***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 benefit of high-dose chemotherapy with autologous stem-cell transplantation ( ASCT ) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate . To address this point , we design ed a r and omized phase III trial to compare rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone (R-CHOP)-14 ( eight cycles ) with rituximab plus high-dose sequential chemotherapy ( R-HDS ) with ASCT . Patients and Methods From June 2005 to June 2011 , 246 high-risk patients with a high-intermediate ( 56 % ) or high ( 44 % ) International Prognostic Index score were r and omly assigned to the R-CHOP or R-HDS arm , and 235 were analyzed by intent to treat . The primary efficacy end point of the study was 3-year event-free survival , and results were analyzed on an intent-to-treat basis . Results Clinical response ( complete response , 78 % v 76 % ; partial response , 5 % v 9 % ) and failures ( no response , 15 % v 11 % ; and early treatment-related mortality , 2 % v 3 % ) were similar after R-CHOP versus R-HDS , respectively . After a median follow-up of 5 years , the 3-year event-free survival was 62 % versus 65 % ( P = .83 ) . At 3 years , compared with the R-CHOP arm , the R-HDS arm had better disease-free survival ( 79 % v 91 % , respectively ; P = .034 ) , but this subsequently vanished because of late-occurring treatment-related deaths . No difference was detected in terms of progression-free survival ( 65 % v 75 % , respectively ; P = .12 ) , or overall survival ( 74 % v 77 % , respectively ; P = .64 ) . Significantly higher hematologic toxicity ( P < .001 ) and more infectious complications ( P < .001 ) were observed in the R-HDS arm . Conclusion In this study , front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas BACKGROUND High-dose therapy ( HDT ) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma . We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation ( ASCT ) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities . METHODS We did an open-label , r and omised trial comparing conventional chemotherapy ( cyclophosphamide , doxorubicin , vincristine , etoposide , prednisone ) and rituximab ( R-CHOEP-14 ) with dose-escalated sequential HDT and rituximab ( R-MegaCHOEP ) followed by repetitive ASCT in high-risk ( age-adjusted International Prognostic Index [ IPI ] 2 or 3 ) patients aged 18 - 60 years with aggressive B-cell lymphoma . Eligible patients received radiotherapy for bulky , extranodal disease , or both . R and omisation ( 1:1 ) used the Pocock minimisation algorithm ; patients were stratified by age-adjusted IPI factors , bulky disease , and centre . The primary endpoint was event-free survival . All analyses were done on the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00129090 . FINDINGS 136 patients were r and omly assigned to  R-CHOEP-14  and 139 to R-MegaCHOEP  . 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population . After a median of 42 months ( IQR 29 - 59 ) , 3-year event-free survival was 69·5 % ( 95 % CI 61·3 - 77·7 ) in the R-CHOEP-14 group and 61·4 % ( 52·8 - 70·0 ) in the R-MegaCHOEP group ( p=0·14 ; hazard ratio 1·3 , 95 % CI 0·9 - 2·0 ) . All 128 evaluable patients treated with R-MegaCHOEP  had grade 4 leucopenia , as did 48 ( 58·5 % ) of 82 patients with documented blood counts in the R-CHOEP-14 group . All 128 evaluable patients in the R-MegaCHOEP group had grade 3 - 4 thrombocytopenia , as did 26 ( 33·8 % ) of 77 patients in the R-CHOEP-14 group with documented blood counts . The most important non-haematological grade 3 or 4 adverse event was infection , which occurred in 96 ( 75·0 % ) of 128 patients treated with R-MegaCHOEP and in 40 ( 31·3 % ) of 128 patients treated with R-CHOEP-14 . INTERPRETATION In young patients with high-risk aggressive B-cell lymphoma  , R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects . R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients , with encouraging efficacy . FUNDING Deutsche Krebshilfe PURPOSE Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) is the st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) . Salvage regimens have never been compared ; their efficacy in the rituximab era is unknown . PATIENTS AND METHODS Patients with CD20(+ ) DLBCL in first relapse or who were refractory after first-line therapy were r and omly assigned to either rituximab , ifosfamide , etoposide , and carboplatin ( R-ICE ) or rituximab , dexamethasone , high-dose cytarabine , and cisplatin ( R-DHAP ) . Responding patients received high-dose chemotherapy and ASCT . RESULTS The median age of the 396 patients enrolled ( R-ICE , n = 202 ; R-DHAP , n = 194 ) was 55 years . Similar response rates were observed after three cycles of R-ICE ( 63.5 % ; 95 % CI , 56 % to 70 % ) and R-DHAP ( 62.8 % ; 95 CI , 55 % to 69 % ) . Factors affecting response rates ( P < .001 ) were refractory disease/relapse less than versus more than 12 months after diagnosis ( 46 % v 88 % , respectively ) , International Prognostic Index ( IPI ) of more than 1 versus 0 to 1 ( 52 % v 71 % , respectively ) , and prior rituximab treatment versus no prior rituximab ( 51 % v 83 % , respectively ) . There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival ( EFS ) or overall survival . Three-year EFS was affected by prior rituximab treatment versus no rituximab ( 21 % v 47 % , respectively ) , relapse less than versus more than 12 months after diagnosis ( 20 % v 45 % , respectively ) , and IPI of 2 to 3 versus 0 to 1 ( 18 % v 40 % , respectively ) . In the Cox model , these parameters were significant ( P < .001 ) . CONCLUSION In patients who experience relapse more than 12 months after diagnosis , prior rituximab treatment does not affect EFS . Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis , with no difference between the effects of R-ICE and R-DHAP Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p < 0.001 ) in the review ers ’ assessment ( median = 6 ; interquartile range [ IQR ] 6–6 ) compared with those by authors ( median = 5 , IQR 4–6 ) . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review BACKGROUND The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown . METHODS We compared high-dose therapy plus autologous stem-cell support with the st and ard regimen of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) in a r and omized trial . The patients were 15 to 60 years of age , had untreated aggressive lymphoma , and were at low , low intermediate , or high intermediate risk of death ( i.e. , a maximum of two adverse prognostic factors ) according to the age-adjusted International Prognostic Index . The primary outcome was event-free survival at five years . RESULTS Of 207 consecutive patients , 197 underwent r and omization ; 99 were assigned to receive CHOP , and 98 to receive high-dose chemotherapy plus stem-cell transplantation .  Overall , 78 percent of the patients completed the assigned treatment ; the median follow-up was four years . The estimated event-free survival rate ( + /-SD ) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP ( 55+/-5 percent vs. 37+/-5 percent , P=0.037 ) . Among patients with a high intermediate risk of death , according to the age-adjusted International Prognostic Index , the five-year survival rate was significantly higher after high-dose therapy than after CHOP ( 74+/-6 percent vs. 44+/-7 percent , P=0.001 ) . CONCLUSIONS High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab .  After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - 
    Output:
    
High-intermediate or high-risk untreated patients with DLBCL only achieved short-term survival benefit with the upfront ASCT