsignificant delay in time to relapse , but did not change the rate of relapse or survival ( clinical trials.gov identifier NCT00476541 ) The treatment of older patients with acute myeloid leukaemia , who are not considered suitable for conventional intensive therapy , is unsatisfactory . Low-dose Ara-C(LDAC ) has been established as superior to best supportive care , but only benefits the few patients who enter complete remission . Alternative or additional treatments are required to improve the situation . This r and omised trial compared the addition of the immunoconjugate , gemtuzumab ozogamicin ( GO ) , at a dose of 5 mg on day 1 of each course of LDAC , with the intention of improving the remission rate and consequently survival .  Between June 2004 and June 2010 , 495 patients entered the r and omisation . The addition of GO significantly improved the remission rate ( 30 % vs 17 % ; odds ratio(OR ) 0.48 ( 0.32–0.73 ) ; P=0.006 ) , but not the 12 month overall survival ( 25 % vs 27 % ) . The reason for the induction benefit failing to improve OS was two-fold : survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm . Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival . Maintaining remission in older patients remains elusive We conducted a retrospective analysis of 968 adults with acute myeloid leukemia ( AML ) on 5 recent Southwest Oncology Group trials to underst and how the nature of AML changes with age . Older study patients with AML presented with poorer performance status , lower white blood cell counts , and a lower percentage of marrow blasts . Multidrug resistance was found in 33 % of AMLs in patients younger than age 56 compared with 57 % in patients older than 75 . The percentage of patients with favorable cytogenetics dropped from 17 % in those younger than age 56 to 4 % in those older than 75 . In contrast , the proportion of patients with unfavorable cytogenetics increased from 35 % in those younger than age 56 to 51 % in patients older than 75 . Particularly striking were the increases in abnormalities of chromosomes 5 , 7 , and 17 among the elderly . The increased incidence of unfavorable cytogenetics contributed to their poorer outcome , and , within each cytogenetic risk group , treatment outcome deteriorated markedly with age . Finally , the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy . The distinct biology and clinical responses seen argue for age-specific assessment s when evaluating therapies for AML Improving outcomes in older adults with acute myeloid leukemia remains a formidable challenge . Lintuzumab ( SGN-33 ; HuM195 ) is a humanized monoclonal antibody directed against CD33 , which is expressed on the majority of myeloblasts in acute myeloid leukemia . The primary objective of this r and omized , double-blinded , placebo-controlled trial was to determine whether addition of lintuzumab to low-dose cytarabine would increase overall survival in adults aged 60 years and over with untreated acute myeloid leukemia . R and omization was stratified by age , previous hematologic disorder , and performance status . All patients received cytarabine ( 20 mg subcutaneously twice daily ) on Days 1 - 10 of each 28-day cycle . Patients received lintuzumab ( 600 mg ) or placebo intravenously once weekly in Cycle 1 and once every other week in Cycles 2 - 12 . A total of 211 patients ( 107 lintuzumab , 104 placebo ) were r and omized . Median age was 70 years ( range 60 - 90 ) .  Survival was not significantly prolonged with lintuzumab treatment ( hazard ratio 0.96 ; 95 % confidence interval ( CI ) 0.72 - 1.28 ; P=0.7585 ) . Median survival was similar between treatment arms ( 4.7 months lintuzumab vs. 5.1 months placebo ) and in the subgroup of patients with high-risk cytogenetics ( 4.5 months ) . Infusion-related reactions , predominantly Grade s 1 - 2 , occurred more commonly in the lintuzumab arm ( 51 % vs. 7 % placebo ) ; no other clinical ly significant difference in safety was noted . These results confirm that lintuzumab in combination with low-dose cytarabine did not prolong survival and that low-dose cytarabine remains a valid comparator for trials of non-intensive therapies in older patients with acute myeloid leukemia , regardless of cytogenetic profile In older patients with acute myeloid leukemia ( AML ) , the prevention of relapse has remained one of the major therapeutic challenges , with more than 75 % relapses after complete remission . The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin ( GO ) has shown antileukemic remission induction activity in patients with relapsed AML . Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were r and omized between 3 cycles of  GO ( 6 mg/m(2 ) every 4 weeks ) or no postremission therapy ( control ) to assess whether GO would improve outcome . The 2 treatment groups ( 113 patients receiving GO vs 119 control patients ) were comparable with regard to age ( 60 - 78 years , median 67 years ) , performance status , and cytogenetics . A total of 110 of 113 received at least 1 cycle of GO , and 65 of 113 patients completed the 3 cycles . Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse . Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days . Nonhematologic toxicities were mild overall , but there was 1 toxic death caused by liver failure . There were no significant differences between both treatment groups with regard to relapse probabilities , nonrelapse mortality , overall survival , or disease-free survival ( 17 % vs 16 % at 5 years ) . Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points . The HOVON-43 study is registered at The Netherl and s Trial Registry ( number NTR212 ) and at http://www.controlled-trials.com as IS RCT N77039377 PURPOSE Antibody-directed chemotherapy for acute myeloid leukemia ( AML ) may permit more treatment to be administered without escalating toxicity . Gemtuzumab ozogamicin ( GO ) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope . We previously established that it is feasible to combine GO with conventional chemotherapy . We now report a large r and omized trial testing the addition of GO to induction and /or consolidation chemotherapy in untreated younger patients . PATIENTS AND METHODS In this open-label trial , 1,113 patients , predominantly younger than age 60 years , were r and omly assigned to receive a single dose of GO ( 3 mg/m(2 ) ) on day 1 of induction course 1 with one of the following three induction schedules : daunorubicin and cytarabine ; cytarabine , daunorubicin , and etoposide ; or fludarabine , cytarabine , granulocyte colony-stimulating factor , and idarubicin . In remission , 948 patients were r and omly assigned to GO in course 3 in combination with amsacrine , cytarabine , and etoposide or high-dose cytarabine . The primary end points were response rate and survival . RESULTS The addition of GO was well tolerated with no significant increase in toxicity . There was no overall difference in response or survival in either induction of consolidation . However , a predefined analysis by cytogenetics showed highly significant interaction with induction GO ( P = .001 ) , with significant survival benefit for patients with favorable cytogenetics , no benefit for patients with poor-risk disease , and a trend for benefit in intermediate-risk patients . An internally vali date d prognostic index identified approximately 70 % of patients with a predicted benefit of 10 % in 5-year survival . CONCLUSION A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity Two hundred eighty-five patients , median age 42 , with PML-RARα-positive acute promyelocytic leukaemia were r and omised to Ara-C-containing ‘ Medical Research Council ( MRC ) Chemotherapy’+ATRA ( All-trans-retinoic acid ) or anthracycline+ATRA ( modified ‘ Spanish ’ ) therapy  . MRC treatment comprised four courses with ATRA in courses 1–2 . Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1–3 . In course 3 patients were r and omised to gemtuzumab ozogamicin ( GO ) or not . The Spanish arm received 24-month maintenance . Patients were sequentially molecularly monitored . Quality of life was assessed at baseline , 3 , 6 , 9 , 12 , 24 months . Remission rates were similar in both arms ( 93 % ) : cumulative incidence of haematological relapse ( CIHR ) was 6 % at 
    Output:
    
GO has a potent clinical ly detectable anti-leukaemic effect .