***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: Blast crisis is the most advanced stage of chronic myelogenous leukemia ( CML ) and is highly refractory to therapy . CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Imatinib ( Glivec , formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl tyrosine kinase . A total of 260 patients with CML were enrolled in a phase II trial , of whom 229 had a confirmed diagnosis of CML in blast crisis . Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg . Imatinib induced hematologic responses in 52 % of patients and sustained hematologic responses lasting at least 4 weeks in 31 % of patients , including complete hematologic responses in 8 % . For patients with a sustained response , the estimated median response duration was 10 months . Imatinib induced major cytogenetic responses in 16 % of patients , with 7 % of the responses being complete . Median survival time was 6.9 months . Nonhematologic adverse reactions were frequent but generally mild or moderate . Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib . Drug-related adverse events led to discontinuation of therapy in 5 % of patients , most often because of cytopenia , skin disorders , or gastrointestinal reactions . These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis . Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia ( CML ) . Since tyrosine kinase activity is essential to the transforming function of BCR-ABL , an inhibitor of the kinase could be an effective treatment for CML . METHODS We conducted a phase 1 , dose-escalating trial of STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase . STI571 was administered orally to 83 patients with CML in the chronic phase in whom treatment with interferon alfa had failed . Patients were successively assigned to 1 of 14 doses ranging from 25 to 1000 mg per day . RESULTS Adverse effects of STI571 were minimal ; the most common were nausea , myalgias , edema , and diarrhea . A maximal tolerated dose was not identified . Complete hematologic responses were observed in 53 of 54 patients treated with daily doses of 300 mg or more and typically occurred in the first four weeks of therapy . Of the 54 patients treated with doses of 300 mg or more , cytogenetic responses occurred in 29 , including 17 ( 31 percent of the 54 patients who received this dose ) with major responses ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) ; 7 of these patients had complete cytogenetic remissions . CONCLUSIONS STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed . Our results provide evidence of the essential role of BCR-ABL tyrosine kinase activity in CML and demonstrate the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer BACKGROUND BCR-ABL , a constitutively activated tyrosine kinase , is the product of the Philadelphia chromosome . This enzyme is present in virtually all cases of chronic myeloid leukemia ( CML ) throughout the course of the disease , and in 20 percent of cases of acute lymphoblastic leukemia ( ALL ) . On the basis of the substantial activity of the inhibitor in patients in the chronic phase , we evaluated STI571 ( formerly known as CGP 57148B ) , a specific inhibitor of the BCR-ABL tyrosine kinase , in patients who had CML in blast crisis and in patients with ALL who had the Ph chromosome . METHODS In this dose-escalating pilot study , 58 patients were treated with STI571 ; 38 patients had a myeloid blast crisis and 20 had ALL or a lymphoid blast crisis . Treatment was given orally at daily doses ranging from 300 to 1000 mg . RESULTS Responses occurred in 21 of 38 patients ( 55 percent ) with a myeloid-blast-crisis phenotype ; 4 of these 21 patients had a complete hematologic response . Of 20 patients with a lymphoid blast crisis or ALL , 14 ( 70 percent ) had a response , including 4 who had complete responses . Seven patients with a myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment . All but one patient with a lymphoid blast crisis or ALL has relapsed . The most frequent adverse effects were nausea , vomiting , edema , thrombocytopenia , and neutropenia . CONCLUSIONS The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL Chronic myelogenous leukemia ( CML ) is caused by expression of the BCR-ABL tyrosine kinase oncogene , the product of the t(9;22 ) Philadelphia translocation . Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies . Imatinib ( formerly STI571 ) is a rationally developed , orally administered inhibitor of the Bcr-Abl kinase . A total of 235 CML patients were enrolled in this study , of whom 181 had a confirmed diagnosis of accelerated phase . Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response , time to progression , survival , and toxicity .  Imatinib induced hematologic response in 82 % of patients and sustained hematologic responses lasting at least 4 weeks in 69 % ( complete in 34 % ) . The rate of major cytogenetic response was 24 % ( complete in 17 % ) . Estimated 12-month progression-free and overall survival rates were 59 % and 74 % , respectively . Nonhematologic toxicity was usually mild or moderate , and hematologic toxicity was manageable . In comparison to 400 mg , imatinib doses of 600 mg/d led to more cytogenetic responses ( 28 % compared to 16 % ) , longer duration of response ( 79 % compared to 57 % at 12 months ) , time to disease progression ( 67 % compared to 44 % at 12 months ) , and overall survival ( 78 % compared to 65 % at 12 months ) , with no clinical ly relevant increase in toxicity . Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase . A daily dose of 600 mg is more effective than 400 mg , with similar toxicity BACKGROUND Treatment with interferon prolongs survival in chronic myelogenous leukemia . We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine . METHODS Previously untreated patients with chronic myelogenous leukemia were r and omly assigned to receive either hydroxyurea ( 50 mg per kilogram of body weight per day ) and interferon alfa-2b ( 5 million units per square meter of body-surface area per day ) , or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine ( 20 mg per square meter per day , for 10 days ) . The end points were overall survival , complete hematologic remission at 6 months , and major cytogenetic response ( less than 35 percent Philadelphia chromosome-positive cells in the bone marrow ) at 12 months . RESULTS The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine . A significant improvement in survival was observed in the  interferon-cytarabine group ( 360 patients ) as compared with the interferon group ( 361 patients ) ( P=0.02 ; relative risk of death , 0.64 ; 95 percent confidence interval , 0.44 to 0.93 ) . After three years , the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone . The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group ( P=0.003 ) . Major cytogenetic responses were observed 12 months after r and omization in 126 of 311 patients treated with interferon and cytarabine ( 41 percent ) and in 75 of 314 patients treated with interferon only ( 24 percent , P<0.001 ) . CONCLUSIONS The combination of interferon and cytarabine , as compared with interferon alone , increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia 
    Output:
    
A systematic review of case-series reports shows imatinib , when indirectly compared to conventional therapy , improves overall 12-month survival , but not surrogate outcomes , in individuals with Philadelphia chromosome-positive chronic myeloid leukemia ( Ph+ CML ) in myeloid-blast crisis , and accelerated phase .
Surrogate outcomes , but not overall survival , were improved in chronic phase disease .
Preliminary data from one r and omized controlled trial suggest imatinib has a greater impact on surrogate outcomes compared to the combination of interferonalpha and cytarabine in patients undergoing treatment for chronic phase Ph+CML , however , it is not yet known whether it prolongs or improves quality of life