***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 investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation ( HCT-ASCT ) in relapsed/refractory ( r/r ) primary central nervous system lymphoma ( PCNSL ) , we conducted a single-arm multicentre study for immunocompetent patients ( < 66 years ) with PCNSL failing high-dose methotrexate)-based chemotherapy .  Induction consisted of two courses of rituximab ( 375 mg/m2 ) , high-dose cytarabine ( 2 × 3 g/m2 ) and thiotepa ( 40 mg/m2 ) with collection of stem cells in between . Conditioning for HCT-ASCT consisted of rituximab 375 mg/m2 , carmustine 400 mg/m2 and thiotepa ( 4 × 5 mg/kg ) . Patients commenced HCT-ASCT irrespective of response after induction . Patients not achieving complete remission ( CR ) after HCT-ASCT received whole-brain radiotherapy . Primary end point was CR after HCT-ASCT . We enrolled 39 patients ; median age and Karnofsky performance score are 57 years and 90 % , respectively . About 28 patients had relapsed and 8 refractory disease . About 22 patients responded to induction and 32 patients commenced HCT-ASCT . About 22 patients ( 56.4 % ) achieved CR after HCT-ASCT . Respective 2-year progression-free survival ( PFS ) and overall survival ( OS ) rates were 46.0 % ( median PFS 12.4 months ) and 56.4 % ; median OS not reached . We recorded four treatment-related deaths . Thiotepa-based HCT-ASCT is an effective treatment option in eligible patients with r/r PCNSL . Comparative studies are needed to further scrutinise the role of HCT-ASCT in the salvage setting Treatment of primary central nervous system lymphoma ( PCNSL ) improved in recent years . However , the high neurotoxicity and low survival rates associated with this condition remain unresolved . We report 13 consecutive patients with PCNSL for whom upfront melphalan , cyclophosphamide , etoposide , and dexamethasone ( known as LEED ) followed by autologous stem-cell transplantation ( ASCT ) was planned at the Anjo Kosei Hospital . All patients were pathologically diagnosed with diffuse large B-cell lymphoma and were negative for human immunodeficiency virus . All patients were to receive three cycles of high-dose methotrexate-based induction chemotherapy , two cycles of high-dose AraC-based chemotherapy , and LEED followed by ASCT . All 13 patients achieved a partial response , and the 3-year overall survival ( OS ) rate was 76.2 % . Seven of the 13 patients were alive at the last follow-up , without any adverse events , including neurotoxicity . Six of the 13 ( 46.2 % ) patients underwent ASCT and the 3-year OS rate was 80.0 % . Although this study included only a limited number of patients , these preliminary signs of efficacy and tolerability merit further consideration . To make further improvements in survival , the rate of patients undergoing ASCT should be increased . Other prospect i ve studies involving greater numbers of patients are required to confirm these findings BACKGROUND High-dose methotrexate-based chemotherapy is st and ard for primary CNS lymphoma , but most patients relapse . High-dose chemotherapy with autologous stem cell transplantation ( HCT-ASCT ) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS . We aim ed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma . METHODS In this prospect i ve , single-arm , phase 2 trial , we recruited patients aged 18 - 65 years with newly diagnosed primary CNS lymphoma and immunocompetence , with no limitation on clinical performance status , from 15 hospitals in Germany . Patients received five courses of intravenous rituximab 375 mg/m(2 ) ( 7 days before first high-dose methotrexate course and then every 10 days ) and four courses of intravenous high-dose methotrexate 8000 mg/m(2 ) ( every 10 days ) and then two courses of intravenous rituximab 375 mg/m(2 ) ( day 1 ) , cytarabine 3 g/m(2 ) ( days 2 and 3 ) , and thiotepa 40 mg/m(2 ) ( day 3 ) . 3 weeks after the last course , patients commenced intravenous HCT-ASCT ( rituximab 375 mg/m(2 ) [ day 1 ] , carmustine 400 mg/m(2 ) [ day 2 ] , thiotepa 2 × 5 mg/kg [ days 3 and 4 ] , and infusion of stem cells [ day 7 ] ) , irrespective of response status after induction . We restricted radiotherapy to patients without complete response after HCT-ASCT . The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment . This trial is registered at Clinical Trials.gov , number NCT00647049 . FINDINGS Between Jan 18 , 2007 , and May 23 , 2011 , we recruited 81 patients , of whom two ( 2 % ) were excluded , therefore we included 79 ( 98 % ) patients in the analysis . All patients started induction treatment ; 73 ( 92 % ) commenced HCT-ASCT . 61 ( 77·2 % [ 95 % CI 66·1 - 86·6 ] ) patients achieved a complete response . During induction treatment , the most common grade 3 toxicity was anaemia ( 37 [ 47 % ] ) and the most common grade 4 toxicity was thrombocytopenia ( 50 [ 63 % ] ) . During HCT-ASCT , the most common grade 3 toxicity was fever ( 50 [ 68 % ] of 73 ) and the most common grade 4 toxicity was leucopenia ( 68 [ 93 % ] of 73 ) . We recorded four ( 5 % ) treatment-related deaths ( three [ 4 % ] during induction and one [ 1 % ] 4 weeks after HCT-ASCT ) . INTERPRETATION HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma , but further comparative studies are needed . FUNDING University Hospital Freiburg and Amgen The optimum treatment of primary CNS lymphoma ( PCNSL ) is not yet determined . The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy ( HDT ) with autologous stem cell transplantation ( ASCT ) in patients with newly diagnosed PCNSL . Twenty-five patients received two courses of initial chemotherapy combining methotrexate , etoposide , carmustine and methylprednisolone , and one course of ifosfamide – cytarabine followed by peripheral stem cell collection .  Seventeen responsive patients then received HDT using carmustine , etoposide , cytarabine and melphalan with autologous stem cell rescue . After ASCT for responding patients or after salvage therapy for non-responders , whole brain radiation therapy at a dose of 30 Gy was delivered . The objective response rate to the induction chemotherapy was 84 % . Four of the 21 responding patients did not have ASCT because of toxicity or refusal . With a median follow-up time of 34 months , the projected event free survival rate is 46 % at 4 years . Projected overall survival is 64 % at 4 years . Sixteen patients are actually in continuous complete response . No evidence of late treatment-related toxicity was observed . This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias BACKGROUND We investigated the efficacy and safety of t and em high-dose methotrexate ( HD-MTX ) induction followed by high-dose busulfan/thiotepa ( HD-BuTT ) with autologous peripheral blood stem-cell transplantation ( aPBSCT ) and response-adapted whole-brain radiation therapy ( WBRT ) in patients with newly diagnosed primary central nervous system lymphoma . PATIENTS AND METHODS Twenty-three patients were treated with HD-MTX on days 1 and 10 . In case of at least a partial remission ( PR ) , HD-BuTT followed by aPBSCT was given . Patients without response to induction or without complete remission ( CR ) after HD-BuTT received WBRT . RESULTS Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13 % . CR/PR rates for all patients ( n = 23 ) were 70%/13 % . There were three deaths during therapy . With longer follow-up three neurotoxic deaths occurred in irradiated patients ( n = 9 ) , while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT . At a median follow-up of 15 months ( range 1 - 69 ) median event-free survival ( EFS ) and overall survival ( OS ) for all patients were 17 and 20 months ( Kaplan-Meier ) , after HD-BuTT 27 months and " not reached " , respectively . Estimated 2-year EFS and OS were 45 % and 48 % for all patients versus 56 % and 61 % for the HD-BuTT group , respectively . CONCLUSION MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen . Median survival for patients treated with high-dose chemotherapy is not reached yet . The induction regimen needs optimisation . In this study WBRT was associated with a high incidence of severe neurotoxicity High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma ( PCNSL ) , but relapses remain frequent . High-dose chemotherapy ( HDC ) with autologous stem-cell transplant ( ASCT ) may provide an alternative to address chemoresistance and overcome the blood-brain barrier . In this single-center phase-2 study , newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab , methotrexate ( 3.5 g/m(2 ) ) , procarbazine , and vincristine ( R-MPV ) . Those with a complete or partial response proceeded with consolidation HDC with thiotepa , cyclophosphamide , and busulfan , followed by ASCT and no radiotherapy . Primary end point was 1-year progression-free survival ( PFS ) , N = 32 . Median age was 57 , and median Karnofsky performance status 80 . Following R-MPV , objective response rate was 97 % , and 26 ( 81 % ) patients proceeded with HDC-ASCT . Among all patients , median PFS and overall survival ( OS ) were not reached ( median follow-up : 45 months ) . Two-year PFS was 79 % ( 95 % confidence interval [ CI ] , 58 - 90 ) , with no events observed beyond 2 years . Two-year OS was 81 % ( 95 % CI , 63 - 91 ) . In transplanted patients , 2-year PFS and OS were 81 % . There were 3 treatment-related deaths . Prospect i ve neuropsychological evaluations suggested relatively stable cognitive functions posttransplant . In conclusion , this treatment was associated with excellent disease control and survival , an acceptable toxicity profile , and no evidence of neurotoxicity thus far . This trial was registered at www . clinical trials.gov as NCT00596154 BACKGROUND Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas , but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven . We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma . METHODS This open , r and omised , phase 2 trial was undertaken in 24 centres in six countries . 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS , cranial nerves , or eyes , aged 18 - 75 years , and with Eastern Cooperative Oncology Group performance status of 3 or lower and meas 
    Output:
    
Subgroup analysis showed that the use of carmustine and thiotepa as a conditioning regimen carried the lowest risk of transplant‐related mortality .
The thiotepa , busulfan , and cyclophosphamide regimen , on the other h and , showed numerically superior OS and PFS rates .
This systematic review and meta‐ analysis provides estimates response and survival after ASCT and suggests improved rates compared to the historical data