***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: To compare efficacy and toxicity of a sequential HDCT and a st and ard HDCT  in patients with histologically confirmed relapsed Hodgkin ’s disease . Primary endpoint of the study is freedom from treatment failure ( FFTF ) in both treatment arms . Secondary endpoints are complete remission ( CR ) , complete remission unconfirmed ( CRu ) rates 3 months after end of protocol , relapse-free survival ( RFS ) , overall survival ( OS ) , frequency of severe toxicities ( WHO grade 3 or 4 ) , and secondary neoplasia . Study 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 To investigate whether combined-modality treatment ( CMT ) with two cycles of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) followed by extended-field radiotherapy ( EF-RT ) is superior to EF-RT alone in patients with early favorable Hodgkin 's lymphoma ( HL ) . PATIENTS AND METHODS Between 1993 and 1998 , 650 patients with newly diagnosed , histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and r and omly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field ( arm A ) or two cycles of ABVD followed by the same radiotherapy ( arm B ) . Results At a median observation time of 87 months , there was no difference between treatment arms in terms of complete response rate ( arm A , 95 % ; arm B , 94 % ) and overall survival ( at 7 years : arm A , 92 % ; arm B , 94 % ; P = .43 ) . However , freedom from treatment failure was significantly different , with 7-year rates of 67 % in arm A ( 95 % CI , 61 % to 73 % ) and 88 % in arm B ( 95 % CI , 84 % to 92 % ; P < or= .0001 ) . This was due mainly to significantly more relapses after EF-RT only ( arm A , 22 % ; arm B , 3 % ) . No patient treated with CMT experienced relapse before year 3 . Relapses were treated mainly with bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone , or with the combination cyclophosphamide , vincristine , procarbazine , and prednisone/ABVD ;  treatment of relapse was significantly more successful in arm A than in arm B ( P = .017 ) . In total , there were 39 second malignancies , with 21 in arm A and 18 in arm B , respectively . The incidence was approximately 0.8 % per year during years 2 to 9 and was highest in older patients ( P < .0001 ) and those with " B " symptoms ( P = .012 ) . CONCLUSION CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone PURPOSE To evaluate prospect ively the feasibility and efficacy of early intensive therapy , including intensified cytoreductive chemotherapy ( CT ) and high-dose CT ( HDCT ) followed by autologous stem-cell transplantation ( ASCT ) , in patients with advanced Hodgkin 's disease ( HD ) who failed to respond completely or relapsed after initial treatment . PATIENTS AND METHODS Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial , all 157 patients with induction failure ( IF ) ( n = 67 ) , partial response ( PR ) of less than 75 % ( n = 22 ) , or relapse ( n = 68 ) were included in this study . Planned salvage therapy included mitoguazone , ifosfamide , vinorelbine , and etoposide monthly for two to three cycles followed by high-dose carmustine , etoposide , cytarabine , and melphalan with ASCT . RESULTS With a median follow-up of 50 months , the 5-year survival estimates were 30 % , 72 % , and 76 % for the IF , PR , and relapse groups , respectively ( P = .0001 ) , 71 % for the 101 patients given HDCT , and 32 % for the 48 patients treated without HDCT ( P = .0001 ) . Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression , salvage without HDCT , and chemoresistant disease before HDCT were significantly associated with shorter overall survival . CONCLUSION Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors . However , for patients with IF and chemoresistant disease , this approach remains unsatisfactory BACKGROUND Gemcitabine ( difluorodeoxycytidine ) is active as a single agent in Hodgkin 's disease and has been used successfully in combination with cisplatin to treat a variety of solid tumors . PATIENTS AND METHODS We evaluated the combination of gemcitabine/dexamethasone/cisplatin ( GDP ) as salvage chemotherapy in 23 patients with relapsed or refractory Hodgkin 's disease ( median age 36 years , range 19 - 57 ) . Treatment consisted of gemcitabine 1000 mg/m(2 ) intravenously on days 1 and 8 , dexamethasone 40 mg orally days 1 - 4 and cisplatin 75 mg/m(2 ) on day 1 , every 21 days as an outpatient . Response was assessed following two cycles of treatment . RESULTS There were four complete responses and 12 partial responses for a response rate of 69.5 % ( 95 % confidence interval 52 % to 87 % ) ; the remaining seven patients had stable disease and no patient progressed on treatment . All patients had successful stem cell mobilization and underwent transplantation with a median 10.6 x 10(6 ) CD34 + cells/kg . Hematological toxicity from GDP was mild ( grade 3 neutropenia 8.6 % , grade 3 thrombocytopenia 13 % ) . CONCLUSIONS In summary , GDP is an active regimen for patients with relapsed or refractory Hodgkin 's disease . The response rate is similar to the rates of other current salvage regimens , it can be given to out patients with tolerable toxicity and it does not inhibit the mobilization of autologous stem cells 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 The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma , that is , those not responding to conventional-dose chemotherapy at the time of transplant , have been poor . The relapse rate has been high after autologous bone marrow transplant , whereas allogeneic transplantation has been associated with excessive transplant-related toxicity . Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease ( GVHD ) . This syndrome , named autologous graft-versus-host disease , has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as gamma-interferon and interleukin-2 . A r and omized , prospect i ve study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine , and augmented by the administration of gamma-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas . Fifty-one patients were r and omized , 24 to the autologous GVHD induction arm , and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell ( PBSC ) grafts . There were no differences in treatment-related mortality , overall and event-free survival ( OS , EFS ) between both groups ; however , in the induction arm , GVHD developed only in 4 patients . The administration of oral cyclosporine followed by interleukin-2 and gamma-interferon is generally not well tolerated , and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation ( ABMT ) are increasingly used for the treatment of relapsed and resistant Hodgkin 's disease , although there has been no r and omised trial of this treatment . The British National Lymphoma Investigation therefore undertook a r and omised comparison of high-dose chemotherapy ( BEAM = carmustine , etoposide , cytarabine , and melphalan ) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue ( mini-BEAM ) in patients with active Hodgkin 's disease , for whom conventional therapy had failed . 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM . All have been followed up for at least 12 months ( median 34 months ) . 5 BEAM recipients have died ( 2 from causes related to ABMT and 3 from disease progression ) compared with 9 mini-BEAM recipients ( all disease progression ) . This difference was not significant ( p = 0.318 ) . However , both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT ( p = 0.025 and p = 0.005 , respectively ) . Recruitment to the trial became increasingly difficult because patients refused r and omisation and requested ABMT . It was therefore closed early ( 40 patients rather than 66 intended ) . Nevertheless , we found a dose-response effect in these patients with relapsed and resistant Hodgkin 's disease . High doses facilitated by ABMT can lead to better disease-free survival BACKGROUND AND OBJECTIVES Response to pre-transplant salvage chemotherapy remains the most important prognostic factor 
    Output:
    
The currently available evidence suggests a PFS benefit for patients with relapsed or refractory HL after first-line therapy , who are treated with HDCT followed by ASCT compared to patients treated with conventional chemotherapy .
Intensifying the HDCT regime before HDCT followed by ASCT did not show a difference as compared to HDCT followed by ASCT , but was associated with increased adverse events