***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: After more than three decades of clinical trials testing various st and ard-dose chemotherapy regimens , the disease course of patients with multiple myeloma has not changed appreciably . Conventional chemotherapy can provide effective palliation but is not curative ( 1 ) . Case series have described encouraging results in patients with myeloma undergoing allogeneic or autologous bone marrow or peripheral blood stem-cell transplantation ( 2 ) . Other studies of transplantation , including r and omized trials , have been reported in the past 6 years ( 3 , 4 ) . To facilitate decisions about treatment options , practice guidelines have been developed for use by health care providers and consumers . In Ontario , Canada , cancer treatments and policies are led by a state-funded organization , Cancer Care Ontario . To help derive treatment options , Cancer Care Ontario has developed the Program in Evidence -Based Care , which includes the Practice Guidelines Initiative . Disease Site Groups ( DSGs ) , which comprise physicians , epidemiologists , and consumers , develop guidelines through a systematic process that involves assessment of evidence , consensus , and a validation process involving practitioners from across the province . Guideline topics are chosen through a prioritization process that includes the burden of illness , availability of evidence , perceived variation in practice , the potential to affect treatment decisions , and re source utilization . The Hematology DSG noted that the use of transplantation for patients with myeloma varied among practice s across the province . Variability in practice and emerging evidence of higher quality made this a priority topic for guideline development . To approach this topic , the DSG addressed the following questions : What is optimal st and ard-dose chemotherapy for patients with myeloma ? In terms of survival , is  peripheral blood stem-cell  or  marrow transplantation better than conventional chemotherapy ? What is the relative efficacy of autologous versus allogeneic transplantation ? What specifics of the transplantation process can be recommended ? When should transplantation be performed ? Who should ( or should not ) receive a transplant ? Methods Overview of Guideline Development This guideline was developed by the Cancer Care Ontario Practice Guidelines Initiative ( CCOPGI ) using the methods of the Practice Guidelines Development Cycle ( 5 ) . Members of the CCOPGI 's Hematology DSG selected , review ed , and interpreted the evidence . This DSG comprises 25 members , including hematologists , medical and radiation oncologists , an epidemiologist , and 2 lay representatives . Several of the physician members have background training in epidemiology ; 8 hematologists regularly perform stem-cell transplantation in clinical practice . The DSG 's draft recommendations were circulated through a mailed survey to hematologists and medical or radiation oncologists in Ontario for feedback and involvement in a consensus process . Responses were used to guide the reformatting of the draft into the final guideline recommendations . The Practice Guidelines Co-ordinating Committee ( PGCC ) , which ensures consistency of guideline development across the DSGs of various tumor sites , approved the guideline . The CCOPGI has a st and ardized process to up date each guideline report ; the current guideline was up date d and review ed by the PGCC in October 2000 . Literature Search Strategy We search ed the MEDLINE , CANCERLIT , and Cochrane Library data bases for literature published from 1992 to December 1997 and subsequently up date d the search in October 1998 , June 1999 , and April 2000 . For the search es , we combined multiple myeloma ( as a Medical Subject Heading [ MeSH ] and text word ) with bone marrow transplantation ( MeSH and text word ) and drug therapy ( MeSH ) . Then , we combined these terms with the search terms for the following study design s : practice guidelines ; systematic review s or meta-analyses ; review s ; r and omized , controlled trials ; controlled clinical trials ; and comparative studies . In addition , we search ed the PubMed and Physician Data Query ( PDQ ) ( www.cancer.gov/ search / clinical _ trials/ ) data bases and review ed relevant conference proceedings ( American Society of Hematology , 1997 to 1999 , and American Society of Clinical Oncology , 1999 to 2000 ) , article bibliographies , and personal files . To address the issue of optimal chemotherapy , we performed an additional search of the same data bases using the term multiple myeloma ( MeSH ) combined with r and omized , controlled trials ( MeSH ) and the text word r and om in the title . Inclusion Criteria We selected study reports meeting one of the three following criteria : r and omized trial or meta- analysis of therapy for patients with myeloma that reported survival or quality -of-life outcomes ; nonr and omized comparative trial that addressed transplantation strategy , including a contemporaneous control group , and that reported survival or quality -of-life outcomes ; or economic evaluation that addressed transplantation strategy . Because of insufficient data on the specifics of the transplantation process and the patients who would be most likely to benefit from transplantation , we performed a second search , which identified data from noncomparative case-series studies . Data Extraction and Interpretative Summary Three members of the DSG , including an epidemiologist , determined eligibility of the articles and abstract s obtained from the literature search . The lead DSG member for this guideline extracted and summarized relevant data according to the guideline question addressed . The DSG members then review ed the summarized data and key articles . The DSG met formally three to four times annually ; at these meetings , the members method ologically assessed the articles , interpreted the data , and debated specific points in an attempt to reach a consensus . Synthesizing the Evidence Because all of the nine r and omized trials on transplantation addressed different questions , we did not statistically pool the data . DSG Consensus Process Through an iterative process that included debate at formal meetings and circulation of draft recommendations , we considered the implication s of the appraised data for each guideline question . With this process , attempts were made to reach consensus ; when this was impossible , minority opinions were recorded . Approval by each member of the DSG was required before circulation of the draft version for practitioner feedback and su bmi ssion of the final guideline to the PGCC . Practitioner Feedback To obtain practitioner feedback , we mailed a survey to 211 practitioners in Ontario ( 94 hematologists , 93 medical oncologists , and 24 radiation oncologists ) . The survey consisted of st and ardized items asking the practitioner to rate the quality of each draft guideline and to judge whether the draft recommendations should serve as a practice guideline . Written comments were invited . Follow-up reminders were sent at 2 weeks ( by postcard ) and 4 weeks ( entire package ) . After exclusion of 18 retired practitioners , 137 of 193 practitioners ( 71 % ) responded ; 90 of 137 respondents ( 66 % ) indicated that the guideline was relevant to their practice . Approval of the draft guideline was strong among these 90 practitioners : 91 % agreed or strongly agreed that the summary of the evidence was acceptable , 87 % agreed with the draft recommendations , and 81 % approved of the recommendations as a practice guideline . Thirty-nine respondents provided written comments ; these comments were , like the other responses , incorporated in the final guideline . Results Sixty-six reports met the criteria for inclusion and are categorized in Table 1 . In each section below , we describe the studies , summarize results , and describe the guideline development . Table 1 . Evidence Included in This Practice Guideline Report What Is Optimal St and ard-Dose Chemotherapy  for Patients with Multiple Myeloma ? To properly compare transplantation with conventional chemotherapy , we must define optimal conventional chemotherapy . We identified 30 r and omized trials comparing therapies in previously untreated patients . Four meta-analyses ( 6 - 9 ) evaluated these data . The Myeloma Trialists ' Collaborative Group ( 7 ) compared combination chemotherapy with melphalan plus prednisone in a meta- analysis of 27 trials . Twenty of these trials supplied individual-patient data . No difference in survival was detected . The proportional reduction in the annual odds of death was 1.5 % in favor of combination chemotherapy ( 95 % CI , 8 % to 5 % ; P > 0.2 ) , with an odds ratio ( OR ) of 0.99 ( CI , 0.93 to 1.05 ) . An earlier literature -based meta- analysis ( 6 ) of 18 trials also failed to detect a survival difference between groups ( OR , 1.04 [ CI , 0.90 to 1.19 ] ; P > 0.2 ) . Two meta-analyses evaluated interferon for multiple myeloma . An overview of 24 r and omized trials published in abstract form ( 8) demonstrated that interferon improved recurrence-free survival by 6 months and improved 3-year overall survival by 4 % . Another meta- analysis ( 9 ) measured survival by a unique measure called the mean lifetime survival . This meta- analysis found no difference in survival rate between the group receiving interferon and the group not receiving interferon ( 3.9 vs. 3.4 years , respectively ; P = 0.095 ) . Guideline Recommendation Multiagent chemotherapy or melphalan plus prednisone is appropriate therapy for a control group in a comparison of transplantation versus st and ard-dose therapy . The addition of interferon is unlikely to influence outcomes in the control group . In Terms of Survival , Is Autologous Peripheral Blood Stem-Cell or Bone Marrow Transplantation Better than Conventional Chemotherapy ? We review ed two r and omized and three nonr and omized comparisons ( Table 2 ) . Attal and colleagues ( 3 ) r and omly assigned 200 previously untreated patients younger than 65 years of age with stage II or III ( 40 ) myeloma to conventional chemotherapy or to a strategy that included autologous bone marrow transplantation . Patients were r and omly This report of a phase 2 trial of thalidomide ( THAL ) ( 200 mg/d ; 200 mg increment every 2 weeks to 800 mg ) for 169 patients with advanced myeloma ( MM ) ( abnormal cytogenetics ( CG ) , 67 % ; prior autotransplant , 76 % ) extends earlier results in 84 patients . A 25 % myeloma protein reduction was obtained in 37 % of patients ( 50 % reduction in 30 % of patients ; near-complete or complete remission in 14 % ) and was more frequent with low plasma cell labeling index ( PCLI ) ( below 0.5 % ) and normal CG . Two-year event-free and overall survival rates were 20 % + /- 6 % and 48 % + /- 6 % , respectively , and these were superior with normal CG , PCLI of less than 0.5 % , and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months ( median cumulative dose ) ( l and mark analysis ) ; this supports a THAL dose-response effect in advanced MM BACKGROUND This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies . METHODS We r and omly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib ( 1.3 mg per square meter of body-surface area ) on days 1 , 4 , 8 , and 11 for eight three-week cycles , followed by treatment on days 1 , 8 , 15 , and 22 for three five-week cycles , or high-dose dexamethasone ( 40 mg orally ) on days 1 through 4 , 9 through 12 , and 17 through 20 for four five-week cycles , followed by treatment on days 1 through 4 for five four-week cycles . Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression . RESULTS Patients treated with bortezomib had higher response rates , a longer time to progression ( the primary end point ) , and a longer survival than patients treated with dexamethasone . The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone ( P<0.001 ) , and the complete response rates were 6 percent and less than 1 percent , respectively ( P<0.001 ) . Median times to progression in the bortezomib and dexamethasone groups were 6.22 months ( 189 days ) and 3.49 months ( 106 days ) , respectively ( hazard ratio , 0.55 ; P<0.001 ) . The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone ( P=0.003 ) , and the hazard ratio for overall survival with bortezomib was 0.57 ( P=0.001 ) . Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone . CONCLUSIONS Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies PURPOSE To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma ( MCL ) . PATIENTS AND METHODS Patients with indolent and MCL were eligible .  Bortezomib was given at a dose of 1.5 mg/m2 on days 1 , 4 , 8 , and 11 . Patients were required 
    Output:
    
Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment ; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation .
Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation .