***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 The Pediatric Oncology Group adopted a histology-based approach to non-Hodgkin 's lymphoma and treated patients with advanced large-cell lymphoma on a separate protocol ( doxorubicin , vincristine , prednisone , 6-mercaptopurin , and methotrexate ; APO regimen ) . In this study , we assessed the effects of an intense antimetabolite therapy alternating with APO on overall survival ( OS ) and event-free survival ( EFS ) and looked into biologic correlates . PATIENTS AND METHODS From December 1994 to April 2000 , we enrolled 180 eligible pediatric patients with stage III/IV large-cell lymphoma ( LCL ) ; 90 patients were r and omly assigned to the intermediate-dose methotrexate ( IDM ) and high-dose cytarabine ( HiDAC ) arm , 85 patients to the APO arm , and five patients directly to the APO arm by study design due to CNS involvement . Planned therapy duration was 12 months . RESULTS The 4-year EFS for all patients was 67.4 % ( SE , 4.2 % ) , and OS was 80.1 % ( SE , 3.6 % ) without any significant difference between the two arms . The 4-year EFS and OS were 71.8 % ( SE , 6.1 % ) and 88.1 % ( SE , 4.4 % ) , respectively , for patients with anaplastic large-cell lymphoma , and 63.8 % ( SE , 10.3 % ) and 70.3 % ( SE , 9.0 % ) , respectively , for patients with diffuse large B-cell lymphoma . Only 11 patients required radiation ( due to unresponsive bulky disease or CNS involvement ) . The IDM/HiDAC arm was associated with more toxicity . CONCLUSION The efficacy of incorporating IDM/HiDAC in the treatment plan of pediatric and adolescent patients with advanced-stage LCL was inconclusive as to its effect on EFS , regardless of the lymphoma phenotype . It can not be excluded that with a higher number of patients , one treatment could prove superior and future studies will build on these data BACKGROUND AND OBJECTIVES This multinational retrospective study compares the outcomes of patients with primary mediastinal large B-cell lymphoma ( PMLBCL ) with sclerosis after first-generation ( dose-intensive regimens ) , third-generation ( alternating regimens ) and high-dose chemotherapy strategies , frequently with adjuvant radiation therapy . DESIGN AND METHODS Between August 1981 and December 1999 , a total of 426 previously untreated patients with confirmed diagnosis were enrolled in 20 institutions to receive combination chemotherapy with either first generation ( CHOP or CHOP-like ) regimens , third generation ( MACOP-B , VACOP-B , ProMACE CytaBOM ) regimens or high-dose chemotherapy ( HDS/ABMT ) . RESULTS With chemotherapy , complete response ( CR ) rates were 49 % ( 50/105 ) , 51 % ( 142/277 ) and 53 % ( 23/44 ) with first generation , third generation and high-dose chemotherapy strategies , respectively ; partial response ( PR ) rates were 32 % , 36 % and 35 % , respectively . All patients who achieved CR and 124/142 ( 84 % ) with PR had radiation therapy on the mediastinum . The final CR rates became 61 % for CHOP/CHOP-like regimens , 79 % for MACOP-B and other regimens , and 75 % for HDS/ABMT . After median follow-ups from attaining CR of 48.5 months for CHOP/CHOP-like regimens , 51.7 months for MACOP-B type regimens and 32.4 months for HDS/ABMT , relapses occurred in 15/64 ( 23 % ) , 27/218 ( 12 % ) and 0/33 ( 0 % ) patients , respectively . Projected 10-year progression-free survival rates were 35 % , 67 % and 78 % , respectively ( p=0.0000 ) . Projected 10-year overall survival rates were 44 % , 71 % and 77 % , respectively ( p=0.0000 ) , after median follow-ups from diagnosis of 52.3 months , 54.9 months and 35.8 months , respectively . INTERPRETATION AND CONCLUSIONS In patients with PMLBCL with sclerosis , MACOP-B plus radiation therapy may be a better strategy than other treatments ; these retrospective data need to be confirmed by prospect i ve studies . The encouraging survival results after high dose chemotherapy require confirmation in selected high-risk patients BACKGROUND Cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) is used to treat patients with non-Hodgkin lymphoma . Interval decrease from 3 weeks of treatment ( CHOP-21 ) to 2 weeks ( CHOP-14 ) , and addition of rituximab to CHOP-21 ( R-CHOP-21 ) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . This r and omised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14 . METHODS 1222 elderly patients ( aged 61 - 80 years ) were r and omly assigned to six or eight cycles of CHOP-14 with or without rituximab . Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement . The primary endpoint was event-free survival ; secondary endpoints were response , progression during treatment , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat . The trial is registered on National Cancer Institute website , number NCT00052936 and as EU-20243 . FINDINGS 3-year event-free survival was 47.2 % after six cycles of CHOP-14 ( 95 % CI 41.2 - 53.3 ) , 53.0 % ( 47.0 - 59.1 ) after eight cycles of CHOP-14 , 66.5 % ( 60.9 - 72.0 ) after six cycles of R-CHOP-14 , and 63.1 % ( 57.4 - 68.8 ) after eight cycles of R-CHOP-14 . Compared with six cycles of CHOP-14 , the improvement in 3-year event-free survival was 5.8 % ( -2.8 - 14.4 ) for eight cycles of CHOP-14 , 19.3 % ( 11.1 - 27.5 ) for six cycles of R-CHOP-14 , and 15.9 % ( 7.6 - 24.2 ) for eight cycles of R-CHOP-14 . 3-year overall survival was 67.7 % ( 62.0 - 73.5 ) for six cycles of CHOP-14 , 66.0 % ( 60.1 - 71.9 ) for eight cycles of CHOP-14 , 78.1 % ( 73.2 - 83.0 ) for six cycles of R-CHOP-14 , and 72.5 % ( 67.1 - 77.9 ) for eight cycles of R-CHOP-14 . Compared with treatment with six cycles of CHOP-14 , overall survival improved by -1.7 % ( -10.0 - 6.6 ) after eight cycles of CHOP-14 , 10.4 % ( 2.8 - 18.0 ) after six cycles of R-CHOP-14 , and 4.8 % ( -3.1 - 12.7 ) after eight cycles of R-CHOP-14 . In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference , and adjusting for known prognostic factors , all three intensified regimens improved 3-year event-free survival ( eight cycles of CHOP-14 : RR [ relative risk ] 0.76 [ 0.60 - 0.95 ] , p=0.0172 ; six cycles of R-CHOP-14 : RR 0.51 [ 0.40 - 0.65 ] , p<0.0001 ; eight cycles of R-CHOP-14 : RR 0.54 [ 0.43 - 0.69 ] , p<0.0001 ) . Progression-free survival improved after six cycles of R-CHOP-14 ( RR 0.50 [ 0.38 - 0.67 ] , p<0.0001 ) , and eight cycles of R-CHOP-14 ( RR 0.59 [ 0.45 - 0.77 ] , p=0.0001 ) . Overall survival improved only after six cycles of R-CHOP-14 ( RR 0.63 [ 0.46 - 0.85 ] , p=0.0031 ) . In patients with a partial response after four cycles of chemotherapy , eight cycles were not better than six cycles . INTERPRETATION Six cycles of R-CHOP-14 significantly improved event-free , progression-free , and overall survival over six cycles of CHOP-14 treatment . Response-adapted addition of chemotherapy beyond six cycles , though widely practice d , is not justified . Of the four regimens assessed in this study , six cycles of R-CHOP-14 is the preferred treatment for elderly patients , with which other approaches should be compared BACKGROUND The role of rituximab in combination with different CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined . We aim ed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients . METHODS 824 patients who were from 18 countries ; aged 18 - 60 years ; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index ( IPI ) , stage II-IV disease , or stage I disease with bulk were enrolled . These patients were r and omly assigned to six cycles of CHOP-like chemotherapy and rituximab ( n=413 ) or to six cycles of CHOP-like chemotherapy alone ( n=411 ) . Bulky and extranodal sites received additional radiotherapy . The primary endpoint was event-free survival ; secondary endpoints were response , progression under therapy , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat and per protocol . This trial is registered at http://www . clinical trials.gov , NCT 00064116 . FINDINGS After a median follow-up of 34 months ( range 0.03 - 61 ) , patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone ( 79 % [ 95 % CI 75 - 83 ] vs 59 % [ 54 - 64 ] ; difference between groups 20 % [ 13 - 27 ] , log-rank p<0.0001 ) , and had increased 3-year overall survival ( 93 % [ 90 - 95 ] vs 84 % [ 80 - 88 ] ; difference between groups 9 % [ 3 - 13 ] , log-rank p=0.0001 ) . Event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI : after chemotherapy and rituximab , a favourable subgroup ( ie , IPI=0 , no bulk ) could be defined from a less-favourable subgroup ( ie , IPI=1 or bulk , or both ) . Groups did not differ in the frequency of adverse events . INTERPRETATION Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients Background A phase II trial of dose-adjusted etoposide , prednisone , vincristine , cyclophosphamide , doxorubicin and rituximab ( DA-EPOCH-R ) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma . The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting . Design and Methods The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II .  Radiaton therapy was not permitted on study . Median age was 58 years ( range 23–83 ) and 40 % had high-intermediate or high International Prognostic Index risk . Immunohistochemical biomarkers for cell of origin and proliferation were performed . Results With a median follow up of 62 months , time to progression and overall survival were 81 % and 84 % , respectively , and time to progression was 87 % , 92 % and 54 % for low/low-intermediate , high-intermediate and high International Prognostic Index risk groups , respectively , at 5-years and beyond . The time to progression and event-free survival of germinal center B- 
    Output:
    
Data are insufficient to recommend a pediatric or an adult approach for AYAs with diffuse large B-cell lymphoma and anaplastic large cell lymphoma .
Dose-adjusted EPOCH-R seems to be a promising , radiation-free approach for AYAs with primary mediastinal B-cell lymphoma .