***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: Fifty-six untreated patients with childhood with acute lymphoblastic leukemia ( ALL ) were r and omized to receive one of three remission induction regimens : vincristine and prednisone ( VP ) , vincristine , prednisone and daunorubicin ( VPD ) , or vincristine , prednisone and adriamycin ( VPA ) . The complete remission rate was similar for all three groups . Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group , this difference was not significant . Labeling index reduction between study days 1 and 5 was significantly greater ( p less than 0.001 ) with an anthracycline than for the VP group , but there was no difference between the two anthracyclines . Granulocytopenia during induction was significantly increased ( p less than 0.05 ) in both the VPD and VPA groups as compared with VP alone . A significantly higher rate of infectious morbidity ( p less than 0.01 ) was associated with the addition of either anthracycline , but to date no significant differences in remission duration or survival have been observed . The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages , but may be undesirable because of increased morbidity Two groups of children with acute lymphoblastic leukemia or non-Hodgkin lymphoma , treated with anthracyclines ( ANT ) , were studied : group I , consisting of 10 patients , with coenzyme Q10 ( CoQ ) therapy ;  group II , consisting of 10 patients without CoQ therapy . The ANT cumulative dose was 240 + /- 20.0 mg/m2 in group I and 252.0 + /- 20.1 mg/m2 in group II . Echocardiographic study was performed at the beginning , at the cumulative dose of 180 mg/m2 and at the end of therapy with ANT .  Percentage left ventricular fractional shortening ( % LVFS ) decreased from baseline ( 40.36 + /- 4.6 ) to end value ( 35.82 + /- 5.02 ) ( P < 0.05 ) in group I ; % LVFS decreased from baseline ( 39.89 + /- 4.37 ) to end value ( 33.43 + /- 3.46 ) ( P < 0.002 ) in group II . Interventricular septum wall thickening decreased only in group II from baseline ( 46.10 + /- 10.1 ) to end therapy ( 27.00 + /- 18.54 ) ( P < 0.01 ) . Septum wall motion abnormalities were detected only in 2 patients of group II . These data demonstrate a protective effect of CoQ on cardiac function during therapy with ANT The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks .  Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy BACKGROUND Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia ( ALL ) but also injures myocardial cells . Dexrazoxane , a free-radical scavenger , may protect the heart from doxorubicin-associated damage . METHODS To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes , we r and omly assigned 101 children with ALL to receive doxorubicin alone  ( 30 mg per square meter of body-surface area every three weeks for 10 doses ) and 105 to receive dexrazoxane ( 300 mg per square meter ) followed immediately by doxorubicin . Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin . A total of 2377 serum sample s ( mean , 15.1 sample s per patient ) were obtained before , during , and after treatment with doxorubicin .  Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( > 0.01 ng per milliliter)--the primary end point -- or extremely elevated ( > 0.025 ng per milliliter ) . RESULTS Elevations of troponin T occurred in 35 percent of the patients ( 55 of 158 ) . Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels ( 50 percent vs. 21 percent , P<0.001 ) and extremely elevated troponin T levels ( 32 percent vs. 10 percent , P<0.001 ) . The median follow-up was 2.7 years . The rate of event-free survival at 2.5 years was 83 percent in both groups ( P=0.87 by the log-rank test ) . CONCLUSIONS Dexrazoxane prevents or reduces cardiac injury , as reflected by elevations in troponin T , that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin . Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival Summary During the 1970s , despite apparently similar treatment , the prognosis for children with lymphoblastic leukaemia ( ALL )  improved more in some countries , notably the United States and West Germany , than in others . To find out why , the first phase of the United Kingdom ( UK ) Medical Research Council ( MRC ) childhood ALL trial , UKALL VIII , was design ed to see whether similar results to the United States Children 's Cancer Study Group ( CCSG ) could be obtained in the U.K. using an identical protocol ( CCG 162 ) . Protocol 162 was one of a series of regimens devised by the American Children 's Cancer Study Group in the 1970s and was used specifically for their average risk patients ( all children with ALL with an initial white cell count up to 50 × 109/l except those aged 3–6 years with white cell counts under 10 × 109/l ) . One arm ( 1A ) of their study was adopted by the MRC for all children in the U.K. aged 0–14 years with confirmed ALL PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug , but mechanisms of cardiotoxicity are different in children . We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin .  PATIENTS AND METHODS In a r and omized study , children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2 ) in 30-mg/m(2 ) doses every 3 weeks either by bolus ( within 1 hour , n = 57 ) or by continuous infusion ( over 48 hours , n = 64 ) . Echocardiograms obtained before doxorubicin and at longest follow-up times were central ly remeasured , and z scores of cardiac measurements were calculated based on a healthy population . RESULTS The groups were similar in age , sex distribution , doxorubicin dose , and duration of follow-up . Before treatment , measures of left ventricular ( LV ) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups . The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic , but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline . For example , the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms . LV contractility was depressed in both groups ( for bolus patients , median z score = -0.70 SD , P = .006 ; for continuous-infusion patients , median z score = -0.765 , P = .005 ) . Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups . Clinical cardiac manifestations and event-free survival did not differ . CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion . Both regimens were associated with progressive sub clinical cardiotoxicity . Other cardioprotective strategies should be explored BACKGROUND Daunorubicin ( DNR ) is one of the most important drugs in treatment of acute lymphoblastic leukemia ( ALL ) . Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions . PROCEDURE In the cooperative treatment study COALL-92 for childhood ALL 178 patients were r and omized to receive in a therapeutic window a single dose of 36 mg/m ( 2 ) DNR either as a 1-h  ( 85 patients ) or 24-h infusion ( 93 patients ) . Daily measurements of white blood cell count ( WBC ) and peripheral blood smears for seven days could be evaluated central ly in 101 patients ( 1-h : 43 patients , 24-h : 58 patients ) . RESULTS The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms . At day 3 the median percentage of blasts was less than 10 % , at day 7 less than 2 % for either the 1-h or 24-h infusion . Twelve patients ( 1-h : 5 patients , 24-h : 7 patients ) had an absolute number of more than 1000 blasts per mul peripheral blood ( PB ) at day 7 after DNR infusion ( DNR poor responders ) . Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group ( 24-h : 83%+/-5 ; 1-h : 81+/-6 ) after a median observation time of 12.3 years . CONCLUSIONS We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion . This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy Background . Improved survival of children with acute lymphoblastic leukemia ( ALL ) has made it more difficult to develop new protocol s to further improve results . The authors report the pilot experience with the Memorial Sloan‐Kettering‐New York‐II ( MSK‐NY‐II ) protocol , based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity PURPOSE Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity . A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms ( SMNs ) in children with Hodgkin 's disease . We report the absence of an association of SMNs in children with acute lymphoblastic leukemia ( ALL ) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95 - 01 . PATIENTS AND METHODS Two hundred five children with high-risk ( HR ) ALL were r and omly assigned to receive doxorubicin alone ( n = 100 ) or doxorubicin with dexrazoxane ( n = 105 ) during the induction and intensification phases of multiagent chemotherapy . We compared incidence of SMNs in these two groups . RESULTS With a median follow-up of 6.2 years , no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the 
    Output:
    
Data from 958 patients in 4 trials , recruiting between 1972 and 1984 , showed that addition of an anthracycline reduced bone marrow relapse and , non-significantly , non-bone marrow relapse , result ing in an increased relapse-free interval .
The limited data from trials did not demonstrate differences in clinical ly evident cardiotoxicity .
Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL .