***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 The monoclonal anti-CD20 antibody rituximab , combined with chemotherapeutic agents , has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia ( CLL ) but not in those with coexisting conditions . We investigated the benefit of the type 2 , glycoengineered antibody obinutuzumab ( also known as GA101 ) as compared with that of rituximab , each combined with chlorambucil , in patients with previously untreated CLL and coexisting conditions . METHODS We r and omly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale ( CIRS ) ( range , 0 to 56 , with higher scores indicating worse health status ) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil , obinutuzumab plus chlorambucil , or rituximab plus chlorambucil . The primary end point was investigator-assessed progression-free survival . RESULTS The patients had a median age of 73 years , creatinine clearance of 62 ml per minute , and CIRS score of 8 at baseline . Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil , as compared with chlorambucil monotherapy , increased response rates and prolonged progression-free survival ( median progression-free survival , 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio for progression or death , 0.18 ; 95 % confidence interval [ CI ] , 0.13 to 0.24 ; P<0.001 ; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio , 0.44 ; 95 % CI , 0.34 to 0.57 ; P<0.001 ) . Treatment with obinutuzumab-chlorambucil , as compared with chlorambucil alone , prolonged overall survival ( hazard ratio for death , 0.41 ; 95 % CI , 0.23 to 0.74 ; P=0.002 ) . Treatment with obinutuzumab-chlorambucil , as compared with rituximab-chlorambucil , result ed in prolongation of progression-free survival ( hazard ratio , 0.39 ; 95 % CI , 0.31 to 0.49 ; P<0.001 ) and higher rates of complete response ( 20.7 % vs. 7.0 % ) and molecular response . Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil , but the risk of infection was not increased . CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions . In this patient population , obinutuzumab was superior to rituximab when each was combined with chlorambucil . ( Funded by F. Hoffmann-La Roche ; Clinical Trials.gov number , NCT01010061 . ) PURPOSE Genomic features including unmutated immunoglobulin variable region heavy chain ( IgVH ) genes , del(11q22.3 ) , del(17p13.1 ) , and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia ( CLL ) . In addition , ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome . PATIENTS AND METHODS We prospect ively evaluated the prognostic significance of a comprehensive panel of laboratory factors on both response and progression-free survival ( PFS ) using sample s and data from 235 patients enrolled onto a therapeutic trial . Patients received either fludarabine ( FL ; n = 113 ) or fludarabine plus cyclophosphamide ( FC ; n = 122 ) as part of a US Intergroup r and omized trial for previously untreated CLL patients . RESULTS Complete response ( CR ) rates were 24.6 % for patients receiving FC and 5.3 % for patients receiving FL ( P = .00004 ) . PFS was statistically significantly longer in patients receiving FC ( median , 33.5 months for patients receiving FC and 19.9 months for patients receiving FL ; P < .0001 ) . The occurrence of del(17p13.1 ) ( hazard ratio , 3.428 ; P = .0002 ) or del(11q22.3 ) ( hazard ratio , 1.904 ; P = .006 ) was associated with reduced PFS . CR and overall response rates were not significantly different based on cytogenetics , IgVH mutational status , CD38 expression , or p53 mutational status . Expression of ZAP-70 , Bcl-2 , Bax , Mcl-1 , XIAP , Caspase-3 , and Traf-1 was not associated with either clinical response or PFS . CONCLUSION These results support the use of interphase cytogenetic analysis , but not IgVH , CD38 expression , or ZAP-70 status , to predict outcome of FL-based chemotherapy . Patients with high-risk cytogenetic features should be considered for alternative therapies BACKGROUND On the basis of promising results that were reported in several phase 2 trials , we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia . METHODS Treatment-naive , physically fit patients ( aged 30 - 81 years ) with CD20-positive chronic lymphocytic leukaemia were r and omly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine ( 25 mg/m(2 ) per day ) and cyclophosphamide ( 250 mg/m(2 ) per day ) for the first 3 days of each 28-day treatment course with or without rituximab ( 375 mg/m(2 ) on day 0 of first course , and 500 mg/m(2 ) on day 1 of second to sixth courses ) in 190 centres in 11 countries . Investigators and patients were not masked to the computer-generated treatment assignment . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00281918 . FINDINGS 408 patients were assigned to fludarabine , cyclophosphamide , and rituximab ( chemoimmunotherapy group ) and 409 to fludarabine and cyclophosphamide  ( chemotherapy group ) ; all patients were analysed . At 3 years after r and omisation , 65 % of patients in the chemoimmunotherapy group were free of progression compared with 45 % in the chemotherapy group ( hazard ratio 0·56 [ 95 % CI 0·46 - 0·69 ] , p<0·0001 ) ; 87 % were alive versus 83 % , respectively ( 0·67 [ 0·48 - 0·92 ] ; p=0·01 ) . Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia ( 136 [ 34 % ] of 404 vs 83 [ 21 % ] of 396 ; p<0·0001 ) and leucocytopenia ( 97 [ 24 % ] vs 48 [ 12 % ] ; p<0·0001 ) . Other side-effects , including severe infections , were not increased . There were eight ( 2 % ) treatment-related deaths in the chemoimmunotherapy group compared with ten ( 3 % ) in the chemotherapy group . INTERPRETATION Chemoimmunotherapy with fludarabine , cyclophosphamide , and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia . Moreover , the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia . FUNDING F Hoffmann-La Roche PURPOSE CAMPATH-1H is a human immunoglobulin G1 ( IgG1 ) anti-CD52 monoclonal antibody ( MAb ) that binds to nearly all B- and T-cell lymphomas and leukemias . We report the results of a multicenter phase II trial that used CAMPATH-1H in previously chemotherapy-treated patients with chronic lymphocytic leukemia ( CLL ) . MATERIAL S AND METHODS Twenty-nine patients who had relapsed after an initial response ( n = 8) or were refractory ( n = 21 ) to chemotherapy were treated with CAMPATH-1H administered as a 30-mg 2-hour intravenous ( IV ) infusion thrice weekly for a maximum period of 12 weeks . RESULTS Eleven patients ( 38 % ) achieved a partial remission ( PR ) and one ( 4 % ) a complete remission ( CR ) ( response rate , 42 % ; 95 % confidence interval [ CI ] , 23 % to 61 % ) . Three of eight patients ( 38 % ) with a relapse and nine of 21 refractory patients ( 43 % ) responded to CAMPATH-1H therapy . CLL cells were rapidly eliminated from blood in 28 of 29 patients ( 97 % ) . CR in the bone marrow was obtained in 36 % and splenomegaly resolved completely in 32 % . Lymphadenopathy was normalized in only two patients ( 7 % ) . The median response duration was 12 months ( range , 6 to 25 + ) . World Health Organization ( WHO ) grade IV neutropenia and thrombocytopenia developed in three ( 10 % ) and two patients ( 7 % ) , respectively . Neutropenia and thrombocytopenia recovered in most responding patients during continued CAMPATH-1H treatment . Lymphopenia ( < 0.5 x 10(9)/L ) occurred in all patients . Two patients had opportunistic infections and four had bacterial septicemia . CONCLUSION CAMPATH-1H had significant activity in patients with advanced and chemotherapy-resistant CLL . The most pronounced effects were noted in blood , bone marrow , and spleen . Preferential clearance of blood may allow harvesting of uncontaminated blood stem cells for use in high-dose chemotherapy protocol PURPOSE This phase II pilot study determined the efficacy and safety of alemtuzumab ( Campath-1H ; Burroughs Wellcome , United Kingdom ) in patients with chronic lymphocytic leukemia ( CLL ) , all of whom had previously received fludarabine and other chemotherapy regimens . PATIENTS AND METHODS Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States . The target dose of 30 mg over 2 hours , three times weekly , was administered for up to 16 weeks . Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria . Safety assessment s included analysis of lymphocyte sub population s. Antimicrobial prophylaxis was not m and atory . RESULTS Eight patients ( 33 % ) achieved a major response ( all partial remissions ) , with a median time to response of 3.9 months ( range , 1.6 to 5.3 months ) . The median duration of response was 15.4 months ( range , 4.6 to > or= 38.0 months ) , the median time to disease progression was 19.6 months ( range , 7.7 to > or= 42.0 months ) , and the median survival time was 35.8 months ( range , 8.8 to > or= 47.1 months ) . Acute infusion-related events , mainly grade s 1 and 2 , were most common and most severe in the first week . Ten patients ( eight nonresponders and two responders ) experienced major infections on- study . Pneumocystis carinii pneumonia was reported in two patients on- study ; neither had received prophylaxis . Median CD4 + and CD8 + counts decreased and then began to increase by the end of the study , with further recovery by 1-month follow-up . One of 53 sample s obtained from 10 patients had a low titer of alemtuzumab antibodies . CONCLUSION Alemtuzumab has significant activity in poor-prognosis , fludarabine-treated CLL patients . However , because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia , future protocol s should include m and atory prophylaxis BACKGROUND Rituximab has been successfully used as an experimental therapy in different autoimmune diseases . Recently , a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease . However , like with any immunosuppressive therapy , there is a concern of opportunistic viral reactivations with the use of rituximab , including herpes and polyomaviruses . OBJECTIVES To study the incidence of new infections and reactivations with BK , JC , Epstein-Barr and cytomegalovirus ( B 
    Output:
    
Patients treated with FCR showed significantly higher neutropenia and serious adverse reactions .