***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: This phase II study determined the efficacy and safety of alemtuzumab , a humanized anti-CD52 monoclonal antibody , delivered subcutaneously as first-line therapy , over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia ( B-CLL ) . Injections were administered subcutaneously 3 times per week , from week 2 to 3 onward . An overall response rate ( OR ) of 87 % ( 95 % CI , 76%-98 % ; complete remission [ CR ] , 19 % ; partial remission [ PR ] , 68 % ) was achieved in 38 evaluable patients ( 81 % of intent-to-treat population ) . CLL cells were cleared from blood in 95 % patients in a median time of 21 days . CR or nodular PR in the bone marrow was achieved in 66 % of the patients and most patients achieved this after 18 weeks of treatment . An 87 % OR ( 29 % CR ) was achieved in the lymph nodes . The median time to treatment failure has not yet been reached ( 18 + months ; range , 8 - 44 + months ) . Transient injection site skin reactions were seen in 90 % of patients . Rigor , rash , nausea , dyspnea , and hypotension were rare or absent . Transient grade IV neutropenia developed in 21 % of the patients . Infections were rare , but 10 % patients developed cytomegalovirus ( CMV ) reactivation . These patients rapidly responded to intravenous ganciclovir . One patient , allergic to cotrimoxazole prophylaxis , developed Pneumocystis carinii pneumonia .  Alemtuzumab is highly effective as first-line treatment in patients with B-CLL . Prolonged treatment is important for maximal bone marrow response . Subcutaneous administration induced very few " first-dose " flulike symptoms and may reduce health care costs in comparison with the intravenous infusions Patients with CLL responding to initial chemotherapy with fludarabine alone ( F ) or in combination with cyclophosphamide ( FC ) were r and omized for treatment with alemtuzumab ( 30 mg i.v . TIW , 12 weeks ) or observation . Of 21 evaluable patients , 11 were r and omized to  alemtuzumab  before the study was stopped due to severe infections in seven of 11 patients . These infections ( one life-threatening pulmonary aspergillosis IV ; four CMV reactivations III requiring i.v . ganciclovir ; one pulmonary tuberculosis III ; one herpes zoster III ) were successfully treated and not associated with cumulative dose of alemtuzumab . In the observation arm , one herpes zoster infection II and one sinusitis I were documented . At 6 months after r and omization , two patients in the alemtuzumab arm converted to CR , while three patients in the observation arm progressed . After alemtuzumab treatment , five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive ( P=0.048 ) . At 21.4 months median follow-up , patients receiving alemtuzumab showed a significant longer progression-free survival ( no progression vs mean 24.7 months ; P=0.036 ) . In conclusion , a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL , but a safe treatment regimen needs to be determined N 1988 , THE National Cancer Institute-sponsored Working Group ( NCI-WC ) on chronic lymphocytic leukemia ( CLL ) published guidelines for the design and conduct of clinical trials in CLL with two major objectives : first , to facilitate comparisons of results of clinical trials in CLL by providing st and ardized eligibility , response , and toxicity criteria ; and , second , to encourage a framework on which to evaluate new scientific studies related to our increasing underst and ing of the biology and immunology of this disease . ' These guidelines were rapidly adopted by the majority of the clinical trials community , and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine . The differences between these guidelines and those subsequently published by the International Working Group on CLL ( IWCLL ) , which were general- practice recommendations ' are listed in Table 1 . For diagnosis , the NCI-WC requires a lymphocyte count of 5 X loy & which is lower than the 10 X 109/L required by the IWCLL , unless the lymphocytes are B cells and the bone marrow is involved . To be considered a complete remission ( CR ) , the NCI-WC criteria specify that less than 30 % lymphocytes must be present in the bone marrow , with a recommendation that the clinical significance of lymphoid nodules be assessed prospect ively ( Table 1 ) ; the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR . The IWCLL uses a shift in clinical stage as the sole index of partial remission ( PR ) , whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift . The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy , hematologic toxicity , and other important components for clinical trials design . The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years . Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and , also , with the experience following the use of newer , more effective agents , such as fludarabine . " ' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group , it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version This study investigated the efficacy , safety , and clinical benefit of alemtuzumab ( Campath-1H ) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy . Ninety-three patients received alemtuzumab in 21 centers worldwide , with the aim to obtain an overall response rate of at least 20 % . Dosage was increased gradually ( target 30 mg , 3 times weekly , for a maximum of 12 weeks ) . Infection prophylaxis was m and atory , beginning on day 8 , and continuing for a minimum of 2 months after treatment . Responses were assessed at weeks 4 , 8 , and 12 , and patients were followed for 34 months . Overall objective response in the intent-to-treat population ( n = 93 ) was 33 % ( CR 2 % , PR 31 % ) . Median time to response was 1.5 months ( range , 0.4 - 3.7 months ) . Median time to progression was 4.7 months overall , 9.5 months for responders . At data cut-off , 27 patients ( 29 % ) were alive ; overall median survival was 16 months ( 95 % CI : 11.8 - 21.9 ) and 32 months for responders . Nineteen responders survived more than 21 months . Clinical benefit was observed both in responders and in patients with stable disease . The most common adverse events were related to infusion , generally grade 1 or 2 in severity , occurring mainly in the first week . Grade 3 or 4 infections were reported in 25 patients ( 26.9 % ) . However , only 3 ( 9.7 % ) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study . Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group BACKGROUND Fludarabine seems to be a promising treatment for patients with advanced chronic lymphocytic leukaemia ( CLL ) . We compared fludarabine therapy with the combination of cyclophosphamide , doxorubicin , and prednisone ( CAP ) for treatment of CLL in a r and omised , multicentre prospect i ve trial . METHODS Patients older than 18 years of age were entered into the study if they presented with previously untreated B-cell lineage CLL ( B-CLL ) of Binet stages B or C or relapsed B-CLL pretreated with chorambucil or similar non-anthracycline-containing regimens .  Patients were r and omly assigned to either fludarabine ( 25 mg/m2 per day on days 1 - 5 ) or CAP ( cyclophosphamide 750 mg/m2 per day and doxorubicin 50 mg/m2 per day on day 1 , and prednisone 40 mg/m2 per day on days 1 - 5 ) , both given for six courses . FINDINGS Of 196 evaluable patients , 100 were previously untreated whereas 96 patients had received prior therapy .  Remission rates were significantly higher after fludarabine than CAP , with overall response rates of 60 % and 44 % , respectively ( p = 0.023 ) . A higher response rate to fludarabine was observed in both untreated ( 71 % vs 60 % , p = 0.26 ) and pretreated ( 48 % vs 27 % , p = 0.036 ) cases , although the difference was statistically significant only in pretreated cases . In the latter group , remission duration and survival did not differ between treatment groups with a median remission duration of 324 days after fludarabine and 179 days after CAP ( p = 0.22 ) and median survival times of 728 days and 731 days , respectively . In untreated cases , on the other h and , fludarabine induced significantly longer remissions than CAP with the median not yet reached after fludarabine and a median of 208 days after CAP ( p < 0.001 ) . This effect also translated into a tendency towards longer overall survival after fludarabine ( p = 0.087 ) . Treatment-associated side-effects consisted in both regimens of predominantly myelosuppression and in particular granulocytopenia . CAP-treated patients had a higher frequency and severity of nausea and vomiting ( 25 % vs 5 % , p < 0.001 ) and alopecia ( 65 % vs 2 % , p < 0.001 ) . INTERPRETATION Fludarabine provided an effective and well-tolerated therapy for patients with advanced CLL , which compared favourably with CAP as one of the most effective st and ard regimens . In second-line therapy , fludarabine induced a significantly higher rate of complete and partial remissions , while in first-line therapy a significant prolongation of remission was obtained , which may translate into an improvement of overall survival PURPOSE To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab ( FluCam ) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia ( B-CLL ) . PATIENTS AND METHODS A total of 36 patients were treated in this phase II study ( median age , 61.47 years ; mean number of prior chemotherapies , 2.6 ; Binet stage C , n = 28 ) . After an initial dose escalation of alemtuzumab over 3 days , alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days . Treatment was repeated after 28 days for up to six cycles . Restaging ( following National Cancer Institute criteria ) was carried out after cycles 2 and 4 and 1 month after the end of treatment . RESULTS The overall response rate was 83 % ( 11 complete responses , 19 partial responses , one stable disease , and five progressive diseases ) . Two patients with progressive disease developed fungal pneumonias , and one patient died as a result of Escherichia coli sepsis . Two sub clinical cytomegalovirus reactivations occurred . CONCLUSION The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL PURPOSE This phase II pilot study determined the efficacy and safety of alemtuzumab ( Campath-1H ; Burroughs Wellcome , United Kingdom ) in patients with chronic lymphocytic leukemia ( CLL ) , all of whom had previously received fludarabine and other chemotherapy regimens . PATIENTS AND METHODS Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States . The target dose of 30 mg over 2 hours , three times weekly , was administered for up to 16 weeks . Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria . Safety assessment s included analysis of lymphocyte sub population s. Antimicrobial prophylaxis was not m and atory . RESULTS Eight patients ( 33 % ) achieved a major response ( all partial remissions ) , with a median time to response of 3.9 months ( range , 1.6 to 5.3 months ) . The median duration of response was 15.4 months ( range , 4.6 to > or= 38.0 months ) , the median time to disease progression was 19.6 months ( range , 7.7 to > or= 42.0 months ) , and the median survival time was 35.8 months ( range , 8.8 to > or= 47.1 months ) . Acute infusion-related events , mainly grade s 1 and 2 , were most common and most severe in the first week 
    Output:
    
Treatment with alemtuzumab is a reasonable option for patients  with progressive and symptomatic cll that is refractory to both alkylator-based and fludarabine-based regimens .
Treatment with alemtuzumab is associated with significant and potentially serious treatment-related toxicities .
Given the potential toxicities associated with alemtuzumab , and given the limited nature of the agent 's testing in clinical trials in broad population s of patients with cll , the use of alemtuzumab in patients with important comorbidities may be associated with excessive risks