Hb Decline Research Articles

Erythropoiesis-stimulating agents in cancer patients: ESMO Recommendations for use

Erythropoiesis-stimulating agents in cancer patients: ESMO Recommendations for use

Correlation Between Hemoglobin and Fatigue in Women Undergoing Adjuvant Chemotherapy Without Erythropoietin-Stimulating–Agent Support

Background Fatigue is a common complication of adjuvant chemotherapy and compromises the quality of life of breast cancer survivors. We sought to correlate serial hemoglobin (Hb) levels with fatigue in a population of women on adjuvant chemotherapy, none of whom received erythropoietin-stimulating agents or red blood cell transfusions. Patients and Methods Seventy-five women participated in a study using quality-of-life questionnaires to assess changes in need for psychosocial support over time. Questionnaires were administered within 30 days of initiating adjuvant therapy and at 2, 6, and 12 months. Fatigue was assessed by the 36-Item Short-Form Health Survey (SF-36). Hemoglobin levels at each time point were captured retrospectively. Complete data are included for 40 of the 46 women who received adjuvant chemotherapy. Paired-samples t tests were conducted to compare mean SF-36 Energy/Fatigue scores between time points, and independent-samples t tests were conducted for comparisons against norms. Simple correlations (Pearson R) were conducted between SF-36 variables and Hb levels at each time point. Results At 2 months, 23.4% of women had Hb < 11 g/dL compared with 12.9% at 12 months. Compared with norms for women in the general population and breast cancer survivors, these women reported worse fatigue at baseline and at 2 and 6 months. A strong linear relationship was observed between Hb at 2 months and SF-36 Energy/Fatigue scores at 12 months ( r = 0.71; P = .002). Conclusion Participants with high fatigue at 12 months had Hb levels at 2 months 13% lower than those with low fatigue. This finding suggests that chemotherapy-induced decline in Hb might be a marker of physiologic reserve.

Blood transfusion requirements and independent predictors of increased transfusion requirements among adult patients on extracorporeal membrane oxygenation – a single centre experience

More adults undergo extracorporeal membrane oxygenation (ECMO) now. They have high transfusion requirements. This study described transfusion requirements of adults during ECMO in a single institution, and determined factors associated with high transfusion requirements. Retrospective analysis was done on the amount of blood products received by adults during ECMO. Predictors of increased average daily transfusion requirements during ECMO and increased ECMO duration (which correlated positively with total transfusion requirements) were determined. Forty-one patients (median age 50 years) underwent 42 ECMO sessions for respiratory failure (16.7%), cardiogenic shock (76.2%) or massive pulmonary embolism (7.1%). They received 569 red blood cells, 852 platelets, 126 fresh-frozen plasma (FFP) and 220 cryoprecipitate in total during median ECMO duration of 5 (1-15) days. On multivariate analysis, average daily red blood cell transfusion increased with nadir haemoglobin (Hb) during ECMO (Hb(nadir)) of < 7.5 g/dl (P < 0.001). Average daily platelet transfusion increased with recent antiplatelet agents (P = 0.015) and maximum Hb decline of > 5.5 g/dl during ECMO (P = 0.011). Average daily platelet transfusion > 3 units was also associated with increased ECMO duration (P = 0.024). Average daily FFP transfusion was increased in patients with hypertension (P = 0.007) and Hb(nadir) < 7.5 g/dl (P = 0.050). Patients with sepsis (P = 0.009) or without surgery (P = 0.009) had increased ECMO duration, which correlated positively with total transfusion requirements during the entire ECMO session. ECMO improved mortality of patients with fulminant myocarditis, respiratory failure and massive pulmonary embolism. Adult ECMO patients with lower Hb(nadir) require more daily red blood cell and FFP. Hypertension increases daily FFP requirements. Recent antiplatelet agents, larger Hb decline and longer ECMO duration increase daily platelet requirements. Patients with sepsis or on ECMO for medical reasons have longer ECMO duration, which is associated with total transfusion requirements. Some of these factors may be identified early to optimize blood product support.

Assessing adherence to the European Organization for Research and Treatment of Cancer (EORTC) guidelines for the use of erythropoiesis-stimulating agents in cancer patients

20696 Background: Anemia is a common symptom in cancer patients and has a considerable impact on patient quality of life (QoL). According to the European Cancer Anemia Survey, anemia was treated in only 38.9% of patients. Erythropoiesis-stimulating agents (ESAs) are widely used for the treatment of the chemotherapy-induced anemia (CIA). The European Organization for Research and Treatment of Cancer (EORTC) recently published guidelines for the use of ESAs in cancer patients, but actual adherence to these guidelines in clinical practice is unknown. Methods: Between March and July 2007, 16 working sessions were held and 179 Spanish oncologists were consulted to assess their adherence to the EORTC guidelines (update 2006)for the use of ESAs. In all sessions, a preliminary presentation about these guidelines was given, followed by a structured discussion that was facilitated by a moderator using an organized, brain storming work method (Metaplan). Results: Over 90% of oncologists agreed that the two major goals of ESA therapy are improvement of QoL and prevention of transfusions; 70% consider that CIA treatment with ESA should be initiated at a hemoglobin (Hb) level of 10–11g/dL. ESAs are administered every week (59%) or every three weeks (33%). In the opinion of 64% of respondents, the target Hb concentration should be 12–13 g/dL. Altogether 45% of oncologists use ESA in anemic patients with an Hb level of <11.9 g/dL to prevent a further decline in Hb. All participants agreed with the use of fixed doses of ESAs. Intravenous iron supplementation is low (5%). Conclusions: These study results show good adherence to the current EORTC guidelines in Spain, but action to increase adherence may improve patient outcomes. The main discrepancies are the use of intravenous iron and ESA in patients with Hb <11.9 g/dL. This study was supported by Amgen S.A. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen

Short‐term ferrous sulfate supplementation in female blood donors

Iron deficiency is a public problem in women, which contributes to the high percentage of deferred blood donations in this group. This study evaluated the effect of iron supplementation in improving iron stores to promote safe blood donation in women. A total of 412 female blood donors were randomly recruited for the study. The volunteers were scheduled for an initial visit and three subsequent visits at 4-month intervals for possible repeat donation. Each volunteer was given 21 tablets of 150 mg of ferrous sulfate or placebo to be taken three times daily for 1 week after each blood donation. Their hemoglobin (Hb) concentration, hematocrit (Hct), serum ferritin, total iron-binding capacity (TIBC), and percent saturation of the TIBC were tested throughout the course of the study. The group taking ferrous sulfate showed no significant difference between the mean initial and final result for any of the values other than Hb values, whereas there was a significant decline in mean Hb, Hct, serum iron, serum ferritin, and percent saturation in the group taking placebo. Hb concentrations declined significantly in both groups; however, it was more severe in the placebo group when compared to the ferrous sulfate group. The relative risk of iron deficiency in placebo group was 3.6 (95% confidence interval = 1.73-7.74). The results indicate that supplementation therapy can be considered as one of the strategies to promote safe blood donation in women. A quantity of 150 mg of elemental iron per day as ferrous sulfate, however, is not the correct dose for Iranian female donors.

Early decline of hemoglobin can predict progression of hemolytic anemia during pegylated interferon and ribavirin combination therapy in patients with chronic hepatitis C

Ribavirin, used to treat chronic hepatitis C, can induce hemolytic anemia, forcing the discontinuance of treatment. To establish a predictive measure to help circumvent this, we evaluated the relationship of hemoglobin (Hb) decline with the discontinuance of treatment during the progression of ribavirin-induced anemia. One hundred and sixteen patients (71% male) with genotype 1 chronic hepatitis C were treated with pegylated interferon (PegIFN) alpha-2b and ribavirin. The mean age was 50.6 years and 55% were IFN naïve. A decline of Hb concentration by 2 g/dL at two weeks from the start of the treatment ("2 by 2" standard) was adopted as the predictive factor for the progression of anemia. By applying the "2 by 2" standard, with DeltaHb >/= 2 g/dL (34%, n = 39), treatment was discontinued in 12 cases (31%), three of which (8%) because of severe anemia. ForDeltaHb < 2 g/dL (64%, n = 76), treatment was discontinued in 11 (14%) cases; none due to severe anemia. Ten percent (4/39) of patients showed the minimum Hb </= 8.5 g/dL in the DeltaHb >/= 2 g/dL group, with none in the DeltaHb < 2 g/dL group (P = 0.001). Furthermore, the patients with minimum Hb </= 8.5 g/dL were found only in the "2 by 2" standard-positive and low CL/F (<15) group (4/29, 14%). Monitoring the Hb decline using the "2 by 2" standard can identify patients who are prone to developing severe anemia. Further prospective studies are needed using ribavirin reduction based on the "2 by 2" standard.

Randomized trial on the therapeutic equivalence between Eprex and GerEPO in patients on haemodialysis

Treatment of renal anaemia with epoetin is well established. However, epoetin is expensive. Biogeneric epoetin with proven efficacy would reduce cost and improve access to therapy. We conducted this first ever comparative study of a biogeneric and the original product. Stable haemodialysis patients with haemoglobin (Hb) of at least 9 g/dL and receiving the human recombinant erythropoietin Eprex were randomized to continue Eprex or convert to GerEPO, a biogeneric epoetin, for 12 weeks. The primary efficacy variable was a change in Hb from baseline. Ninety-three subjects were randomized to each arm. Ninety-two and 87 subjects on the Eprex and GerEPO arms, respectively, completed the trial. Mean Hb in both groups declined over time. The mean decline in Hb was -0.47 g/dL in the Eprex group and -0.45 g/dL in the GerEPO group. The mean difference in the change in Hb from baseline to week 12 between the two groups was 0.02. The 95% confidence interval was -0.42 to 0.46, which lies within the margin of equivalence (+/-0.5 g/dL). The results of intention-to-treat analysis were similar. There were no significant differences in the epoetin dose, iron therapy or iron stores between the groups. Patients receiving GerEPO reported more adverse events. GerEPO was therapeutically equivalent to Eprex with respect to Hb response for patients with Hb in the subtherapeutic target range as is common in this study population. The trial duration was insufficient for safety evaluation, which must await further investigation. More biogeneric products should be subjected to rigorous evaluation.

A Prospective Randomized Study Comparing Monopolar and Bipolar Transurethral Resection of Prostate Using Transurethral Resection in Saline (TURIS) System

ObjectivesTo compare transurethral resection of prostate (TURP) using monopolar and bipolar transurethral resection in saline (TURIS) system. Materials and methodsA prospectively randomized study was conducted between January 2004 and January 2005. Patient demographics and indications for surgery were recorded. The safety end points studied were occurrence of complications and decline in postoperative serum sodium (Na+) and hemoglobin (Hb) levels. Efficacy end points were resection time, weight of resected prostate tissue, and improvement in International Prostate Symptoms Score (IPSS) and maximum flow rate (Qmax) in patients’ uroflow over 12 mo. ResultsOne hundred consecutive patients were randomized and completed the study, with 52 patients in the monopolar TURP group and 48 in the TURIS group. At baseline, the two groups were comparable; they had at least 12 mo of follow-up.Mean resection time and mean weight of resected prostate tissue were comparable for both groups. Declines in the mean postoperative serum Na+ for TURIS and monopolar TURP groups were 3.2 and 10.7mmol/l, respectively (p<0.01). However, there was no statistical difference in the decline in postoperative Hb between the two groups.There were two cases of clinically significant transurethral resection syndrome in the monopolar group. Urethral strictures were observed in three cases of TURIS and one patient in the monopolar group. The IPSS and Qmax improvements were comparable between the two groups at 12 mo of follow-up. ConclusionsBipolar TURP using the TURIS system is clinically comparable to monopolar TURP at 1 yr with an improved safety profile.

Ischemic Vasoconstriction And Tissue Energy Metabolism during Global Cerebral Ischemia in Gerbils

Vasoconstriction is known to occur in cerebral arterioles during ischemia and considered to be distinct from vasospasm seen after subarachnoid hemorrhage. To elucidate the mechanism and functional significance underlying ischemic vasoconstriction, we investigated the relationship between arteriolar constriction and tissue energy metabolism during bilateral common carotid artery occlusion in gerbils. Using video microscopy and microspectroscopy, the arteriolar caliber, the total hemoglobin (Hb) content, and the redox state of cytochrome oxidase (cyt.aa3) were monitored in the cerebral cortex in vivo. After in situ freezing of the brain, adenine nucleotides, creatine phosphate (P-Cr), and lactate levels were analyzed using high-performance liquid chromatography in vitro. Tissue damage was also assessed immunohistochemically using antibodies against microtubule-associated proteins. There was a slight reduction of the diameter of pial arterioles during the initial 1 min of ischemia. A rapid decline of total Hb and reduction of cyt.aa3 were observed with rapid decreases of P-Cr and ATP in the cortical tissue during the initial 0.5 min, but all of them showed tendencies to return toward preischemic levels at 0.5-1 min. Beyond 1.5 min, extensive vasoconstriction occurred together with further decline of total Hb, reduction of cyt.aa3, and decreases of ATP and P-Cr. Neuronal damage developed in the cerebral cortex immunohistochemically beyond 3 min. The present investigation demonstrated two phases of vasoconstriction with the possibilities that the immediate vasoconstriction likely contributed to transient improvement of cortical oxygen/energy metabolism, and the second extensive vasoconstriction was an index of tissue energy failure and imminent neuronal damage.

Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C

The aim of this study was to examine the factors correlated with the progression of ribavirin-induced hemolytic anemia in patients with chronic hepatitis C treated by interferon and ribavirin combination therapy. This study was conducted on 505 patients by the Osaka Liver Disease Study Group. A decline of hemoglobin (Hb) concentration by 2 g/dl at the end of 2 weeks from the start of the treatment ("2 by 2" standard) was adopted as a predictive factor for progression to severe anemia. The ribavirin apparent clearance (CL/F) was also examined. Of 482 patients whose Hb value was more than 12 g/dl before the treatment, 68 patients (14%) had to discontinue ribavirin owing to severe anemia. Patients in the "2 by 2"-positive group (Hb decline over 2 g/dl) and the group with lower CL/F were significantly more likely to discontinue ribavirin owing to severe anemia. Discontinuation was more common among patients aged 60 years or older than for those under 60 years old (21% vs. 9%, P < 0.001). Among patients aged 60 years or older, only the "2 by 2" standard was significantly associated with the discontinuance of ribavirin owing to severe anemia in a multivariate analysis (odds ratio, 4.18; P < 0.001). The "2 by 2" standard of Hb decline can be used to identify patients likely to develop severe anemia. The early reduction of ribavirin can help prevent progression to severe anemia, thus allowing ribavirin therapy to be completed even in older patients.

Zidovudine use but not weight‐based ribavirin dosing impacts anaemia during HCV treatment in HIV‐infected persons

Anaemia during peginterferon (PEG-IFN) and ribavirin (RBV) therapy is common in human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients despite the use of lower doses of RBV than are recommended for HIV-seronegative persons. In addition, concurrent zidovudine (ZDV) may exacerbate the anaemia caused by PEG-IFN and RBV. We retrospectively analysed the incidence of anaemia, RBV dose reduction and epoetin-alpha (EPO) use among coinfected patients treated with PEG-IFN and weight-based RBV (800-1400 mg/day) who enrolled in two clinical trials and had haemoglobin (Hb) levels assessed at baseline and after 4 and/or 12 weeks of HCV treatment. Overall, 217 patients were included; pre-treatment Hb levels (mean 14.7 g/dL) were similar in all patients, including ZDV users (29% of patients). After 4 weeks of therapy, the mean Hb decline was greater among ZDV recipients (3.13 g/dL) compared with those on other anti-retroviral treatment (ART) (2.13 g/dL) or on no ART (1.47 g/dL) (P < 0.0001). RBV dose reduction and EPO use were more common in patients taking ZDV compared with those not taking ZDV (P < 0.0001). RBV dose was not associated with Hb reduction, RBV dose reduction or EPO use. Virologic response after 12 weeks of therapy and the treatment discontinuation rate did not differ by ZDV use. The use of ZDV but not weight-based RBV dosing was associated with an increased risk of anaemia, RBV dose reduction or EPO use in coinfected patients treated with PEG-IFN/RBV. However, ZDV use was not associated with higher rates of treatment discontinuation or lower early virologic response rates. HIV and hepatitis C care providers should be cognizant of these data.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir+2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

Ribavirin Levels and Haemoglobin Decline in Early Virological Responders and Non-Responders to Hepatitis C Virus Combination Therapy

Therapeutic drug monitoring of ribavirin has been claimed to predict virological response and/or haematological side effects in patients with chronic hepatitis C undergoing peginterferon/ribavirin combination treatment. In the present study, steady-state ribavirin levels were retrospectively analyzed in serum samples from patients at week 12 of combination therapy with peginterferon alpha-2a or alpha-2b and ribavirin. Patients were classified as early virological responders on the basis of undetectable HCV-RNA or HCV-RNA drop ≧2 log from baseline at week 12. The mean ribavirin level was not different between early virological responders (2.3 ± 0.1 µg/ml, n = 45) and early virological non-responders (2.0 ± 0.2 µg/ml, n = 10). There was no correlation between ribavirin levels at week 12 and early virological response. In patients with early virological response, haemoglobin (Hb) levels were found to be decreased by 18% on average from the basal values; however, in only 2 patients Hb levels declined below 100 g/l. There was a moderate negative correlation between ribavirin levels and Hb levels at week 12 (R = –0.50, p < 0.001); however, ribavirin levels did not correlate with relative or absolute decline in Hb as compared to basal levels or with ribavirin dose per kilogram body weight. In addition, a significant negative correlation between ribavirin levels and glomerular filtration rate was found (R = –0.31, p < 0.05). Based on our results, monitoring of ribavirin serum levels at week 12 of HCV combination therapy does not appear to predict early virological response or reductions in Hb levels. Further research is needed to assess their diagnostic value at other time points of peginterferon/ribavirin combination treatment and/or in patients with renal insufficiency.

The Relative Benefits of Endurance and Strength Training on the Metabolic Factors and Muscle Function of People With Type 2 Diabetes Mellitus

Cauza E, Hanusch-Enserer U, Strasser B, Ludvik B, Metz-Schimmerl S, Pacini G, Wagner O, Georg P, Prager R, Kostner K, Dunky A, Haber P. The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus. Objective To compare the effects of a 4-month strength training (ST) versus aerobic endurance training (ET) program on metabolic control, muscle strength, and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D). Design Randomized controlled trial. Setting Large public tertiary hospital. Participants Twenty-two T2D participants (11 men, 11 women; mean age ± standard error, 56.2±1.1y; diabetes duration, 8.8±3.5y) were randomized into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age, 57.9±1.4y; diabetes duration, 9.2±1.7y) into a 4-month ET program. Interventions ST (up to 6 sets per muscle group per week) and ET (with an intensity of maximal oxygen consumption of 60% and a volume beginning at 15min and advancing to a maximum of 30min 3×/wk) for 4 months. Main Outcome Measures Laboratory tests included determinations of blood glucose, glycosylated hemoglobin (Hb A 1c), insulin, and lipid assays. Results A significant decline in Hb A 1c was only observed in the ST group (8.3%±1.7% to 7.1%±0.2%, P=.001). Blood glucose (204±16mg/dL to 147±8mg/dL, P<.001) and insulin resistance (9.11±1.51 to 7.15±1.15, P=.04) improved significantly in the ST group, whereas no significant changes were observed in the ET group. Baseline levels of total cholesterol (207±8mg/dL to 184±7mg/dL, P<.001), low-density lipoprotein cholesterol (120±8mg/dL to 106±8mg/dL, P=.001), and triglyceride levels (229±25mg/dL to 150±15mg/dL, P=.001) were significantly reduced and high-density lipoprotein cholesterol (43±3mg/dL to 48±2mg/dL, P=.004) was significantly increased in the ST group; in contrast, no such changes were seen in the ET group. Conclusions ST was more effective than ET in improving glycemic control. With the added advantage of an improved lipid profile, we conclude that ST may play an important role in the treatment of T2D.

Effect of androgen suppression on hemoglobin in prostate cancer patients undergoing salvage radiotherapy plus 2-year buserelin acetate for rising PSA after surgery

To examine the effect of 2-year androgen suppression (AS) on the pattern and extent of hemoglobin (Hb) change. The basis of this report was a Phase II study evaluating a combined treatment of salvage radiotherapy plus 2-year AS for a rising prostate-specific antigen level after surgery. Patients had laboratory tests performed, including Hb and serum testosterone, and answered a quality-of-life questionnaire (European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire 30 item) at regular intervals during the AS and post-AS period. The pattern and extent of the change in Hb was analyzed in relation to the testosterone level. The clinical significance of the Hb change was evaluated with a correlation analysis between Hb and the three specific domains of the questionnaire (Global Health Status, Physical Functioning, and Fatigue). Of a total of 74 accrued patients, 69 were identified as eligible for this report. The median patient age was 70 years. The median follow-up was 38.6 months. The mean Hb was 150.7 g/L at baseline and declined with radiotherapy by 5.9 g/L. The maximal Hb drop during AS was 16.0 g/L (p <0.0001), occurring at 16 months after the initiation of AS. Hb recovery in the post-AS period was slow. The decline and recovery of the mean Hb and hematocrit followed that of testosterone. The three quality-of-life domains did not show any significant correlation with the change in Hb. Two-year AS resulted in a statistically significant drop in the mean Hb, but had no clinically apparent adverse effect. The pattern of Hb change was similar to that of testosterone change.

Erythropoietic Response to Anemia in Chronic Hepatitis C Patients Receiving Combination Pegylated Interferon/Ribavirin

In hepatitis C virus (HCV)-infected patients receiving pegylated interferon (PEG-IFN)/ribavirin (RBV) combination therapy, anemia is a well-known side effect. The purpose of this study was to describe the time course and extent of hemoglobin (Hb) changes and the erythropoietic response to PEG-IFN/RBV-induced anemia. In this multicenter, observational, 8-wk study, laboratory parameters were measured weekly for 8 wk or until early withdrawal. Primary endpoints included changes in Hb and serum erythropoietin (sEPO) from baseline to week 8; other measures were changes in reticulocytes and RBV dose. The predictive value of baseline factors for maximum Hb decline was assessed. In the 97 evaluable patients, mean Hb decreased from 14.4 +/- 1.4 g/dl (baseline) to 11.9 +/- 1.3 g/dl (week 8). Twenty-one percent of patients withdrew before week 8. The estimated erythropoietic response was lower than that seen in two historic control populations of iron deficiency anemia patients. Mean RBV dose decreased from 986 +/- 190 mg/day (baseline) to 913 +/- 228 mg/day (week 8). Fifty-seven out of 77 (74%) patients who completed the study maintained their initial prescribed RBV dose. Patients maintained on the initial dose of RBV who had a higher baseline Hb and viral load showed a trend toward larger Hb declines. Platelets and white blood cells (WBCs) also declined during the study. HCV-infected patients receiving PEG-IFN/RBV therapy have reductions in Hb, platelets, and WBCs, possibly due to bone marrow suppression. They also have diminished endogenous sEPO production for their degree of anemia.

Hemoglobin and Hematocrit Values After Saline Infusion and Tourniquet

This study attempted to contribute to standardization of blood testing in sport, and to investigate the effect of artificial dilution with saline. In 10 healthy, physically active males and 3 healthy physically active females hemoglobin (Hb), hematocrit (Ht), and % reticulocytes (%retics) were measured at different time points to look for possible fluctuations during day time, while the subjects had regular coffee breaks and lunch. In 7 of the subjects in a separate experiment 500 ml of saline were infused around 8 am and Hb, Ht, and %retics were measured before and every hour thereafter until 7 hours after infusion. In addition Ht was measured on a hematological analyzer as well as with a centrifuge. In a separate experiment the effect of tourniquet duration on Hb and Ht was studied in 9 of the subjects. The results show that Hb, Ht, and %retics are stable from 8 am to 4 pm, but that infusion of 500 ml of saline induces an acute decrease in Hb and Ht within one hour (Hb decreased from 15.2+/-0.9 g/dl to 14.5+/-1.0 g/dl, and Ht from 45.6+/-2.8 % to 44.0+/-2.5 %). The decline in Hb and Ht was maintained during the 7-hour observation period. Ht values of the same samples measured with a hematological analyzer and a centrifuge were not different. Application of the tourniquet did significantly affect Hb and Ht values only from two minutes, and thereafter Hb and Ht remained stable during the rest of the 5-minute tourniquet. With blood testing in sport these results have to be taken into consideration.

Improvements in Fatigue Are Associated with Early Treatment with Every-3-Week (Q3W) Darbepoetin alfa (DA) Treatment in Anemic Patients (pts) Receiving Chemotherapy (Ctx).

Background: We recently reported final results of a randomized, open-label, multicenter study assessing the efficacy of DA (Aranesp®) 300 mcg Q3W (Rearden et al, ASCO 2004). In this study of 201 pts, pts with grade 1 anemia were treated early with DA (n=102; early group) compared with pts treated late after developing grade 2/3 anemia (ie, hemoglobin [Hb] < 10 g/dL; n=99; observation/late intervention group [obs]). When pts were untreated in the obs group, Hb declined. DA treatment maintained Hb within the NCCN Hb target range for pts in the early group and increased Hb once administered in the obs group. The objective of this analysis was to explore the impact of declining Hb levels on pt-reported outcomes using the FACT-Fatigue (FACT-F) subscale.Methods: Pts with baseline (BL) Hb ≥10.5 and ≤12 g/dL were randomized 1:1 to either the early or obs group for up to 22 weeks. To analyze pt-reported fatigue, the FACT-F subscale was administered Q3W and at the end of treatment. The FACT-F analysis set included pts who were randomized, received study drug, and had a BL and at least 1 post-BL FACT-F score. Analyses of changes in FACT-F scores during treatment from BL were conducted; missing values were not imputed.Results: In 201 randomized and treated pts, mean BL (SD) Hb was similar for each group, 11.1 (0.7) g/dL for the early and 11.2 (0.6) g/dL for the obs groups. In the early group, mean Hb increased to near 12 g/dL in approximately 7 weeks, and due to dose-withholding rules, remained near 12 g/dL for the remainder of the study. In the obs group, Hb declined to < 10 g/dL in 65% of pts. The FACT-F analysis set included 94 pts in the early group and 86 in the obs group. Mean (SD) FACT-F scores at BL were 31.6 (11.7) for the early group and 27.7 (12.8) for the obs group. With categories of Hb change at the end of treatment, a significant trend towards greater improvements in fatigue with increasing Hb levels was observed in both groups (table). In pts in whom Hb was stabilized or improved, no decrease in fatigue scores was noted. However, when Hb declined (Hb change < 0 g/dL), a statistically significant and clinically meaningful (>3 point change in FACT-F score) increase in fatigue was observed (negative change in FACT-F score). Consistent with previous studies, pts with Hb change > 2 g/dL had clinically and statistically significant improvements in fatigue.Conclusion: In the absence of treatment, most mildly anemic cancer pts receiving ctx are at risk of developing grade 2/3 anemia within approximately 7 weeks. This decline in Hb is associated with a statistically significant and clinically meaningful increase in pt-reported fatigue. Our results indicate that DA 300 mcg Q3W may effectively ameliorate the impact of ctx on Hb levels and consequently prevent a decline in fatigue. Further, Q3W DA may provide benefits associated with less-frequent dosing.Mean (95%CL) Change in FACT-F Scores At End of Treatment By Change in Hb CategoryEarlyObsN=94N=86Categories of Hb Change< 0 g/dL−6.2 (−12.9, 0.6)−2.8 (−7.2, 1.5)n=23n=38>0 to 2 g/dL0.9 (−2.2, 4.0)1.7 (−3.9, 7.3)n=52n=32> 2 g/dL8.3 (3.3, 13.2)6.4 (0.3, 12.5)n=19n=16P -value (Jonckheere-Terpstra Trend Test)0.00030.049

Assessment of Clinical Outcomes Following Erythropoietic Intervention at a Hemoglobin Concentration above 10 g/dL: A Comprehensive Review of Recent Literature.

Current practice guidelines for the management of chemotherapy-induced anemia (CIA) recommend initiating erythropoietic intervention at hemoglobin (Hb) ≤ 10 g/dL (American Society of Hematology [ASH]/American Society of Clinical Oncology [ASCO]), or at Hb ≤ 11 g/dL (National Comprehensive Cancer Network [NCCN]). This comprehensive literature review summarizes published findings of randomized controlled trials (RCTs) that evaluated the effects of initiating erythropoietic treatment at Hb > 10 g/dL on transfusion incidence, Hb concentration, and/or patient-reported outcomes, relative to control. A search of the Medline database and conference proceedings (ASH and ASCO) from 1999 to 15 June 2004 was conducted to identify RCTs that evaluated the ability of erythropoietic agents to prevent the onset or worsening of CIA. Mantel-Haenszel weighted summary estimates of the relative risk were calculated to evaluate outcomes in patients treated with epoetin alfa compared to control patients. Using predefined selection criteria, 4 full-length papers (summarized in the table) and 5 abstracts (Chang ASCO 2003; Savonije ASCO 2004; Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004) were identified and reviewed. Epoetin alfa effectively decreased transfusion incidence and the percentage of patients with Hb decline to < 10 g/dL vs no treatment in 4 RCTs reported from 1997 onward (table). The estimated summary relative risk (95% CI) for transfusion and Hb < 10 g/dL are 0.39 (0.26–0.57; P < 0.0001) and 0.48 (0.25–0.89), respectively. These results were consistent with early results reported in 2 additional RCTs (Chang ASCO 2003; Savonije ASCO 2004), which were of similar design. The preliminary results of 3 additional RCTs that directly compared outcomes following early (Hb > 10 g/dL) and late (Hb ≤ 10 g/dL) erythropoietic intervention were presented at recent ASH and ASCO conferences (Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004). All 3 studies provided evidence of lower incidence of transfusion, higher Hb levels over time, and/or better patient-reported outcomes among patients treated early compared with those treated late. The results of the studies examined demonstrate the clinical benefits of initiating erythropoietic treatment at a Hb concentration > 10 g/dL, with respect to reducing transfusion requirements and improving Hb levels, in patients with cancer undergoing chemotherapy. Although the findings are preliminary and have yet to appear in peer-reviewed journals, the comparative RCTs of early vs late intervention point to a trend in which patients who received erythropoietic treatment early experienced better clinical outcomes overall than patients treated late.Bamias 2003Thatcher 1999ten Bokkel Huinink 1998Del Mastro 1997Hb Eligibility Criterion (g/dL)≤13≥10.5< 13≥ 12Baseline Hb (g/dL)11.5 (E)13.7 (E)12.0 (E)13.0 (E)11.5 (C)13.4 (C)11.8 (C)13.1 (C)Transfusion Incidence (%)15* (E)45* (E)4**(E)0 (E)33 (C)59 (C)39 (C)6 (C)% Patients with Hb < 10 g/dLª17*** (E)48* (E)18* (E)0*** (E)46 (C)66 (C)50 (C)52 (C)Dosing Regimen10,000 U TIW150 U/kg TIW150 U/kg TIW150 U/kg TIWNo treatment (control)No treatment (control)No treatment (control)No treatment (control)E=epoetin alfa; C=no treatment control; reported p < 0.05 (*), 0.01 (**), 0.001 (***) vs control. ªHb ≤10 g/dL in Del Mastro study

Effect of androgen suppression (AS) on hemoglobin (HB) levels in prostate cancer patients undergoing post-operative adjuvant radiotherapy (RT) and 2-year as

Anemia is one of the potential adverse effects of androgen ablation, since androgen has an erythropoietic effect. This aim of this report is to examine the extent and timing of hemoglobin decline and its recovery caused by 2-year AS in prostate cancer patients undergoing a combined treatment of post-operative RT plus 2-year AS for pathological T3 and/or positive resection margins. A prospective phase II study has been in progress to evaluate the efficacy of post-operative RT plus 2-year AS for PT3 and/or positive resection margin after radical prostatectomy. There were two subgroups: one with an undetectable post-operative PSA (<0.2ng/ml) and the other with persistently detectable post-operative PSA at >3months after surgery. All patients were treated with post-operative RT to the prostate bed and 2-year AS. Radiation doses and fractionation schedules were 6000–6600 cGy over 30–33 fractions. RT was delivered with a 4-field technique and 18 MV photons. The target volume of RT was limited to the prostate bed and peri-prostatic tissue and no attempt was made to treat regional pelvic lymph nodes. Androgen suppression was initiated within 2 weeks after RT and consisted of nilutamide for 4 weeks and busereline acetate (LHRH analogue) 6.3 mg q 2months for 2 years. Laboratory investigations including Hb, MCV, platelet count, hematocrit, serum testosterone and PSA were performed at baseline, 2 weeks after RT (just prior to the start of busereline acetate), q 4months during the 2-year AS and q 6months thereafter. A Quality of Life Questionnaire (EORTC QLQ-30 version 3) was administered at each of these visits. Three domains (global health status, physical functioning and fatigue) were examined for potential correlation with the pattern of Hb change. The study closed in May 2002 and accrued a total of 79 patients. Of these, 72 were the basis for evaluations of the effect of 2-year AS on Hb. Seven patients were excluded: 4 had insufficient data and 3 patients had co-morbid conditions (carcinoma of rectum, polycythemia vera, and bladder carcinoma), which potentially could confound our analysis. Mean age was 64.2 years. Median interval from surgery to post-operative RT was 4 months. Mean Hb at baseline was 148.4 g/L. RT caused a small, non-statistically significant, decline in mean Hb (2.2 g/L). The maximal decrease in mean Hb during 2-year AS was 10.5 g/L (a significant decline from the baseline, p < 0.001). The rate of decline was initially rapid (-6.04 g/L in the first 4 months of AS), and then slowed down (- 0.34gm/L over the subsequent 4 months), reaching a plateau between 12 and 16 months after initiation of AS. On cessation of the AS, the recovery of Hb was initially slow (+0.35 g/L over the first 6 months), but picked up the pace over the subsequent 6 months (+2.0 g/L). The time interval for mean testosterone and Hb levels to recover to pretreatment levels after cessation of AS appeared to be 2 years. The baseline Hb and the rate of its decline and recovery were not correlated with age. The pattern of Hb decline and recovery mirrored those of serum testosterone. The patterns of hematocrit changes were similar to those of mean Hb. Mean corpuscular volume and platelet count did show any significant decline during 2-year AS. It was difficult to separate the effect of Hb decline on QoL from that of androgen deprivation. However, with this extent of drop in mean Hb (10.5g/L), there was no significant decline in the three QoL domains we examined. There was statistically significant drop in mean Hb during 2-year AS (−10.5 g/L). The decline was rapid initially and reached a plateau at 12–16 months. Its recovery was closely correlated with that of serum testosterone. There are no significant changes in the QoL domains with this extent of Hb decline