***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    Input: Most patients with chronic myeloid leukemia ( CML ) treated with imatinib  will relapse if treatment is withdrawn . We conducted a prospect i ve clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease ( UMRD ) by conventional quantitative polymerase chain reaction ( PCR ) on imatinib for at least 2 years . Patients stopped imatinib and were monitored frequently for molecular relapse . At 24 months , the actuarial estimate of stable treatment-free remission was 47.1 % . Most relapses occurred within 4 months of stopping imatinib , and no relapses beyond 27 months were seen . In the 21 patients treated with  interferon  before imatinib , a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk , as was slower achievement of UMRD after switching to imatinib . Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD , even several years after imatinib withdrawal . No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations ( median follow-up , 42 months ) . All patients who relapsed remained sensitive to imatinib re-treatment . These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent , sensitive molecular monitoring and early rescue of molecular relapse We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia ( CML ) . In the CA180 - 034 study , 670 patients with imatinib-resistant/-intolerant CML in chronic phase ( CML-CP ) received dasatinib 100 mg once daily , 50 mg twice daily , 140 mg once daily , or 70 mg twice daily . At 6 years , 188 ( 28 % ) of 670 patients remained on study treatment . Estimated 6-year protocol -defined progression-free survival ( PFS ) rates were 49 % , 51 % , 40 % , and 47 % , respectively , and estimated 6-year overall survival ( OS ) rates were 71 % , 74 % , 77 % , and 70 % , respectively ( intent-to-treat population , including protocol -defined progression or death after discontinuation ) . Estimated 6-year rates of survival without transformation on study treatment were 76 % , 80 % , 83 % , and 74 % , respectively . Major molecular response was achieved in 43 % ( 100 mg once daily ) and 40 % ( all other arms ) of patients by 6 years . Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS . Notably , estimated 6-year PFS rates based on ≤1 % , > 1 % to 10 % , and > 10 % BCR-ABL transcripts at 3 months were 68 % , 58 % , and 26 % , respectively . Most adverse events occurred by 2 years . Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy , particularly if achieving BCR-ABL ≤10 % at 3 months . This study was registered at Clinical Trials.gov : NCT00123474 Imatinib mesylate ( imatinib ) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia ( CML ) . Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong , patient adherence is critical . The ADAGIO ( Adherence Assessment with Glivec : Indicators and Outcomes ) study aim ed to assess prospect ively over a 90-day period the prevalence of  imatinib nonadherence in patients with CML ; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence ; and to examine whether treatment response is associated with adherence levels . A total of 202 patients were recruited from 34 centers in Belgium , of whom 169 were evaluable . One-third of patients were considered to be nonadherent . Only 14.2 % of patients were perfectly adherent with 100 % of prescribed imatinib taken . On average , patients with suboptimal response had significantly higher mean percentages of imatinib not taken ( 23.2 % , st and ard deviation [ SD ] = 23.8 ) than did those with optimal response ( 7.3 % , SD = 19.3 , P = .005 ; percentages calculated as proportions x 100 ) . Nonadherence is more prevalent than patients , physicians , and family members believe it is , and therefore should be assessed routinely . It is associated with poorer response to imatinib .  Several determinants may serve as alert signals , many of which are clinical ly modifiable We developed a module of the MD And erson Symptom Inventory ( MDASI ) for patients with chronic myeloid leukemia ( CML ) . To develop the MDASI-CML , we identified CML-specific symptoms from qualitative interviews  with 35 patients . A list of c and i date symptoms was reduced by a panel of patients , caregivers , and clinicians to the 13 core MDASI symptom items and 6 CML-specific items ; these items were subsequently administered to 30 patients . Cognitive debriefing confirmed that the items were clear , relevant , and easy to use . One additional CML-specific symptom item was added , for a total of 7 . The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year . The content , concurrent , known-group , and construct validity of the MDASI-CML were evaluated . The internal consistency and test-retest reliabilities of the module were adequate . Longitudinal analysis showed relatively stable symptom severity scores over time . The most severe symptoms were fatigue , drowsiness , disturbed sleep , muscle soreness and cramping , and trouble remembering things . Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms . The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase ( CML-CP ) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years . Patients with newly diagnosed CML-CP were r and omized to receive 100 mg dasatinib ( n = 259 ) or 400 mg imatinib ( n = 260 ) once daily . The retrospective l and mark analysis included patients evaluable at the relevant time point ( 3 , 6 , or 12 months ) . Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib . At 3 and 6 months , the proportion of patients with BCR-ABL transcript levels ≤10 % was higher in the dasatinib arm . Deeper responses at 3 , 6 , and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms . First-line dasatinib result ed in faster and deeper responses compared with imatinib . The achievement of an early molecular response was predictive of improved progression-free survival and overall survival , supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors . This study was registered at www . clinical trials.gov as NCT00481247 BACKGROUND Imatinib , a selective inhibitor of the BCR-ABL tyrosine kinase , produces high response rates in patients with chronic-phase chronic myeloid leukemia ( CML ) who have had no response to interferon alfa . We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML . METHODS We r and omly assigned 1106 patients to receive imatinib ( 553 patients ) or interferon alfa plus low-dose cytarabine ( 553 patients ) . Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met . Patients were evaluated for hematologic and cytogenetic responses , toxic effects , and rates of progression . RESULTS After a median follow-up of 19 months , the estimated rate of a major cytogenetic response ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) at 18 months was 87.1 percent ( 95 percent confidence interval , 84.1 to 90.0 ) in the imatinib group and 34.7 percent ( 95 percent confidence interval , 29.3 to 40.0 ) in the group given interferon alfa plus cytarabine ( P<0.001 ) . The estimated rates of complete cytogenetic response were 76.2 percent ( 95 percent confidence interval , 72.5 to 79.9 ) and 14.5 percent ( 95 percent confidence interval , 10.5 to 18.5 ) , respectively ( P<0.001 ) . At 18 months , the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group ( P<0.001 ) . Imatinib was better tolerated than combination therapy . CONCLUSIONS In terms of hematologic and cytogenetic responses , tolerability , and the likelihood of progression to accelerated-phase or blast-crisis CML , imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML BACKGROUND In a r and omized trial , 1106 patients with chronic myeloid leukemia ( CML ) in chronic phase were assigned to imatinib or interferon alfa plus cytarabine as initial therapy . We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission . METHODS Levels of BCR-ABL transcripts were measured by a quantitative real-time polymerase-chain-reaction assay . Results were expressed relative to the median level of BCR-ABL transcripts in the blood of 30 patients with untreated CML in chronic phase . RESULTS In patients who had a complete cytogenetic remission , levels of BCR-ABL transcripts after 12 months of treatment had fallen by at least 3 log in 57 percent of those in the imatinib group and 24 percent of those in the group given interferon plus cytarabine ( P=0.003 ) . On the basis of the rates of complete cytogenetic remission of 68 percent in the imatinib group and 7 percent in the group given interferon plus cytarabine at 12 months , an estimated 39 percent of all patients treated with imatinib but only 2 percent of all those given interferon plus cytarabine had a reduction in BCR-ABL transcript levels of at least 3 log ( P<0.001 ) . For patients who had a complete cytogenetic remission and a reduction in transcript levels of at least 3 log at 12 months , the probability of remaining progression-free was 100 percent at 24 months , as compared with 95 percent for such patients with a reduction of less than 3 log and 85 percent for patients who were not in complete cytogenetic remission at 12 months ( P<0.001 ) . CONCLUSIONS The proportion of patients with CML who had a reduction in BCR-ABL transcript levels of at least 3 log by 12 months of therapy was far greater with imatinib treatment than with treatment with interferon plus cytarabine . Patients in the imatinib group with this degree of molecular response had a negligible risk of disease progression during the subsequent 12 months BACKGROUND Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib . We evaluated the efficacy and safety of nilotinib , as compared with imatinib , in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia ( CML ) in the chronic phase . METHODS In this phase 3 , r and omized , open-label , multicenter study , we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib ( at a dose of either 300 mg or 400 mg twice daily ) or imatinib ( at a dose of 400 mg once daily ) . The primary end point was the rate of major molecular response at 12 months . RESULTS At 12 months , the rates of major molecular response for nilotinib ( 44 % for the 300-mg dose and 43 % for the 400-mg dose ) were nearly twice that for imatinib ( 22 % ) ( P<0.001 for both comparisons ) . The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib ( 80 % for the 300-mg dose and 78 % for the 400-mg dose ) than for imatinib ( 65 % ) ( P<0.001 for both comparisons ) . Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase 
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The results were robust to multiple sensitivity analyses .
When imatinib loses patent protection and its price declines , its use will be the cost-effective initial treatment strategy for CML-CP