***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: Approximately 5 % to 10 % of diffuse large B-cell lymphomas ( DLBCLs ) harbor an MYC oncogene rearrangement ( MYC+ ) . The prognostic significance of MYC+ DLBCL was determined in an unselected population of patients with newly diagnosed DLBCL treated with rituximab in combination with cyclophosphamide , doxorubicin , vincristine , and prednisone chemotherapy ( R-CHOP ) .  Using a Vysis break-apart fluorescence in situ hybridization probe , 12 of 135 ( 8.8 % ) cases of MYC+ DLBCL were identified that had no defining high-risk features . MYC+ DLBCL was associated with an inferior 5-year progression-free survival ( 66 % vs 31 % , P = .006 ) and overall survival ( 72 % vs 33 % , P = .016 ) . Multivariate analysis confirmed the prognostic importance of MYC for both progression-free survival ( hazard ratio = 3.28 ; 95 % confidence interval , 1.49 - 7.21 , P = .003 ) and overall survival ( hazard ratio = 2.98 ; 95 % confidence interval , 1.28 - 6.95 , P = .011 ) . Cases of MYC+ DLBCL also had a higher risk of central nervous system relapse ( P = .023 ) , independent of other risk factors . The diagnosis of MYC+ DLBCL is likely underappreciated ; and given the lack of defining risk factors , fluorescence in situ hybridization for MYC rearrangements should be performed in all patients with DLBCL . In the R-CHOP treatment era , MYC+ DLBCLs have an inferior prognosis . Treatment regimens similar to those used in Burkitt lymphoma may be more appropriate in this patient population and need to be prospect ively tested BACKGROUND The st and ard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) . Rituximab , a chimeric monoclonal antibody against the CD20 B-cell antigen , has therapeutic activity in diffuse large-B-cell lymphoma . We conducted a r and omized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma . METHODS Previously untreated patients with diffuse large-B-cell lymphoma , 60 to 80 years old , were r and omly assigned to receive either eight cycles of CHOP every three weeks ( 197 patients ) or eight cycles of CHOP plus rituximab given on day 1 of each cycle ( 202 patients ) . RESULTS The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone ( 76 percent vs. 63 percent , P=0.005 ) . With a median follow-up of two years , event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group ( P<0.001 and P=0.007 , respectively ) . The addition of rituximab to st and ard CHOP chemotherapy significantly reduced the risk of treatment failure and death ( risk ratios , 0.58 [ 95 percent confidence interval , 0.44 to 0.77 ] and 0.64 [ 0.45 to 0.89 ] , respectively ) . Clinical ly relevant toxicity was not significantly greater with CHOP plus rituximab . CONCLUSIONS The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma , without a clinical ly significant increase in toxicity Recent retrospective studies of heterogeneously treated patients have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma ( DLBCL ) . Here , we investigated the prognostic impact of MYC aberrations analyzed by interphase fluorescence in situ hybridization in 177 patients with de novo DLBCL treated within the two prospect i ve , r and omized trials non-Hodgkin 's lymphoma NHL-B1 and NHL-B2 .  MYC aberrations were detected in 14 DLBCL ( 7.9 % ) . In a univariate analysis compared with MYC-negative DLBCL , MYC-positive cases showed a significantly shorter overall survival ( OS ) ( P=0.047 ) and relevantly , though not significantly , shorter event-free survival ( EFS ) ( P=0.062 ) . In a Cox model adjusted for the international prognostic index , the presence of a MYC gene rearrangement was the strongest statistically independent predictor of OS ( relative risk 3.4 , P=0.004 ) and EFS ( relative risk 2.5 , P=0.015 ) , and this also held true when the cell-of-origin signature detected by immunohistochemistry was included in the model BACKGROUND Although many patients with intermediate- grade or high- grade ( aggressive ) non-Hodgkin 's lymphoma are cured by combination chemotherapy , the remainder are not cured and ultimately die of their disease . The Ann Arbor classification , used to determine the stage of this disease , does not consistently distinguish between patients with different long-term prognoses . This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin 's lymphoma on the basis of the patients ' clinical characteristics before treatment . METHODS Adults with aggressive non-Hodgkin 's lymphoma from 16 institutions and cooperative groups in the United States , Europe , and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin  were evaluated for clinical features predictive of overall survival and relapse-free survival . Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death . RESULTS In 2031 patients of all ages , our model , based on age , tumor stage , serum lactate dehydrogenase concentration , performance status , and number of extranodal disease sites , identified four risk groups with predicted five-year survival rates of 73 percent , 51 percent , 43 percent , and 26 percent . In 1274 patients 60 or younger , an age-adjusted model based on tumor stage , lactate dehydrogenase level , and performance status identified four risk groups with predicted five-year survival rates of 83 percent , 69 percent , 46 percent , and 32 percent . In both models , the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response . These two indexes , called the international index and the age-adjusted international index , were significantly more accurate than the Ann Arbor classification in predicting long-term survival . CONCLUSIONS The international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin 's lymphoma and in the selection of appropriate therapeutic approaches for individual patients MYC rearrangements occur in 5 % to 10 % of diffuse large B-cell lymphomas ( DLBCL ) and confer an increased risk to cyclophosphamide , hydroxydaunorubicin , oncovin , and prednisone ( CHOP ) and rituximab (R)-CHOP treated patients . We investigated the prognostic relevance of MYC- , BCL2- and BCL6-rearrangements and protein expression in a prospect i ve r and omized trial . Paraffin-embedded tumor sample s from 442 de novo DLBCL treated within the RICOVER study of the German High- Grade Non-Hodgkin Lymphoma Study Group ( DSHNHL ) were investigated using immunohistochemistry and fluorescence in situ hybridization ( FISH ) to detect protein expression and breaks of MYC , BCL2 , and BCL6 . Rearrangements of MYC , BCL2 , and BCL6 were detected in 8.8 % , 13.5 % , and 28.7 % , respectively . Protein overexpression of MYC ( > 40 % ) was encountered in 31.8 % of tumors ; 79.6 % and 82.8 % of tumors expressed BCL2 and BCL6 , respectively . MYC translocations , MYChigh , BCL2high , and BCL6low protein expressions were associated with inferior survival . In multivariate Cox regression modeling , protein expression patterns of MYC , BCL2 and BCL6 , and MYC rearrangements were predictive of outcome and provided prognostic information independent of the International Prognostic Index ( IPI ) for overall survival and event-free survival . A combined immunohistochemical or FISH/immunohistochemical score predicts outcome in DLBCL patients independent of the IPI and identifies a subset of 15 % of patients with dismal prognosis in the high-risk IPI group following treatment with R-CHOP . Registered at http://www.cancer.gov/ clinical trials : RICOVER trial of the DSHNHL is NCT 00052936 Approximately 5 - 10 % of diffuse large B-cell lymphomas ( DLBCL ) harbor a 8q24/MYC rearrangement ( MYC(+ ) ) . We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospect ively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation .  Twenty-eight ( 17 % ) of the 161 patients analyzed presented a MYC(+ ) rearrangement , targeted as either simple hit ( 25 % ) or complex hits ( n=75 % ) including MYC/BCL2 , MYC/BCL6 , and MYC/BCL2/BCL6 . Results were statistically highly concordant in matched primary and relapsed biopsies ( n = 45 ) . Compared to the MYC(- ) DLBCL patients , the MYC(+ ) DLBCL patients presented with a more elevated lactico-deshydrogenase level ( P = .0006 ) and a more advanced age adjusted international prognostic index ( P = .0039 ) . The 4-year PFS and OS were significantly lower in the MYC(+ ) DLBCL patients than those in the MYC(- ) DLBCL patients , with rates of 18 % vs 42 % ( P = .0322 ) , and of 29 % vs 62 % ( P = .0113 ) , respectively . Type of treatment , R-DHAP or R-ICE , had no impact on survivals , with 4-year PFS rates of 17 % vs 19 % and 4-year OS rates of 26 % vs 31 % . In conclusion , MYC rearrangement is an early event in DLBCL . MYC(+ ) DLBCL patients have a significant inferior prognosis than MYC(- ) DLBCL patients . Their outcome was not influenced by the proposed salvage therapy 
    Output:
    
C-MYC aberrations appeared to play an independent role among other well-known prognostic factors in DLBCL .
Addition of rituximab could not overcome the inferior prognosis conferred by C-MYC .
The present systematic review and meta- analysis confirm the prognostic value of C-MYC aberrations .
Screening of C-MYC should have definite prognostic meaning for DLBCL stratification , thus guaranteeing a more tailored therapy