***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 
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    Input: BACKGROUND Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin 's lymphoma . In 1986 , we design ed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin 's lymphoma . METHODS The trial involved 242 patients with advanced low- grade follicular non-Hodgkin 's lymphoma selected on the basis of clinical , radiographic , and biologic criteria . All patients were treated with a regimen consisting of cyclophosphamide , doxorubicin , teniposide , and prednisone ( CHVP ) , given monthly for six cycles and then every two months for one year . After r and omization , 123 patients also received interferon alfa-2b  at a dosage of 5 million units three times weekly for 18 months . The remaining 119 patients received chemotherapy alone . RESULTS As compared with the patients treated with CHVP only , the patients treated with CHVP plus interferon alfa had a higher overall rate of response ( 85 percent vs. 69 percent , P = 0.006 ) , a longer median event-free survival ( 34 months vs. 19 months , P < 0.001 ) , and a higher rate of survival at 3 years ( 86 percent vs. 69 percent , P = 0.02 ) . Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone . There were no treatment-related deaths . Interferon alfa had to be stopped because of toxic effects ( fatigue and hepatitis ) in 13 patients ( 11 percent ) . CONCLUSIONS The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response , event-free survival , and overall survival in patients with advanced follicular non-Hodgkin 's lymphoma , without serious toxicity , although some patients were unable to tolerate the side effects A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were r and omly assigned treatment with cyclophosphamide , vincristine , and prednisone plus BCNU ( BCOP ) or doxorubicin ( CHOP ) . In diffuse histiocytic ( DH ) lymphoma , CHOP produced superior complete ( 54 % v 34 % ) and total ( 70 % v 46 % ) response rates . Among the responders to either therapy , no differences were seen in duration of response or survival times . Median duration of response has not been reached with follow-up in excess of 50 months . In categories of lymphoma other than DH ( including small-cell , mixed , and nodular histiocytic lymphomas ) , complete ( 27 % v 29 % ) and total ( 48 % v 54 % ) responses were similar for BCOP and CHOP , as were duration s of response and survival . These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas . CHOP appears preferable for diffuse large-cell categories , since it result ed in greater overall survival in patients with DH lymphoma ; this was due to a significantly greater response rate , since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders PURPOSE The aim of the F2 study was to verify whether a prospect i ve collection of data would enable the development of a more accurate prognostic index for follicular lymphoma ( FL ) by using parameters which could not be retrospectively studied before , and by choosing progression-free survival ( PFS ) as principal end point . PATIENTS AND METHODS Between January 2003 and May 2005 , 1,093 patients with a newly diagnosed FL were registered and 942 individuals receiving antilymphoma therapy were selected as the study population . The variables we used for score definition were selected by means of bootstrap resampling procedures on 832 patients with complete data . Procedures to select the model that would minimize errors were also performed . RESULTS After a median follow-up of 38 months , 261 events for PFS evaluation were recorded . beta2-microglobulin higher than the upper limit of normal , longest diameter of the largest involved node longer than 6 cm , bone marrow involvement , hemoglobin level lower than 12 g/dL , and age older than 60 years were factors independently predictive for PFS . Using these variables , a prognostic model was devised to identify three groups at different levels of risk . The 3-year PFS rate was 91 % , 69 % , and 51 % for patients at low , intermediate , and high risk , respectively ( log-rank = 64.6 ; P < .00001 ) . The 3-year survival rate was 99 % , 96 % , and 84 % for patients at low , intermediate , and high risk , respectively ( P < .0001 ) . CONCLUSION Follicular Lymphoma International Prognostic Index 2 is a simple prognostic index based on easily available clinical data and may represent a promising new tool for the identification of patients with FL at different risk in the era of immunochemotherapy Between July 1 , 1971 and December 31 , 1978 , 150 patients with favorable subtypes of non-Hodgkin 's lymphoma [ nodular poorly differentiated lymphocytic ( NLPD ) , nodular mixed , or diffuse well differentiated lymphocytic ] were entered into prospect i ve r and omized clinical trials at Stanford University . Treatments included involved field , total lymphoid , or whole body irradiation , single alkylating agent chemotherapy , combination chemotherapy with cyclophosphamide , vincristine and prednisone ( CVP ) or with cyclophosphamide , vincristine , procarbazine , and prednisone ( C-MOPP ) , or various combinations of chemotherapy and irradiation . The initial complete response rate ( CR ) was 79 % . Among patients who achieved a CR , 31 % later relapsed . There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed . Histologic conversion ( change from initially favorable to an unfavorable subtype of non-Hodgkin 's lymphoma ) was documented in 22/78 patients ( 28 % ) . However , the actuarial risk for conversion was actually much greater ( 60 % at 8 yr ) . The median time to documentation of conversion was 51 mo . The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma . Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma , and the median survival after conversion was less than 1 yr . However , those patients who achieved a CR after conversion had a more favorable outcome ( actuarial survival 75 % at 5 yr ) . No specific risk factors predictive of histologic conversion could be identified One hundred patients with untreated non-Hodgkin 's lymphoma were entered in a prospect i ve r and omized study in South and West Wales design ed to assess the value of the anthracycline antibiotic , epirubicin ( 4'-epidoxorubicin ) , in their management . Patients with low grade histology and progressive disease were r and omized to receive either epirubicin , vincristine and prednisolone ( EVP ) or cyclophosphamide , vincristine and prednisolone ( CVP ) . The response rate of 81 % in patients receiving EVP with complete remission rate of 52 % were similar to a response rate of 88 % and complete remission rate of 58 % for patients receiving CVP . No difference was observed in survival between the two groups . Patients with high grade lymphoma were r and omized to receive either cyclophosphamide , doxorubicin , vincristine and prednisolone ( CHOP ) or cyclophosphamide , epirubicin , vincristine and prednisolone ( CEOP ) . The response rate was 71 % for CHOP and 84 % for CEOP . The complete remission rates were 46 % for CHOP and 61 % for CEOP . The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals . Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin . Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin PURPOSE Advanced-stage follicular lymphoma is considered incurable . The pace of improvements in treatment has been slow . This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002 . METHODS Five consecutive studies ( two were r and omized trials ) involving 580 patients were analyzed for overall survival ( OS ) , failure-free survival ( FFS ) , and survival after first relapse . A proportional hazards analysis , and subset analyses using the follicular lymphoma international prognostic index ( FLIPI ) score were performed . Treatment regimens included : cyclophosphamide , doxorubicin , vincristine , prednisone , bleomycin ( CHOP-Bleo ) ; CHOP-Bleo followed by interferon alfa ( IFN-alpha ) ; a rotation of three regimens ( alternating triple therapy ) , followed by IFN-alpha ; fludarabine , mitoxantrone , dexamethasone ( FND ) followed by IFN-alpha ; and FND plus delayed versus concurrent rituximab followed by IFN-alpha . RESULTS Improvements in 5-year OS ( from 64 % to 95 % ) and FFS ( from 29 % to 60 % ) indicate steady progress , perhaps partly due to more effective salvage therapies , but the FFS data also indicate improved front-line therapies ; these observations held true after controlling for differences in prognostic factors among the cohorts . The FLIPI model adds rigor to and facilitates comparisons among the different cohorts . An unexpected finding in this study was a trend toward an apparent FFS plateau . CONCLUSION Evolving therapy , including the incorporation of biologic agents , has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma . The apparent plateau in the FFS curve , starting approximately 8 to 10 years from the beginning of treatment , raises the issue of the potential curability of these patients The recognition of several new types of non-Hodgkin 's lymphoma ( NHL ) in recent years has led to proposals for changing lymphoma classifications , including a new proposal put forth by the International Lymphoma Study Group ( ILSG ) . However , the clinical significance of the new entities and the practical utility of this new proposal have not been studied . Therefore , we performed a clinical evaluation of the ILSG classification . A cohort of 1,403 cases of NHL was organized at nine study sites around the world and consisted of consecutive patients seen between 1988 and 1990 who were previously untreated . A detailed protocol for histologic and clinical analysis was followed at each site , and immunologic characterization as to T- or B-cell phenotype was required . Five expert hematopathologists visited the sites and each classified each case using the ILSG classification . A consensus diagnosis was also reached in each case , and each expert re review ed a 20 % r and om sample of the cases . Clinical correlations and survival analyses were then performed . A diagnosis of NHL was confirmed in 1,378 ( 98.2 % ) of the cases . The most common lymphoma types were diffuse large B-cell lymphoma ( 31 % ) and follicular lymphoma ( 22 % ) , whereas the new entities comprised 21 % of the cases . Diagnostic accuracy was at least 85 % for most of the major lymphoma types , and reproducibility of the diagnosis was 85 % . Immunophenotyping improved the diagnostic accuracy by 10 % to 45 % for a number of the major types . The clinical features of the new entities were distinctive . Both the histologic types and the patient characteristics as defined by the International Prognostic Index predicted for patient survival . In conclusion we found that the ILSG classification can be readily applied and identifies clinical ly distinctive types of NHL . However , for clinical application , prognostic factors as defined by the International Prognostic Index must be combined with the histologic diagnosis for appropriate clinical decisions Background . In a prospect i ve r and omized manner , this study evaluated the effect of adjuvant chemotherapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone ; CHOP ) in patients with Stage I non‐Hodgkin lymphoma ( NHL ) who have achieved a complete response ( CR ) after radiation therapy ( RT ) PURPOSE Although rituximab ( R ) is commonly used for patients with advanced follicular lymphoma ( FL ) requiring treatment , the optimal associated chemotherapy regimen has yet to be clarified . PATIENTS AND METHODS We conducted an open-label , multicenter , r and omized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide , vincristine , and prednisone ( CVP ) or six cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) or six cycles of fludarabine and mitoxantrone ( FM ) . The principal end point of the study was time to treatment failure ( TTF ) . RESULTS There were 534 patients enrolled onto the study 
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None showed benefit to ACR regarding OS , yet there was a trend in favor of anthracyclines for disease control .
ACR improved disease control , as measured by PFS and RD with an increased risk for side effects , notably cardiotoxicity .