***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: Previous phase I-II clinical trials have shown that recombinant human erythropoietin ( rHuEpo ) can ameliorate anemia in a portion of patients with multiple myeloma ( MM ) and non-Hodgkin 's lymphoma ( NHL ) . Therefore , we performed a r and omized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo .  A total of 146 patients who had hemoglobin ( Hb ) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial . Patients were r and omized to receive 1,000 U ( n = 31 ) , 2,000 U ( n = 29 ) , 5,000 U ( n = 31 ) , or 10,000 U ( n = 26 ) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy ( n = 29 ) . Of the patients , 84 suffered from MM and 62 from low- to intermediate- grade NHL , including chronic lymphocytic leukemia ; 116 of 146 ( 79 % ) received chemotherapy during the study . The mean baseline Hb level was 9.4 + /- 1.0 g/dL. The median serum Epo level was 32 mU/mL , and endogenous Epo production was found to be defective in 77 % of the patients , as judged by a value for the ratio of observed-to-predicted serum Epo levels ( O/P ratio ) of < or = 0.9 . An intention-to-treat analysis was performed to evaluate treatment efficacy . The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 ( P = .57 ) , 0.22 ( P = .05 ) , 0.43 ( P = .01 ) , and 0.58 ( P = .0001 ) g/dL in the 1,000 U , 2,000 U , 5,000 U , and 10,000 U groups , respectively ( P values versus control ) . The probability of response ( delta Hb > or = 2 g/dL ) increased steadily and , after 8 weeks , reached 31 % ( 2,000 U ) , 61 % ( 5,000 U ) , and 62 % ( 10,000 U ) , respectively . Regression analysis using Cox 's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo , whereas only one quarter of those with adequate Epo levels did so . Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50 % of these patients are expected to respond to rHuEpo . Thus , rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production . From a practical point of view , we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels , whereas the choice of the initial dosage should be based on residual marrow function PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL Nine B‐chronic lymphocytic leukaemia ( B‐CLL ) patients suffering from anaemia , due to no obvious cause except their disease , were treated with recombinant human erythropoietin ( r‐HuEPO ) . The treatment protocol provided a closed label phase of 3 months duration , during which the patients received r‐HuEPO or placebo in a ratio of 2:1 , followed by an open label phase , also of 3 months duration , during which r‐HuEPO was administered to all patients three times a week s.c . r‐HuEPO was given at a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a maximum of 300 U/kg three times a week . Complete response was achieved in 5/9 ( 55 % ) patients and partial response in 3/9 ( 33 % ) . The response obtained was independent of the pretreatment serum EPO levels , the duration of anaemia , the concomitant administration of chemotherapy , the presence of splenomegaly , or the degree of bone marrow infiltration by lymphocytes . It appears that r‐HuEPO is very effective in reversing the disease‐related anaemia of B‐CLL patients PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer OBJECTIVE To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy , we conducted a multicenter , r and omized , double-blind trial . METHODS A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum , taxanes or anthracyclines were enrolled in the study . Patients were r and omly assigned into groups that received three dose levels of epoetin-beta ( 9000 , 18,000 or 36,000 IU ) administered subcutaneously once a week for 12 weeks . The primary endpoint was change in hemoglobin , while the secondary endpoints were quality of life ( QOL ) assessed by Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire and transfusion requirements . RESULTS Among the 69 patients ( per protocol set population ) assessable for efficacy , hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group ( 1.75 + /- 2.15 versus 0.04 + /- 1.98 g/dl ; P = 0.009 ) , and a significant dose-response relationship was observed for the change in hemoglobin level ( P = 0.003 ) . Although changes in FACT-An Total Fatigue subscale ( Fatigue subscale ) scores were similar for the three dosage groups , there was a statistically significant correlation ( r = 0.435 , P < 0.001 ) between the change in hemoglobin levels and the change in Fatigue subscale scores . The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group ( P = 0.022 , not adjusted for pre- study transfusions ) . The incidence of adverse events was similar in the three dosage groups . CONCLUSIONS Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy BACKGROUND Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life ( HRQOL ) . We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL . PATIENTS AND METHODS These analyses were based on five r and omized trials . Patients completed the Functional Assessment of Cancer Therapy ( FACT ) Anemia scales and numeric rating scales of Energy , Activity and Overall Health  at baseline and after the 12-week treatment period . t-tests and linear regression models were used to evaluate associations . Analyses were stratified into three groups : solid tumor chemotherapy patients , lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients . RESULTS Adjusted mean differences ( 95 % CI ) in FACT Fatigue change scores between hemoglobin responders ( > or = 2 g/dl increase ) and non-responders were 3.0 ( 1.2 , 4.7 ) , 2.8 ( 0.6 , 5.0 ) and 5.8 ( 2.2 , 9.5 ) among the solid tumor , lymphoproliferative malignancy and non-chemotherapy groups , respectively . Significantly greater improvements ( P < 0.01 ) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue ( FACT Fatigue change score > or =3 points ) . After controlling for other factors , patients whose fatigue improved reported substantially greater improvements in energy , ability to perform usual activities and overall health ( P < 0.0001 ) . CONCLUSIONS Across five trials of cancer patients on and off chemotherapy , hemoglobin response was associated with meaningful improvements in fatigue , which , in turn , was associated with improved physical , functional , emotional and overall well-being Anemia is a frequent complication of multiple myeloma , becoming chronic in patients who are resistant to chemotherapy . This r and omized , parallel , controlled multicenter study ( 71 patients receiving concomitant chemotherapy ) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy . Forty patients were treated with subcutaneous epoetin alfa ( 150 IU/kg per dose , increasing to 300 IU/kg per dose , every 3 weeks ) for 6 months , and 31 entered a control group . The epoetin alfa group had a significantly ( P≤0.001 ) greater percentage of patients ( 75 % vs. 21 % ) with increases in hemoglobin levels and /or reduced transfusion requirements . In 44 non pre-transfused patients ( 20 controls , 24 in the epoetin alfa group ) , the mean increase in hemoglobin was significantly ( P≤0.0001 ) greater in the epoetin alfa group ( + 2.1 vs. −0.2 g/dl ) . Increases in hematocrit and red blood cells were also significantly ( P≤0.0001 ) greater in epoetin alfa-tre 
    Output:
    
We conclude that available data evaluating ESAs in patients with hematologic malignancies demonstrate that these agents reduce transfusion requirements .
Limitations of these data preclude conclusions that these agents improve QOL .