***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: We design ed a new treatment protocol incorporating concurrent administration of L-asparaginase ( to reduce the probability of systemic progression during concurrent chemoradiotherapy ( CCRT ) ) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma , nasal type ( ENKTL ) .  CCRT comprised  radiation ( 36–44 Gy ) with weekly cisplatin ( 30 mg/m2 ) and tri-weekly L-asparaginase ( 4 000 IU ) . Chemotherapy — MIDLE ( methotrexate 3 g/m2 on day 1 , etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2–3 , dexamethasone 40 mg on days 1–4 , and L-asparaginase 6 000 IU/m2 on days 4 , 6 , 8 , 10)—was repeated every 28 days for two cycles . One of the 28 patients  developed distant lesions after CCRT . The final complete response rate was 82.1 % . Four patients dropped out during or after their first MIDLE cycle due to toxicities ( recurrent G3 hyperbilirubinemia [ n = 1 ] , G3 - 5 increased creatinine [ n = 2 ] , and G5 infection [ n = 1 ] ) . With a median follow-up of 46 months ( 95 % CI : 39–47 months ) , the estimated 3-year progression-free survival rate and overall survival rate were 74.1 % and 81.5 % , respectively . This MIDLE protocol may be effective for localized ENKTL . However , concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits Extranodal natural killer/T‐cell lymphoma ( ENKTL ) , nasal‐type , is a distinct entity of lymphoid tissue . ENKTL is sensitive to radiotherapy ( RT ) , but the prognosis is poorer than for other types of early lymphoma . The treatment schedule is controversial The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma ( NKTCL ) remains to be established . A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively review ed . Among the patients with stage I – II disease , 58.3 % received radiotherapy ( RT ) ± chemotherapy , and 41.7 % received chemotherapy alone . Compared with chemotherapy alone , RT ± chemotherapy elicited a significantly higher overall response rate ( ORR ) ( 100 vs. 57.1 % , P < 0.001 ) and substantially prolonged 5-year overall survival ( OS ) ( 55.3 vs. 18.0 % , P < 0.001 ) in patients with stage I – II disease . Compared with other chemotherapeutic regimens , pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin ( GELOX ) was associated with a significantly higher ORR ( 92.9 vs. 51.6 % , P = 0.009 ) and a significantly improved 5-year OS ( 78.6 vs. 23.9 % , P = 0.010 ) in patients with stage I – II disease . Nine patients with stage I – II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome ( 5-year OS 100 % , 5-year progression-free survival ( PFS ) 85.7 % ) , which was superior to that of patients receiving other regimens followed by RT . In conclusion , RT played an important role for elderly patients with early-stage NKTCL , and the PGEMOX/GELOX regimen was superior to other regimens . The combination of them may be a promising treatment option The aim of this study was to investigate the impact of the induction treatment with SMILE ( dexamethasone , methotrexate , ifosfamide , l-asparaginase , and etoposide ) chemotherapy and consolidation with upfront autologous stem cell transplantation ( ASCT ) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma ( ENKTL ) . We analyzed the treatment response to SMILE and toxicity , and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospect i ve cohort studies . The median age of patients was 45 years ( range : 17–65 years ) , and all patients had disseminated disease . The overall response rate to SMILE induction treatment was 59 % ( 16/27 ) including nine complete responses . However , five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE . Eleven patients could undergo ASCT , and there was no transplantation-related mortality . The survival outcome of patients underwent ASCT was better than patients who could not ( P < 0.05 ) . However , four patients relapsed even after ASCT , thus , the median overall survival was 10.6 months , and the median progression-free survival was 5.1 months . Pretreatment Epstein – Barr virus ( EBV ) DNA titer was only independent prognostic factor for overall survival . In conclusion , our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL . However , considering frequent occurrences of disease relapse and treatment-related mortality , additional efforts are required to improve treatment outcomes of stage IV ENKTL patients PURPOSE To explore a more effective treatment for newly diagnosed stage IV , relapsed , or refractory extranodal natural killer/T-cell lymphoma , nasal type ( ENKL ) , we conducted a phase II study of the steroid ( dexamethasone ) , methotrexate , ifosfamide , L-asparaginase , and etoposide ( SMILE ) regimen . PATIENTS AND METHODS Patients with newly diagnosed stage IV , relapsed , or refractory disease and a performance status of 0 to 2 were eligible . Two cycles of SMILE chemotherapy were administered as the protocol treatment . The primary end point was the overall response rate ( ORR ) after the protocol treatment . RESULTS A total of 38 eligible patients were enrolled . The median age was 47 years ( range , 16 to 67 years ) , and the male : female ratio was 21:17 . The disease status was newly diagnosed stage IV in 20 patients , first relapse in 14 patients , and primary refractory in four patients . The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections . No treatment-related deaths were observed after the revision . The ORR and complete response rate after two cycles of SMILE chemotherapy were 79 % ( 90 % CI , 65 % to 89 % ) and 45 % , respectively . In the 28 patients who completed the protocol treatment , 19 underwent hematopoietic stem-cell transplantation . The 1-year overall survival rate was 55 % ( 95 % CI , 38 % to 69 % ) . Grade 4 neutropenia was observed in 92 % of the patients . The most common grade 3 or 4 nonhematologic complication was infection ( 61 % ) . CONCLUSION SMILE chemotherapy is an effective treatment for newly diagnosed stage IV , relapsed or refractory ENKL . Myelosuppression and infection during the treatment should be carefully managed Circulating Epstein-Barr virus ( EBV ) DNA is a biomarker of EBV-associated malignancies . Its prognostic value in early stage NK/T-cell lymphoma ( NKTCL ) in the era of asparaginase was investigated . 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6Gy ( range 50–60Gy ) radiation .  The amount of EBV-DNA was prospect ively measured in both pretreatment and post-treatment plasma sample s by real-time quantitative PCR . At the end of treatment , complete response ( CR ) rate was 79.4 % , and overall response rate ( ORR ) was 88.2 % . Patients with negative pretreatment EBV-DNA had a higher CR rate ( 96.0 % vs. 69.8 % , p = 0.023 ) . The 3-year progression-free survival ( PFS ) rate and overall survival ( OS ) rate was 71 % and 83 % , respectively . In multivariate survival analysis , post-treatment EBV-DNA positivity and treatment response ( non-CR ) were prognostic factors for both worse PFS and OS ( p < 0.05 ) . Local tumor invasion was also a prognostic factor for worse OS ( p = 0.010 ) . In patients with CR , post-treatment EBV-DNA positivity correlated with inferior PFS and OS ( both p < 0.0001 ) . In patients with positive pretreatment EBV-DNA , negative post-treatment EBV-DNA correlated with better PFS and OS ( both p < 0.0001 ) . These findings indicate that post-treatment EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase , and may be used as an indicator of minimal residual disease We conducted a phase II trial of concurrent chemoradiotherapy ( CCRT ) followed by 2 cycles of l-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma ( ENKTL ) .  CCRT consisted of 40–44 Gy of radiotherapy with weekly administration of 30 mg/m2 of cisplatin for 4 weeks . Two cycles of VIDL ( etoposide ( 100 mg/m2 ) , ifosfamide ( 1,200 mg/m2 ) , and dexamethasone ( 40 mg ) from days 1 to 3 , and l-asparaginase ( 4,000 IU/m2 ) every other day from days 8 to 20 ) were administered sequentially . CCRT yielded a 90 % overall response rate without significant side effects in 30 patients , including 20 patients with complete response ( CR ) ; however , two patients showed distant disease progression . After CCRT , VIDL chemotherapy showed an 87 % final CR rate ( 26/30 ) . Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy  , no treatment-related mortality was observed , and l-asparaginase-associated toxicity was manageable . With a median follow-up of 44 months , 11 patients showed local ( n = 4 ) and distant ( n = 7 ) relapse or progression . The estimated 5-year progression-free and overall survival rates were 73 and 60 % , respectively . In conclusion , CCRT followed by l-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL Purpose To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T –cell lymphoma ( ENKTL ) , we conducted a prospect i ve phase II study of L-asparaginase , cyclophosphamide , vincristine , doxorubicin and dexamethasone ( CHOP-L ) regimen in combination with radiotherapy . Patients and methods Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment . Treatment included 6–8 cycles of CHOP-L ( cyclophosphamide , 750 mg/m2 day 1 ; vincristine , 1.4 mg/m2 day 1 ( maximal dose 2 mg ) , doxorubicin 50 mg/m2 day 1 ; dexamethasone 10 mg days 1–8 ; L-asparaginase 6000 u/m2 days 2–8 ) . Radiotherapy was scheduled after 4–6 cycles of CHOP-L regimen , depending on stage and primary anatomic site . The primary endpoint was complete response ( CR ) rate . Results A total of 38 eligible patients were enrolled . The median age was 40.5 years ( range , 15 to 71 years ) . Their clinical characteristics were male to female ratio , 24:14 ; Ann Arbor stage I , 20 ; II , 11 ; III , 3 ; IV , 4 . CR and overall response rates were 81.6 % ( 95 % CI , 69.3 % to 93.9 % ) and 84.2 % , respectively . With a median follow-up of 25 months , the 2-year overall survival , progression-free survival and disease-free survival rates were 80.1 % ( 95%CI , 73.3 % to 86.9 % ) , 81 % ( 95%CI , 74.5 % to 87.5 % ) and 93.6 % ( 95%CI , 89.3 % to 97.9 % ) , respectively . The major adverse events were myelosuppression , liver dysfunction , and digestive tract toxicities . Grade 3 to 4 leukopenia and neutropenia were 76.3 % and 84.2 % , respectively . No treatment-related death was observed . Conclusion CHOP-L chemotherapy in combination 
    Output:
    
CONCLUSIONS ASP-based CT  significantly improved ORR and CR in patients with newly diagnosed both early-stage and advanced-stage ENKTL