***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: BACKGROUND We compared a regimen of six chemotherapeutic agents administered sequentially at high doses , followed by myeloablative treatment and bone marrow transplantation , with a regimen of methotrexate , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ) as initial or salvage treatment for adults with diffuse large-cell lymphoma . METHODS Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were r and omly assigned to receive either MACOP-B ( 50 patients ) or high-dose sequential therapy ( 48 patients ) . The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group . RESULTS After a median follow-up of 55 months , the patients given high-dose sequential therapy , as compared with those treated with MACOP-B , had significantly higher rates of complete response ( 96 percent vs. 70 percent , P=0.001 ) , freedom from disease progression ( 84 percent vs. 49 percent , P<0.001 ) , freedom from relapse ( 88 percent vs. 70 percent , P=0.055 ) , and event-free survival ( 76 percent vs. 49 percent , P=0.004 ) . The difference in overall survival at seven years , which also favored the group assigned to high-dose sequential therapy , was marginally significant ( 81 percent vs. 55 percent , P=0.09 ) . CONCLUSIONS High-dose sequential therapy is superior to st and ard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type The combination of cyclophosphamide , doxorubicin , vincristine , and prednisone , given every 3 weeks ( CHOP-21 ) is st and ard chemotherapy for aggressive lymphomas . To determine whether CHOP given every 2 weeks ( CHOP-14 ) or the addition of etoposide ( CHOEP-21 , CHOEP-14 ) can improve results in patients ages 18 to 60 years with good prognosis ( normal lactic dehydrogenase [ LDH ] level ) , 710 patients were r and omized to 6 cycles of CHOP-21 , CHOP-14 , CHOEP-21 ( CHOP plus etoposide 100 mg/m2 days 1 - 3 ) , or CHOEP-14 in a 2 x 2 factorial study design . Patients in the biweekly regimens received granulocyte colony-stimulating factor ( G-CSF ) starting from day 4 . Patients received radiotherapy ( 36 Gy ) to sites of initial bulky disease and extranodal disease . CHOEP achieved better complete remission ( 87.6 % versus 79.4 % ; P = .003 ) and 5-year event-free survival rates ( 69.2 % versus 57.6 % ; P = .004 , primary end point ) than CHOP , whereas interval reduction improved overall survival ( P = .05 ; P = .044 in the multivariate analysis ) . Although the CHOEP regimens induced more myelosuppression , all regimens were well tolerated .  CHOEP should be the preferred chemotherapy regimen for young patients with good-prognosis ( normal LDH level ) aggressive lymphoma Cyclophosphamide , doxorubicin , vincristine , and prednisone , given every 3 weeks ( CHOP-21 ) , is st and ard chemotherapy for aggressive lymphomas . To determine whether biweekly CHOP ( CHOP-14 ) with or without etoposide is more effective than CHOP-21 , 689 patients ages 61 to 75 years were r and omized to 6 cycles of CHOP-21 , CHOP-14 , CHOEP-21 ( CHOP plus etoposide 100 mg/m2 days 1 - 3 ) , or CHOEP-14 . Patients in the 2-weekly regimens received granulocyte colony-stimulating factor ( G-CSF ) starting from day 4 . Patients received radiotherapy ( 36 Gy ) to sites of initial bulky disease and extranodal disease . Complete remission rates were 60.1 % ( CHOP-21 ) , 70.0 % ( CHOEP-21 ) , 76.1 % ( CHOP-14 ) , and 71.6 % ( CHOEP-14 ) . Five-year event-free and overall survival rates were 32.5 % and 40.6 % , respectively , for CHOP-21 and 43.8 % and 53.3 % , respectively , for CHOP-14 . In a multivariate analysis , the relative risk reduction was 0.66 ( P = .003 ) for event-free and 0.58 ( P < .001 ) for overall survival after CHOP-14 compared with CHOP-21 . Toxicity of CHOP-14 and CHOP-21 was similar , but CHOEP-21 and in particular CHOEP-14 were more toxic . Due to its favorable efficacy and toxicity profile , CHOP-14 should be considered the new st and ard chemotherapy regimen for patients ages 60 or older with aggressive lymphoma From July 1984 to September 1987 , 737 patients with aggressive malignant lymphoma ( ML ) were treated by an intensive regimen ( LNH-84 ) comprising three or four courses of doxorubicin , 75 mg/m2 ; cyclophosphamide , 1,200 mg/m2 ; vindesine , 2 mg/m2 x 2 ; bleomycin , 10 mg x 2 ; and prednisolone , 60 mg/m2 x 5 ( ACVB ) , consolidation with high-dose methotrexate , ifosfamide , etoposide , asparaginase , and cytarabine , and a r and omized late intensification with two courses of cytarabine , cyclophosphamide , teniposide , bleomycin , and prednisone ( AraCVmB ) .  Four hundred forty-two patients had intermediate- grade ML , 221 high grade ML , and 74 unclassified ML . Most of the patients had advanced disease : stage IIE ( 23 % ) , III ( 13 % ) , or IV ( 47 % ) ; 38 % disseminated nodes ; 38 % two or more extranodal sites ; and 41 % a tumoral mass greater than 10 cm . Five hundred fifty-three patients ( 75 % ) went into complete remission ( CR ) , 63 ( 9 % ) into partial remission , 62 ( 8 % ) failed to respond , and 59 ( 8 % ) died during ACVB courses , 17 of them from progression of the disease . With a median follow-up of 23 months , the estimated 2-year overall survival time to failure ( TTF ) , and time to relapse ( TTR ) survival are 67 % , 56 % , and 67 % , respectively . Patients receiving a late intensification had the same relapse rate as the other patients . A persistent fibronecrotic mass was found in 150 patients ( 20 % ) and did not influence the relapse rate . Toxicity was mainly neutropenia and infection during the ACVB courses , with 40 patients ( 5 % ) dying from septic complications while responding to treatment . Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L , 58 % fever ( 6 % grade 4 ) , and 49 % a documented infection ( 8 % grade 4 ) . These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML Rituximab , a chimeric monoclonal antibody that binds specifically to the CD20 antigen , induced objective responses in 50 % of patients with low- grade or follicular B-cell lymphoma . Because most nonfollicular B-cell lymphomas also express the CD20 antigen , we conducted a phase II study to evaluate the efficacy and tolerability of this new agent in patients with more aggressive types of lymphoma . Patients with diffuse large B-cell lymphoma ( DLCL ) , mantle cell lymphoma ( MCL ) , or other intermediate- or high- grade B-cell lymphomas according to the Working Formulation were included in this prospect i ve r and omized phase II study if they were in first or second relapse , if they were refractory to initial therapy , if they progressed after a partial response to initial therapy , or if they were elderly ( age > 60 years ) and not previously treated . The patients received 8 weekly infusions of rituximab at the dose of 375 mg/m2 in arm A or one infusion of 375 mg/m2 followed by 7 weekly infusions of 500 mg/m2 in arm B. Patients were evaluated 2 months after the last rituximab infusion . Fifty-four patients were r and omized from 9 centers in Europe and Australia ( 28 in arm A and 26 in arm B ) . A total of 5 complete responses ( CR ) and 12 partial responses ( PR ) were observed among the 54 enrolled patients , with no difference between the two doses . In an intent-to-treat analysis , the CR rate was 9 % ( CI95 % , 3 % to 20 % ) and the PR rate was 22 % ( CI95 % , 12 % to 36 % ) , for an overall response rate of 31 % ( CI95 % , 20 % to 46 % ) . An analysis of prognostic factors showed that response rates were lower in patients with refractory disease , patients with lymphoma not classified as DLCL , and patients with a tumor larger than 5 cm in diameter . DLCL and MCL patients had response rates of 37 % and 33 % , respectively . The median time to progression exceeded 246 days for the 17 responding patients . The most frequently reported adverse events were related to an infusion syndrome and were mild : 19 % of the patients had a grade 3 related adverse event , slightly more in arm B , and only 1 patient had a grade 4 related adverse event in arm A. Two patients ( 3.7 % ) withdrew from treatment because of severe adverse events , one patient in each arm . In this first trial of rituximab in DLCL and MCL , patients experienced a significant clinical activity with a low toxicity .  Rituximab has significant activity in DLCL and MCL patients and should be tested in combination with chemotherapy in such patients BACKGROUND High-dose chemoradiotherapy combined with autologous bone marrow transplantation can cure patients with disseminated , aggressive non-Hodgkin 's lymphoma in whom first-line chemotherapy has failed . In contrast , cure is rare with second-line chemotherapy . It has been suggested that patients with slow responses to the initial phase of first-line chemotherapy are at high risk for relapse . Therefore , such patients are potential c and i date s for early bone marrow transplantation . METHODS To investigate whether patients with slow responses , defined as only a partial response after three courses of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP )  , would benefit from early transplantation , we conducted a prospect i ve , r and omized trial . The early application of high-dose chemoradiotherapy and autologous bone marrow transplantation was compared with the continuation of CHOP therapy for another five courses . Patients with complete responses after three courses of CHOP ( fast responses ) and patients who responded partially but still had tumor-positive marrow continued with another five courses of CHOP . The study end points were the response rate , overall survival , disease-free survival , and event-free survival . RESULTS Of 286 patients who could be evaluated for the rapidity of their response after three courses of CHOP  , 38 percent had fast responses , 47 percent had slow responses , and 15 percent had no response . Among 106 patients with slow responses who had lymphoma-negative marrow , 69 patients ( 65 percent ) were r and omized . Seventy-four percent of the CHOP group and 68 percent of the transplantation group had complete remissions ( P = 0.54 ) . At four years the rates of overall , disease-free , and event-free survival were 85 , 72 , and 53 percent , respectively , in the CHOP group and 56 , 60 , and 41 percent in the transplantation group ( P > 0.10 ) . The disease-free survival in both groups did not differ significantly from that of nonr and omized patients with fast responses ( 54 percent at four years ) . CONCLUSIONS The early application of high-dose , marrow-ablative chemoradiotherapy with autologous bone marrow transplantation does not improve the outcome in patients with aggressive non-Hodgkin 's lymphoma that responds slowly to first-line CHOP chemotherapy 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 radi 
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However , HDT did not have an effect on OS , when compared to conventional chemotherapy .
Despite higher CR rates , there is no benefit for high-dose chemotherapy with stem cell transplantation as a first line treatment in patients with aggressive NHL