***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 Pre-transplantation (18)F-fluorodeoxyglucose ( FDG ) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant ( HDT/ASCT ) for patients with relapsed or refractory Hodgkin 's lymphoma . In this study , we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin , followed by augmented ifosfamide , carboplatin , and etoposide ( ICE ) . METHODS In this non-r and omised , open-label , single-centre , phase 2 trial , we enrolled patients with relapsed or refractory Hodgkin 's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen . All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1 , 8 , and 15 for two 28 day cycles . After completion of brentuximab vedotin treatment , patients received a PET scan . Patients who achieved PET-negative status ( a Deauville score of 1 or 2 ) proceeded directly to HDT/ASCT ; those with persistent abnormalities on PET received two cycles of augmented ICE ( augICE ; two doses of ifosfamide 5000 mg/m(2 ) in combination with mesna 5000 mg/m(2 ) continuous infusion over 24 h , days 1 and 2 ; one dose of carboplatin AUC 5 , day 3 ; three doses of etoposide 200 mg/m(2 ) every 12 h , day 1 ) before consideration for HDT/ASCT . Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE ; however , all patients in the intention-to-treat population were assessed for the primary outcome , which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE . This study is registered with Clinical Trials.gov , number NCT01508312 , and is no longer accruing patients . FINDINGS Between Jan 5 , 2012 , and Oct 4 , 2013 , we enrolled 46 patients . One patient was deemed ineligible , and not evaluable , before treatment initiation owing to having nodular , lymphocyte-predominant Hodgkin 's lymphoma and thus 45 patients received treatment .  After brentuximab vedotin , 12 patients ( 27 % , 95 % CI 13 - 40 ) were PET-negative and proceeded to HDT/ASCT . 33 ( 73 % , 95 % CI 60 - 86 ) patients were PET-positive after brentuximab vedotin ; one PET-positive patient withdrew consent , therefore 32 PET-positive patients received augICE , 22 ( 69 % , 95 % CI 53 - 85 ) of whom were PET-negative . Overall , 34 patients ( 76 % , 95 % CI 62 - 89 ) achieved PET-negativity . All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT . Brentuximab vedotin was well tolerated and associated with few grade 3 - 4 adverse events including hyperglycaemia ( two [ 4 % ] patients , grade 3 ) , nausea ( one [ 2 % ] , grade 3 ) , hypoglycaemia ( one [ 2 % ] , grade 3 and one [ 2 % ] , grade 4 ) , and hypocalcaemia ( one [ 2 % ] , grade 3 and one [ 2 % ] , grade 4 ) . INTERPRETATION PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE result ed in a high proportion of patients with relapsed or refractory Hodgkin 's lymphoma achieving PET-negativity , and therefore could optimise the chance of cure after HDT/ASCT . FUNDING Seattle Genetics Hodgkin lymphoma ( HL ) prognostic models based on factors measured at time of autologous hematopoietic cell transplantation ( AHCT ) are limited by small sample sizes . Models based on information at diagnosis are often not uniformly collected or available at transplantation . We propose an easily implementable prognostic model for progression-free survival ( PFS ) post-AHCT based on factors available at transplantation in a large international cohort of HL patients . The outcomes of 728 AHCT recipients for relapsed/refractory HL were studied . Patients were r and omly selected for model development ( n = 337 ) and validation ( n = 391 ) . The multivariate model identified 4 major adverse risk factors at the time of AHCT with the following relative weights : Karnofsky performance score < 90 and chemotherapy resistance at AHCT were each assigned 1 point , whereas at least 3 chemotherapy regimens pre-AHCT and extranodal disease at AHCT were each assigned 2 points . Based on the total score summed for the 4 adverse risk factors , 3 risk groups were identified : low ( score = 0 ) , intermediate ( score = 1 to 3 ) , or high ( score = 4 to 6 ) . The 4-year PFS for the low- ( n = 176 ) , intermediate- ( n = 261 ) , and high- ( n = 283 ) risk groups were 71 % ( 95 % confidence interval [ CI ] , 63 % to 78 % ) , 60 % ( 95 % CI , 53 % to 66 % ) , and 42 % ( 95 % CI , 36 % to 49 % ) , respectively . The prognostic model was vali date d in an independent cohort . The Center for International Blood and Marrow Transplant Research model is based on factors easily available at the time of AHCT and discriminates patients with favorable post-AHCT outcomes as well as an intermediate-risk group . This model should assist in the prospect i ve evaluation of alternative treatment strategies BACKGROUND High-dose chemotherapy followed by transplantation of autologous haemopoietic stem cells ( BEAM-HSCT ) is frequently used to treat patients with relapsed Hodgkin 's disease . We aim ed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation ( Dexa-BEAM ) . METHODS 161 patients between 16 and 60 years of age with relapsed Hodgkin 's disease were r and omly assigned two cycles of Dexa-BEAM ( dexamethasone and carmustine , etoposide , cytarabine , and melphalan ) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells . Only patients with chemosensitive disease ( complete or partial remission after two courses of Dexa-BEAM ) proceeded to further treatment . The primary endpoint was freedom from treatment failure for patients with chemosensitive disease . Analysis was per protocol . FINDINGS 17 patients were excluded from the study after r and omisation ( ten given Dexa-BEAM and seven given BEAM-HSCT ) . Median follow-up was 39 months ( IQR 3 - 78 ) . Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT ( 55 % ) than for those on Dexa-BEAM ( 34 % ; difference -21 % , 95 % CI -39.87 to -2.13 ; p=0.019 ) . Overall survival of patients given either treatment did not differ significantly . INTERPRETATION High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin 's disease irrespective of length of initial remission PURPOSE High-dose chemotherapy ( HDCT ) followed by autologous stem-cell transplantation ( PBSCT ) has become the st and ard treatment for patients with relapsed Hodgkin 's lymphoma ( HL ) . The intensity of treatment needed is unclear . This European intergroup study evaluated the impact of sequential high-dose chemotherapy ( SHDCT ) before myeloablative therapy . PATIENTS AND METHODS Patients with histologically confirmed , relapsed HL were treated with two cycles of dexamethasone , cytarabine , and cisplatin , and those without disease progression were r and omly assigned . In the st and ard arm ( A ) , patients received myeloablative therapy with carmustine , BEAM ( carmustine , etoposide , cytarabine , and melphalan ) followed by PBSCT . Patients in the experimental arm ( B ) also received sequential cyclophosphamide , methotrexate , and etoposide in high-doses before BEAM .  Freedom from treatment failure ( FFTF ) was the primary end point . Remission rates , overall survival ( OS ) , and toxicity of treatment were secondary end points . RESULTS From a total of 284 patients included , 241 responding patients were r and omly assigned after two cycles of dexamethasone , cytarabine , and cisplatinum . Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations ( P < .05 ) . Mortality was similar in both arms ( 20 % and 18 % ) . With a median observation time of 42 months , there was no significant difference in terms of FFTF ( P = .56 ) and OS ( P = .82 ) between arms . FFTF at 3 years was 62 % ( 95 % CI , 56 % to 68 % ) and OS was 80 % ( 95 % CI , 75 % to 85 % ) . Patients with stage IV , early relapse , multiple relapse , anemia , or B symptoms had a higher risk of recurrence ( P < .001 ) . CONCLUSION Compared with conventional high-dose chemotherapy , additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL More active high-dose chemotherapy ( HDC ) regimens are needed for refractory Hodgkin 's lymphoma ( HL ) . We report a cohort analysis of 180 consecutive patients with primary refractory or poor-risk relapsed HL treated with busulfan-melphalan ( Bu-Mel ) ( n = 39 ) , gemcitabine-busulfan-melphalan ( Gem-Bu-Mel ) ( n = 84 ) , or BEAM ( BCNU , etoposide , ara-C , melphalan ; n = 57 ) between 2005 and 2010 . Their pre-HDC positron emission tomography ( PET ) scans were interpreted prospect ively . Despite more prevalent poor-risk features in the Gem-Bu-Mel cohort , such as PET-positive tumors at HDC , tumors growing at HDC , extranodal disease , or bulky tumors at prior relapse , this cohort had improved outcomes compared with the Bu-Mel and BEAM cohorts , with event-free survival ( EFS ) rates of 57 % , 33 % , and 39 % , respectively ( P = .01 ) , at median follow-up of the whole population of 36 months ( range , 3 to 72 ) . Their respective overall survival ( OS ) rates were , respectively , 82 % , 52 % , and 59 % ( P = .04 ) . Secondary acute myelogenous leukemia was seen in 5 patients after BEAM but was not seen in Gem-Bu-Mel and Bu-Mel cohorts ( P = .004 ) . Multivariate analyses showed independent adverse effects of an HDC regimen different from Gem-Bu-Mel ( hazard ratio [ HR ] for EFS = 2.3 , P = .0008 ; HR for OS = 2.7 , P = .0005 ) , positive PET at HDC ( HR for EFS = 2.2 , P = .004 , HR for OS = 3.1 , P = .0001 ) , and > 1 previous salvage line ( HR for EFS = 1.9 , P = .008 , HR for OS = 1.8 , P = .07 ) . Gem-Bu-Mel improved outcomes in this cohort analysis of patients with refractory/poor-risk relapsed HL and merits evaluation in r and omized phase III trials This study was set up to demonstrate whether prognostic classification based on the secondary age-adjusted International Prognostic Index ( sAA-IPI ) for recurring aggressive non-Hodgkin lymphoma ( NHL ) or the prognostic score for recurring Hodgkin lymphoma ( HL ) can be improved by including the midtreatment results of fluorine-18-fluorodeoxy-glucose-positron emission tomography ( FDG-PET ) . Clinical data on patients with recurring lymphoma who were treated with second-line chemotherapy ( DHAP-VIM-DHAP ) followed by autologous stem cell transplantation ( ASCT ) were collected and combined with the results of FDG-PET performed before and after 2 cycles of reinduction chemotherapy . PET responses after 2 courses were scored as complete remission ( CR ) , partial remission ( PR ) , or no response ( NR ) . A multivariate analysis was performed to design a predictive model . The number of patients ( 101 of 117 ) included those ( 78 patients with aggressive NHL and 23 patients with HL ) that could be analyzed according to protocol . Of these , 80 patients were chemosensitive and 77 received transplants . Both secondary clinical risk score ( P<.001 ) and  
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In conclusion , the moderate quality evidence suggests pretransplant FDG-PET to have value in predicting outcome in refractory/relapsed Hodgkin lymphoma patients treated with autologous SCT .
Nevertheless , a considerable proportion of pretransplant FDG-PET positive patients remains disease free and a considerable proportion of pretransplant FDG-PET negative patients develops disease relapse after autologous SCT