***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
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    Input: BACKGROUND To assess the activity and toxicity of 2-chlorodeoxyadenosine ( cladribine , CDA ) given by subcutaneous bolus injections to patients with hairy cell leukemia ( HCL ) . PATIENTS AND METHODS Sixty-two eligible patients with classic or prolymphocytic HCL ( 33 non-pretreated patients , 15 patients with relapse after previous treatment , and 14 patients with progressive disease during a treatment other than CDA ) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days . Response status was repeatedly assessed according to the Consensus Resolution criteria . RESULTS Complete and partial remissions were seen in 47 ( 76 % ) and 13 ( 21 % ) patients , respectively , for a response rate of 97 % . All responses were achieved with a single treatment course . Most responses occurred early ( i.e. within 10 weeks ) after start of CDA therapy , but response quality improved during weeks and even months after treatment completion . The median time to treatment failure for all patients was 38 months . Leukopenia was the main toxicity . Granulocyte nadir ( median 0.2 x 10(9)/l ) was strongly associated with the incidence of infections ( P = 0.0013 ) . Non-specific lymphopenia occurred early after CDA treatment , and normal lymphocytes recovered slowly over several months . No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte sub population . No opportunistic infections were observed . CONCLUSIONS One course of CDA given by subcutaneous bolus injections is very effective in HCL . The subcutaneous administration is more convenient for patients and care providers , and has a similar toxicity profile to continuous intravenous infusion . The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA Although the nucleoside analogs cladribine and pentostatin produce high response rates in patients with hairy cell leukemia ( HCL ) , a significant number of patients eventually relapse . Several studies have demonstrated that patients with complete remission ( CR ) have a longer disease-free survival . Therefore , strategies to improve on the initial response to nucleoside analog therapy are likely to be beneficial , at least for a proportion of patients . We have treated 13 patients with newly diagnosed HCL ( n = 11 ) or after failure of one prior chemotherapy ( n = 2 ) with cladribine ( 5.6 mg/m(2 ) given intravenously over 2 hours daily for 5 days ) followed by 8 weekly doses of rituximab ( 375 mg/m(2 ) ) . All patients achieved a CR and minimal residual disease ( MRD ) assessed by consensus primer polymerase chain reaction ( PCR ) or flow cytometry was eradicated in 11 ( 92 % ) of 12 and in 12 ( 92 % ) of 13 of patients , respectively . There was no decline in the absolute CD4 and CD8 lymphocyte number after rituximab . We conclude that eradication of MRD in HCL is possible . Whether this leads to a reduced risk of relapse would need to be evaluated in a larger number of patients and with longer follow-up . Disease characteristics may potentially be used to identify patients that are more likely to benefit from such additional therapy Cladribine ( 2-chlorodeoxyadenosine , 2-CdA ) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia ( HCL ) . In search of the optimal mode of 2-CdA administration , 132 patients with untreated HCL were r and omized to receive either st and ard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic . Analysis of treatment response confirmed similar complete remission rates , overall response rates , progression-free survival , and overall survival in both 2-CdA protocol s. However , we did not observe lower toxicity in the weekly schedule . Of special interest , no significant differences were found in the rate of grade 3/4 infections ( 18 % for daily and 26 % for weekly protocol , difference -8.2 % ; 95 % confidence interval [ CI ] -23.2 % to 6.9 % ; P = .28 ) and the rate of septic deaths ( 3 % for daily and 2 % for weekly protocol , difference 1.4 % ; 95 % CI -4.3 % to 7.0 % ; P = .64 ) . In conclusion , HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the st and ard 5-day 2-CdA protocol 2-Chlorodeoxyadenosine ( 2-CdA ) , a purine analog , has become universally accepted as the agent of choice in treating hairy cell leukemia ( HCL ) . However , few studies have reported long-term outcomes after 2-CdA treatment . Between January 1990 and June 2003 , 86 consecutive patients with HCL were treated with a single 7-day course of 2-CdA by continuous infusion at a dose of 0.1 mg/kg per day . Of the 86 patients ( mean age : 49 years ) , 67 patients ( 79 % ) achieved a complete remission ( CR ) ; 18 patients ( 21 % ) achieved a partial remission ( PR ) ; and 1 patient 's response was unable to be assessed . The progression-free survival ( PFS ) for initial relapse after 12 years was 54 % . At a median follow-up of 9.7 years ( range , 0.3 - 13.8 years ) , 31 ( 36 % ) of 85 patients relapsed . There were 23 relapsed patients treated with a second cycle of 2-CdA ; 2 patients were treated with alternative agents ; and 6 patients were observed . Of the 23 relapsed patients retreated with 2-CdA , 12 ( 52 % ) achieved a CR and 7 ( 30 % ) patients achieved a PR ( overall response rate : 83 % ) . The overall survival ( OS ) rate after 12 years was 87 % . There were 15 patients ( 17 % ) who developed other malignancies . Long-term follow-up of up to 14 years ( median : 9.7 years ) showed an excellent PFS and OS for HCL patients after 2-CdA treatment The Eastern Cooperative Oncology Group conducted a study of pentostatin ( 2'-deoxycoformycin ) in 37 patients with hairy-cell leukemia . Among the 27 patients who met all the study 's entry criteria , the response rate was 96 percent , with 16 patients ( 59 percent ) entering complete remission and 10 patients ( 37 percent ) partial remission . In one patient no response was observed . These results were not significantly changed by the inclusion of nine additional patients who were found retrospectively not to have fulfilled the entry criteria . When complete remission was attained , maintenance therapy was not given . Despite this , no patient has had a relapse , and the duration of complete remission ranges from 1 to 375 days . Pentostatin appears to be equally effective in untreated patients and in those who have progressive disease after splenectomy or after both splenectomy and treatment with interferon . Whether pentostatin is superior to splenectomy or interferon as therapy for hairy-cell leukemia will have to be assessed by direct comparison in r and omized studies . Lengthy follow-up will be required to determine a median duration for the responses of hairy-cell leukemia to pentostatin Nucleoside analogues are highly active in patients with hairy cell leukaemia ( HCL ) ; however , patients continue to relapse . This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL ( N = 59 ) , relapsed HCL ( N = 14 ) and HCL variant ( HCLv , N = 7 ) . Cladribine 5·6 mg/m2 was given intravenously ( IV ) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks . Complete response rate in patients with untreated HCL , relapsed HCL and HCLv was 100 % , 100 % and 86 % , respectively . With a median follow up of 60 months , 5‐year failure‐free survival ( FFS ) in patients with untreated HCL , relapsed HCL and HCLv was 95 % , 100 % and 64 % , respectively . Median duration of response  to the cladribine followed by rituximab was significantly longer than the first‐line cladribine single agent in patients who received this treatment as second‐line treatment ( 72 months vs not reached , P = 0·004 ) . Almost all patients ( 94 % ) achieved negative minimal residual disease ( MRD ) after the treatment . Positive MRD during the follow up did not necessarily result in clinical ly relevant relapse . Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv , and can achieve durable remission Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies PURPOSE To conduct a phase II trial in chemoresistant hairy cell leukemia ( HCL ) with BL22 , a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL . PATIENTS AND METHODS Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts . Patients were stratified into three groups : response to cladribine less than 1 year , those with a response lasting 1 to 4 years , or no response and uncontrolled infection . Patients received BL22 40 microg/kg every other day for three doses on cycle 1 . Those achieving hematologic remission ( HR ) , defined as neutrophils > or = 1,500/mm(3 ) , hemoglobin > or = 11 g/dL , and platelets > or = 100,000/mm(3 ) , were observed . Patients without HR were re-treated at 30 microg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1 . RESULTS Thirty-six patients were enrolled including 26 , nine , and one in groups 1 to 3 . The response after one cycle ( CR , 25 % ; PR , 25 % ) improved when 56 % were re-treated ( CR , 47 % ; PR , 25 % ) . CR rate was similar in groups 1 and 2 ( P = .7 ) . Twenty-two with baseline spleen height lower than 200 mm had higher CR ( 64 % v 21 % ; P = .019 ) and OR rates ( 95 % v 36 % ; P = .0002 ) compared to 14 with spleens either absent or higher than 200 mm . The only serious toxicity was reversible grade 3 hemolytic uremic syndrome , not requiring plasmapheresis , in two patients ( 6 % ) . High neutralizing antibodies were observed in four patients ( 11 % ) and prevented re-treatment . CONCLUSION BL22 activity in HCL is confirmed . Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy Hairy cell leukemia ( HCL ) is an indolent B-cell neoplasm , strongly expressing CD20 . Despite initial very high response rates following cladribine , many patients ( pts ) ultimately relapse . Having relapsed after prior treatment with cladribine , 24 HCL pts ( 21 male , 3 female ) with a median age of 53.5 years were treated with rituximab at 375 mg/m2 intravenously weekly for 4 weeks . Of the pts , 3 ( 13 % ) achieved complete remissions and 3 ( 13 % ) , partial responses . Thus , 6 ( 25 % ) of 24 pts achieved a response following rituximab . At a median follow-up of 14.6 months , 2 responders have relapsed ; median time to relapse was not yet reached . The only grade III or IV toxicities demonstrated were culture-negative febrile neutropenia , transient and reversible disseminated intravascular coagulation related to rituximab administration , and a diverticular abscess , each in single patients . Of 18 nonresponders , 9 pts subsequently received other treatments ; 5 pts were retreated with cladribine , 3 underwent splenectomy , and 1 received pentostatin . Follow-up data are available on 7 of these 9 patients ; all 7 patients achieved improvements in hematologic parameters .  Rituximab , administered at this dose and schedule , has only modest single-agent activity in cladribine-failed HCL patients when compared with other agents active in this disease The purpose of this study was to investigate the efficacy and safety of the monoclonal antibody , rituximab , in relapsed or refractory hairy cell leukemia ( HCL ) . Fifteen patients with relapsed or primary refractory HCL after nucleoside analogs received rituximab 375 mg/m2 weekly for a total of 8 planned doses . An additional 
    Output:
    
The most effective therapy in patients treatment naïve and in first relapse was cladribine with rituximab maintenance