***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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    ***EXAMPLES*** 
    Input: PURPOSE Intraocular lymphoma ( IOL ) frequently coexists with primary central nervous system lymphoma(PCNSL ) . We sought to determine the efficacy of high-dose methotrexate ( MTX ) alone in patients with IOL . We also sought to determine whether micromolar levels of MTX could be achieved in the aqueous and vitreous humor of the eye after i.v . administration of the drug . EXPERIMENTAL DESIGN Nine patients with concurrent PCNSL and IOL or isolated IOL were treated with MTX alone . All patients were treated with i.v . 8 g/m(2 ) MTX . MTX concentrations in serum , aqueous humor , and vitreous humor were obtained in seven of nine patients with IOL and in one additional patient with PCNSL but no evidence of IOL . RESULTS Micromolar concentrations of MTX  were present in both ocular chambers 4 h after completion of the infusion in eight of eight patients . Levels of MTX  were lower in the vitreous humor compared with the aqueous humor in five of six patients in whom both chambers were assayed . Initial response of IOL to MTX was demonstrated by seven of nine patients ( six complete responses and one partial response ) , whereas two patients had persistent IOL despite achievement of micromolar concentrations of MTX . In the patients with concurrent PCNSL and IOL , seven of seven had complete responses in the brain after treatment with MTX . Three of seven patients with initial response of IOL experienced relapse in the eye requiring orbital radiation , and four of nine patients had sustained response of IOL to MTX . CONCLUSIONS A subset of patients with IOL may experience sustained remission when treated with high-dose i.v . MTX alone . Although micromolar MTX concentrations are present in the eye 4 h after infusion , the lower concentration achieved in vitreous humor may contribute to persistence of IOL BACKGROUND To improve survival of elderly patients with primary central nervous system lymphoma ( PCNSL ) , we conducted a phase II study with high-dose methotrexate ( MTX ) combined with procarbazine and CCNU . To reduce neurotoxicity , whole-brain irradiation was reserved for patients not responding to chemotherapy . PATIENTS AND METHODS High-dose MTX was applied on days 1 , 15 , and 30 , procarbazine on days 1 - 10 , and CCNU on day 1 . Study treatment comprised up to three 45-day cycles . There was no lower limit of Karnofsky performance status ( KPS ) . RESULTS Thirty patients with PCNSL ( n = 29 ) or primary ocular lymphoma ( n = 1 ) were included ( median age 70 years , range 57 - 79 years ) . The median initial KPS was 60 % ( range 30%-90 % ) . Best documented response in 27 assessable patients were 12 of 27 ( 44.4 % ) complete remissions , 7 of 27 ( 25.9 % ) partial remissions , and 8 of 27 ( 29.6 % ) disease progressions . Two patients died of probable treatment-related causes . With a median follow-up of 78 months ( range 34 - 105 ) , the 5-year overall survival is 33 % . Eight of 30 patients ( 26.7 % ) are currently alive and well , six without signs of leukoencephalopathy . CONCLUSION The combination of high-dose MTX with procarbazine and CCNU is feasible and effective and results in a low rate of leukoencephalopathy . Comorbidity and toxicity remain of concern when treating PCNSL in elderly patients BACKGROUND The dose of high-dose methotrexate ( HDMTX ) in elderly patients often has to be reduced , result ing in a loss of treatment efficacy . We evaluated HDMTX-related toxicity with special regard to age distribution in patients with primary central nervous system lymphoma ( PCNSL ) in a phase IV multicenter trial . PATIENTS AND METHODS One hundred and fifty-four patients ( median age 61 years ; 89 patients > 60 years old , 21 patients > 70 years old ) received 619 HDMTX cycles . Toxicity was evaluated prospect ively using the WHO classification . Unless a reduced dose was required after calculating a decreased glomerular filtration rate ( GFR ) , the patients received 4 g/m(2 ) HDMTX followed by leucovorin rescue . RESULTS Toxicity was generally mild with toxicities of WHO grade > or =3 usually < 10 % . The differences in the incidence and severity of toxicity were not statistically significant between patients > 60 years and < or = 60 years old . The same was true for therapy termination owing to MTX toxicity and for delayed serum MTX clearance . Dose reduction significantly differed between patients < or = 60 years and those > 60 years old ( 18 % versus 44 % ; P = 0.001 ) . CONCLUSIONS HDMTX is a safe treatment for PCNSL patients regardless of age , with adherence to dose reduction determined by calculating the GFR before each treatment cycle 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 measurable disease were central ly r and omly assigned by computer to receive four courses of either methotrexate 3.5 g/m(2 ) on day 1 ( n=40 ) or methotrexate 3.5 g/m(2 ) on day 1 plus cytarabine 2 g/m(2 ) twice a day on days 2 - 3 ( n=39 ) . Both regimens were administered every 3 weeks and were followed by whole-brain irradiation . The primary endpoint was complete remission rate after chemotherapy . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00210314 . FINDINGS All r and omly assigned participants were analysed . After chemotherapy , seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission , with a complete remission rate of 18 % ( 95 % CI 6 - 30 ) and 46 % ( 31 - 61 ) , respectively , ( p=0.006 ) . Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response , with an overall response rate of 40 % ( 25 - 55 ) and 69 % ( 55 - 83 ) , respectively , ( p=0.009 ) . Grade 3 - 4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group ( 36 [ 92 % ] vs six [ 15 % ] ) . Four patients died of toxic effects ( three vs one ) . INTERPRETATION In patients aged 75 years and younger with primary CNS lymphoma , the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone . FUNDING Swiss Cancer League PURPOSE To improve survival and reduce toxicity in primary CNS lymphoma ( PCNSL ) treatment , we conducted a multicenter phase II study with early high-dose chemotherapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) followed by hyperfractionated whole-brain radiotherapy ( WBRT ) for newly diagnosed PCNSL patients younger than 65 years of age . PATIENTS AND METHODS Chemotherapy included three steps : three cycles of methotrexate ( 8 g/m2 ) ; cytarabine ( AraC ; two doses of 3 g/m2 ) and thiotepa ( 40 mg/m2 ) followed by stem-cell harvest ; HDT with carmustine ( 400 mg/m2 ) and thiotepa ( two doses of 5 mg/kg body weight ) followed by ASCT . WBRT ( 45 Gy , two doses of 1 Gy/d ) was administered for consolidation . RESULTS Thirty patients with PCNSL younger than 65 years of age ( median , 54 years ; range , 27 years to 64 years ) were enrolled ( nine pilot-phase ; 21 phase II ) . Twenty-eight patients responded to methotrexate : six patients with complete remission ( CR ) , 15 patients with partial remission ( PR ) , and seven patients with stable disease ( SD ) with clinical improvement . Of 26 patients proceeding to AraC and thiotepa , 10 patients achieved CR , 14 patients achieved PR , one patient experienced SD with clinical improvement , and one patient suffered disease progression . Twenty-three patients received HDT plus ASCT , result ing in 15 patients with CRs and eight patients with PRs . After WBRT , 21 of 21 patients had CRs . One patient died from liver failure after methotrexate . HDT was well tolerated apart from WHO grade 3/4 cytopenia . With a median follow-up of 63 months ( range , 4 months to 84 months ) , 5-year overall survival probability is 69 % for all patients and 87 % for the 23 patients receiving HDT plus ASCT . The 5-year probability of relapse-related death is 21 % for all patients ( n = 30 ) and 8.7 % for patients treated with HDT plus ASCT ( n = 23 ) . CONCLUSION Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL In anticipation of a consortium study of methotrexate ( MTX ) therapy provided to patients with primary central nervous system lymphoma ( PCNSL ) we have provided intravenous MTX without irradiation therapy to 31 non-immunosuppressed individuals . Twenty ( 65 % ) achieved complete response and 11 ( 35 % ) partial response to therapy . For the 31 patients the median survival was 30.43 months with an actuarial median follow up time of 30.69 months . The 2 + year survival was 63 % for all patients and 90 % for complete responders . Of 375 drug cycles , grade 3 leukopenia was identified in 3 cycles , mucositis in 6 cycles and delayed drug clearance in 47 cycles . Recurrences included brain ( 9/20 ) and /or spinal fluid ( 2/20 ) . The median Karnofsky scale improved from 40 ( 10–80 ) prior to therapy to 90 after treatment . Eleven patients , in complete response for a median of 22 + months after diagnosis were evaluated using 4 instruments that assess Quality of Life Functional Assessment of Cancer Therapy – Brain ( FACT-BR ) modified , Symptom Question naire , Social Adjustment Scale-Self-Report and Problem Solving Inventory . Their psychosocial adjustment , well-being and stress coping abilities were comparable to the normative groups . Further there was no evidence of any MTX-induced , Magnetic Resonance Imaging (MRI)-detected encephalopathy in these individuals and there was preservation of clinical cognition and memory . We conclude that therapy with MTX , without radiation can be used in PCNSL patients without limitations of age or pretreatment Karnofsky scores . Further rates of response and median survival approach those of therapies using multiple drugs and radiation , but with a less likely risk of dementia BACKGROUND Primary central nervous system lymphoma ( PCNSL ) is an aggressive extranodal non-Hodgkin lymphoma confined to the central nervous system . In this article , we report the results of a pilot trial adding rituximab to the established regimen consisting of methotrexate , procarbazine , and lomustine ( R-MCP ) . DESIGN AND METHODS PCNSL patients ≥65 years without Karnofsky performance score ( KPS ) limit were included .  R-MCP regimen consisted of rituximab ( 375 mg/m(2 ) i.v . on days -6 , 1 , 15 , and 29 ) , methotrexate ( 3 g/m(2 ) i.v . , days 2 , 16 , and 30 ) followed by folinic rescue , procarbazine ( 60 mg/m(2 ) orally , days 2 - 11 ) , and lomustine ( 110 mg/m(2 ) orally , day 2 ) . A maximum of three 43-day cycles were applied . Primary end point was response to treatment obtained by magnetic resonance imaging . Secondary end points were overall survival ( OS ) and progression-free survival ( PFS ) . RESULTS Twenty-eight patients were included ( median age 75 , median KPS 60 % ) . Best documented response : complete remission in 18 of 28 ( 64 % ) , partial remission in 5 of 28 ( 18 % ) , stable disease in 1 of 28 ( 4 % ) , and progressive disease in 2 of 28 ( 7 % ) patients . Response was not assessed in two patients . Two treatment-associated 
    Output:
    
AEs , especially infective complications , hepatotoxicity and haematological toxicities , were assessed more often in patients undergoing HD-MTX therapy combined with cytarabine .
However , the risk of severe infections and toxicity was significantly higher in patients treated with combined chemotherapy .