***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 International Prognostic Index ( IPI ) is widely used for risk stratification of patients with aggressive B-cell lymphoma . The introduction of rituximab has markedly improved outcome , and R-CHOP ( rituximab + cyclophosphamide , doxorubicin , vincristine , prednisone ) has become the st and ard treatment for CD20(+ ) diffuse large B-cell lymphoma . To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP , we analyzed the prognostic relevance of IPI in three prospect i ve clinical trials . PATIENTS AND METHODS In total , 1,062 patients treated with rituximab were included ( MabThera International Trial [ MInT ] , 380 patients ; dose-escalated regimen of cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ( MegaCHOEP ) trial , 72 patients ; CHOP + rituximab for patients older than age 60 years [ RICOVER-60 ] trial , 610 patients ) . A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free , progression-free , and overall survival . RESULTS IPI score was significant for all three end points . Rituximab significantly improved treatment outcome within each IPI group result ing in a quenching of the Kaplan-Meier estimators . However , IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid . The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP . CONCLUSION The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy . These results demonstrate that the IPI is still valid in the R-CHOP era 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 18F-fluorodeoxyglucose positron emission tomography ( FDG-PET ) documented response after salvage chemotherapy has been reported to impact survival in patients with aggressive non-Hodgkin ’s lymphoma , especially diffuse large B cell lymphoma ( DLBCL ) undergoing high dose chemotherapy and autologous SCT ( HDC auto-SCT ) . We review ed the impact of 19 different prognostic/predictive factors before salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC auto-SCT outcome . The Fine and Gray method for competing risk analysis and a regression model was used to assess the risk associated with different factors on outcome . Fifty-five patients had FDG-PET after salvage chemotherapy ; male 65 % , female 45 % , relapsed 55 % , refractory 45 % , DLBCL 82 % , T cell lymphoma 18 % , median age at auto-SCT 40 years , median follow-up 42.4 months . Multivariate analysis identified only positive FDG-PET ( P=0.04 ) and mediastinal involvement ( P=0.05 ) with higher hazard rate of disease-specific death ( model P=0.008 ) but only positive FDG-PET ( P=0.01 ) for disease-specific events ( persistent , progressive or relapsed disease ) . Cumulative incidence of disease-specific death for patients with 0 , 1 and 2 risk factors was 5 , 30 and 62 % , respectively ( P=0.01 ) . Our model is significant and showed an increasing risk of failure with mediastinal involvement and post-salvage positive FDG-PET BACKGROUND High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin 's lymphoma who have relapses . In this report we describe a prospect i ve r and omized study of such treatment . METHOD A total of 215 patients with relapses of non-Hodgkin 's lymphoma were treated between July 1987 and June 1994 . All patients received two courses of conventional chemotherapy . The 109 patients who had a response to chemotherapy were r and omly assigned to receive four courses of chemotherapy plus radiotherapy ( 54 patients ) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation ( 55 patients ) . RESULTS The overall rate of response to conventional chemotherapy was 58 percent ; among patients with relapses after chemotherapy , the response rate was 64 percent , and among those with relapses during chemotherapy , the response rate was 21 percent . There were three deaths from toxic effects among the patients in the transplantation group , and none among those in the group receiving chemotherapy without transplantation . The two groups did not differ in terms of prognostic factors . The median follow-up time was 63 months . The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation . At five years , the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation ( P = 0.001 ) , and the rate of overall survival was 53 and 32 percent , respectively ( P = 0.038 ) . CONCLUSIONS As compared with conventional chemotherapy , treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin 's lymphoma in relapse Second-line chemotherapy followed by high-dose therapy ( HDT ) with autologous stem cell transplantation ( ASCT ) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ) . Prognostic models capable of predicting outcome are essential . In 3 sequential clinical trials , conducted from January 1993 to August 2000 , we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide , carboplatin , and etoposide ( ICE ) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease . We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy ( sAAIPI ) as a predictor of progression-free survival ( PFS ) and overall survival ( OS ) . At a median follow-up of 4 years , the PFS and OS are 28 % and 34 % by intention to treat and 39 % and 45 % for only those patients with chemosensitive disease . Three risk groups with different PFS and OS were identified by the sAAIPI : low risk ( 0 factors ) , 70 % and 74 % ; intermediate risk ( 1 factor ) , 39 % and 49 % ; and high risk ( 2 or 3 factors ) , 16 % and 18 % ( P < .001 for both PFS and OS ) . The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease : low risk , 69 % and 83 % ; intermediate risk , 46 % and 55 % ; and high risk , 25 % and 26 % ( P < .001 PFS and OS ) . The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive population s. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens Allogeneic SCT is an effective therapy for lymphoma .  Reduced-intensity conditioning ( RIC ) 
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At present , pretransplant FDG-PET can not be recommended in aggressive non-Hodgkin lymphoma , because available studies suffer from major method ological flaws , and reported prognostic estimates are low ( i.e. , poor in newly diagnosed and moderate in refractory/relapsed aggressive non-Hodgkin lymphoma )