Change In Hb Level Research Articles

Changes in maternal hemoglobin during pregnancy and birth outcomes.

BackgroundThe relationship between maternal hemoglobin (Hb) levels during pregnancy and birth outcomes has been controversial. Changes in Hb level during pregnancy may have an impact on birth outcomes. This study aimed to investigate whether changes in Hb levels from early to mid- or late pregnancy is associated with birth outcomes.MethodsParticipants were singleton mothers who delivered at the National Center for Child Health and Development between 34 and 41 weeks of gestation in 2010 and 2011 (n = 1,986). Hb levels were measured at three time points: early (<16 weeks), mid- (16–27 weeks), and late (28–36 weeks) pregnancy. Associations between changes in Hb levels from early to mid- or late pregnancy and birth outcomes (birth weight, Z-score of birth weight, placental weight, and placental ratio) were assessed by multiple regression, adjusting for maternal and fetal covariates.ResultsA smaller reduction in Hb levels from early to mid- or late pregnancy was significantly associated with lower birth weight, Z-score of birth weight, placental weight, and placental ratio. Compared to women with an intermediate reduction from early to late pregnancy, women with the least reduction had a significantly increased risk of delivering low birth weight (LBW) (adjusted odds ratio [aOR], 2.0; 95% confidence interval [CI], 1.3-3.1) and small-for-gestational-age (SGA) (aOR, 1.6; 95% CI, 1.04-2.3) infants, while women with the greatest reduction had a significantly decreased risk of delivering SGA (aOR, 0.38; 95% CI, 0.23-0.65) infants, but an increased risk of high placental ratio (aOR, 1.7; 95% CI, 1.2-2.5).ConclusionsHb changes from early to mid- or late pregnancy were inversely associated with birth weight, placental weight, and placental ratio.

Recommended Usage of Epoetin Alpha Biosimilar Retacrit™: A Subanalysis of the Orheo Study

IntroductionChemotherapy-induced anaemia (CIA) is a frequent complication of patients (pts) with cancer, associated with fatigue and impaired quality of life, and may have serious medical consequences that can lead to discontinuation or interruption of chemotherapy (CT). Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend epoetin treatment of CIA to increase haemoglobin (Hb) levels and to help to prevent red blood cell transfusions and related complications. Several epoetin alpha biosimilars are currently approved for use in the EU for the treatment of CIA. The ORHEO study (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France that evaluated the changes in Hb level in pts with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the EORTC guidelines, with respect to efficacy and safety.MethodsPts >18 years with CIA (Hb <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for EAB treatment were included in this study. Pts were monitored at the start of EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL or Hb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point.ResultsData from 2310 pts (mean age ± standard deviation 66.5±11.8 years) from 232 centres were included in the study analysis. Overall, 79.6% of pts had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those pts with solid tumours, 30.1% of pts had a stage III and 21.6% had a stage IV tumour. Mean baseline Hb level across all pts was 9.6 g/dL, with 35.6% of pts having moderate anaemia (Hb 8–9.5 g/dL).Almost all pts (99.9%) received the epoetin alpha biosimilar (Retacrit™, Hospira UK Ltd., median dose 30,000 IU/week). Overall, 43.8% of pts received the recommended dose of EAB (as determined by their weight) throughout the study. The proportion of pts receiving the recommended dose showed little variation between malignancies (lymphoma: 43.6%; myeloma: 40.9%; breast: 39.3%; lung: 48.3%; colorectal: 39.5%). Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. The overall mean change in Hb level was 1.5±1.6 g/dL at M3 and 1.72±1.61 g/dL at M6. Responses to treatment at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of pts receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with pts who did not receive the recommended dose (9.9 vs 9.0%). Overall, transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively.ConclusionIn the ORHEO study, 44% of pts received the EORTC recommended dose of EAB over the 6-month course of the study. However, the response to therapy was similar regardless of dose. Furthermore, the frequency of overall AEs at M6 did not vary depending on dose.In conclusion, the EAB Retacrit™ was effective and well tolerated in the management of CIA in pts with solid tumours, lymphoma and myeloma and provides an alternative therapeutic option for the treatment of CIA. DisclosuresMichallet:MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria. Soubeyran:Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria; Hospira: Honoraria. Kurtz:Hospira: Coverage of travel expenses/congress fees Other. Albrand:Hospira: Employment.

A randomized crossover study of single biweekly administration of epoetin-α compared with darbepoetin-α in chronic kidney disease patients not receiving dialysis

BackgroundRecent evidence demonstrates that high doses of epoetin-alpha (EPO-α) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-α compared with darbepoetin-alpha (DA-α) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-α is as effective as DA-α for anemia in chronic kidney disease (CKD) patients not receiving dialysis. MethodsSixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-α (10,000 unit) or DA-α (50μg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-α and DA-α treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. ResultsThe mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. ConclusionBiweekly high doses of EPO-α therapy may be equally as effective as Q2W DA-α therapy in maintaining target Hb levels in non-dialysis CKD patients.

Brain Activity during Stereognostic Discrimination Using the Tongue Measured By Functional Near-Infrared Spectroscopy

We previously reported our investigation of the stereognostic ability of the tongue to recognize the shape and size of materials in the mouth and its clinical applications. In the present study, we observed brain activity while performing stereognostic discrimination using the tongue; the changes in levels of oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total-Hb) in the frontal cortex area of 37 healthy individuals (18–75 years old) were measured using a functional near-infrared spectrometer with 45 channels. As an experimental task, the stereognostic test piece (TP) was placed on the center of the tongue dorsum, and subjects moved the TP for shape discrimination without letting it touch the teeth or gums. As a control task, subjects did not move the TP placed on the tongue. Stereognostic task-attributed changes in Hb levels were obtained by subtracting the Hb level of the control task from that of the experimental task. During the stereognostic task, oxy-Hb levels increased in the frontal cortex, including the prefrontal area, in most subjects. However, the results also demonstrated large individual variability. When the degree of change in Hb levels during the stereognostic task was mapped, it was found that the changes in the oxy- and total-Hb levels were similar, while the deoxy-Hb level did not change to the same degree. When subjects were divided into three groups, highly-, moderately- and mildlyincreased oxy-Hb levels, there was a significant negative correlation between age and degree of oxy-Hb level increase. The present study suggests stereognosis may be involved in several different information processing pathways, and that aging may also be a factor in the large variability we observed.

Intravenous iron supplementation may be superior to observation in acute isovolemic anemia after gastrectomy for cancer

To determine whether the application of post-operative intravenous (IV)-iron for acute isovolemic anemia after gastrectomy for cancer may be effective. Among 2078 gastric cancer patients who underwent surgery between February 2007 and August 2009 at the National Cancer Center Korea, 368 patients developed post-operative anemia [hemoglobin-(Hb)-level < 9 g/dL] within the first postoperative week. Patients requiring transfusions were excluded. IV-iron was administered to 63 patients (iron group). Sixty patients were observed without treatment (observation group). The clinical outcomes of the groups were compared concerning clinicopathologic data, morbidity, and changes in Hb levels using Fisher's exact test, Student's t-test and the Z-test. The initial Hb level was higher in the iron group than in the observation group (7.3 ± 1.0 g/dL vs 8.4 ± 0.5 g/dL, P < 0.001). The slope of the changes in the Hb level was significantly higher in the iron group than in the observation group (0.648 ± 0.054 vs 0.349 ± 0.038, P < 0.001). The Hb level 1 and 3 mo post-operatively increased from 10.7 ± 1.3 to 11.9 ± 1.3 g/dL in the iron group (P = 0.033) and from 10.1 ± 1.0 to 10.8 ± 1.4 g/dL in the observation group (P < 0.001). The postoperative hospital stay was significantly longer in the iron group than in the observation group (10.5 ± 6.8 d vs 7.6 ± 5.5 d, P = 0.011). There were no significant differences in the major and surgical complications between the groups (6.3% vs 13.3%, P = 0.192; 9.5% vs 3.3%, P = 0.164). IV-iron supplementation may be an effective treatment for post-operative isovolemic post-gastrectomy anemia and may be a better alternative than observation.

Higher Level at Admission and Subsequent Decline in Hemoglobin in Patients With Acute Pulmonary Edema

Acute pulmonary edema (APE) often occurs without remarkable fluid retention, and the benefits of diuretics are unclear in such patients. Although aggressive diuresis induces an increase in intravascular substances including hemoglobin (Hb), acute changes in Hb level remain to be investigated. We analyzed 237 consecutive acute heart failure patients (74±12 years; 60.8% men) without shock, hemodialysis, bleeding, or urgent coronary angiography. APE was defined as acute onset of dyspnea within the preceding 6h and radiographic alveolar edema requiring immediate airway intervention. At admission, Hb level was higher in APE (n=29) than non-APE patients (n=208; 13.4±2.2 vs 12.2±2.1g/dl, P<0.01). Although diuretic therapy was performed in 232 patients (97.9%), hemoconcentration (ie, any increase in Hb) was observed in only 64 patients (27.0%) at 24h after admission. Conversely, Hb level decreased in both groups and the difference was larger in APE patients (-1.8±1.1 in APE and -0.5±1.0g/dl in non-APE patients, P<0.001). APE was significantly related to a greater decrease in Hb after adjusting for baseline Hb (β=-1.08g/dl, SE=0.20, P<0.001, ANCOVA). APE patients had higher Hb level at admission and a more remarkable decline in 24h than did those without APE. Acute change in Hb might be caused by factors other than diuresis-induced hemoconcentration. The present findings may be useful in the selection of diuretic strategies.

AB0569 Effects of tocilizumab in combination with non biologic DMARDS on early improvement of anemia and fatigue in adult patients with moderate to severe active rheumatoid arthritis

BackgroundA significant number of RA patients (pts) have low haemoglobin (Hb) levels. Normalisation of Hb in anaemic RA pts may be a suitable marker of improvement in disease activity, as...

Hospitalization and Mortality in Hemodialysis Patients: Association with Hemoglobin Variability

Background/Aims: Hemodialysis patients show complications associated with low or high hemoglobin (Hb), which occur frequently in clinical practice. We sought to determine the clinical importance of these changes in Hb levels. Methods: From our clinic cohorts, we identified 1,634 who met inclusion criteria for analysis of hospitalization frequency and 1,953 analysis of mortality; many patients were in both groups. Hb excursions outside the target range (11-12.5 g/dl) were studied in relation to patient outcomes. Results: Hb measures below range were associated with more frequent hospitalization (p < 0.001), increased length of stay (p < 0.001), and increased mortality (p < 0.01), whereas Hb above range was associated with a reduced frequency of hospitalization (p < 0.01) and shorter length of stay (p < 0.01), and tended to be associated with reduced mortality. Conclusions: Excursions below range were associated with negative outcomes, but excursions above range were either beneficial or neutral. Our findings indicate that clinicians should focus on low Hb as a negative indicator of patient status, whereas transient Hb above range is a marker for patient health and well-being.

Middle cerebral artery Doppler and hemoglobin changes immediately following fetal transfusion

Objective: To determine the relationship between the change in middle cerebral artery peak systolic velocity (MCA-PSV) and the change in fetal Hemoglobin (Hb) immediately following intrauterine transfusion (IUT). Materials and methods: Study data included all IUTs performed for suspected fetal anemia from 2007–2011. Results: Sixty-eight IUTs were performed for 23 pregnancies, demonstrating a statistically significant MCA-PSV decrease for up to four IUTs. Significant correlations between changes in Hb levels and MCA-PSV were not detected. Conclusion: MCA-PSV values were highly variable in the immediate post-operative period and did not correlate with the Hb change.

1563P - The Use of Biosimilars in the Management of Chemotherapy-Induced Anaemia (CIA) in Solid Tumours, Lymphoma and Myeloma: the Orheo Study

ABSTRACT The approval of epoetin biosimilars in the European Union requires extensive scientific evaluation and stringent regulatory procedures, including post-marketing studies. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational, longitudinal, multicentre study performed in France to evaluate the efficacy and safety of biosimilar epoetins for the treatment of CIA in the clinical setting. Patients >18 years with CIA (haemoglobin [Hb] 2310 patients (mean age 66.5 years) from 232 centres were included, of whom 79.6% had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those patients with solid tumours, 30.1% of patients had a stage III and 21.6% had a stage IV tumour. Almost all patients received the biosimilar epoetin zeta (Retacrit®, Hospira UK Ltd., median dose 30,000 IU/week). Mean baseline Hb level across all patients was 9.6 g/dL, with 35.6% of patients having moderate anaemia (Hb 8–9.5 g/dL). Following treatment, Hb response was achieved in 81.6% and 86.5% of patients at 3 and 6 months, respectively. The overall mean change in Hb level was 1.5 ± 1.6 g/dL at 3 months and 1.72 ± 1.61 g/dL at 6 months. Transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively. In conclusion, Retacrit was effective and well tolerated in the management of CIA in patients with solid tumours, lymphoma and myeloma. Disclosure M. Michallet: I received honoraria from Hospira for advisory boards and consulting, P. Soubeyran: I received honoraria from Hospira for advisory boards and consulting, H. Albrand: Employed by Hospira, E. Luporsi: I received honoraria from Hospira for advisory boards and consulting.

Darbepoetin alfa

Darbepoetin alfa

Prise en charge de l’anémie en oncologie: modalités pratiques, efficacité des agents stimulant l’érythropoïèse (ASE) [darbépoétine alpha] et place de la transfusion

Patients andmethodAn observational study was carried out in an oncology department that had initiated an active anaemia management strategy using ESA (darbepoetin-alpha) in order to observe the resulting changes seen in the use of transfusions and to assess the effectiveness of this strategy in controlling anaemia in clinical practice. Data were gathered from medical files of all patients treated with ESA for anaemia during two successive periods of a year. The first period corresponded to the implementation of this strategy within the unit (from September 2006), and the second period (from April 2008) could be regarded as a phase of stable practice.ResultsThe percentage of patients treated with ESA increased slightly, from 23.3 to 26.8%, for the active group, which remained almost identical during the two periods (897–899 patients). The average number of ESA injections per patient decreased (3.21 compared to 2.88, NS). The number of transfusions reduced by about 19% across the two periods. Analysis of the effectiveness of treatment was carried out on a cumulative number of 339 patients, who received a continuous sequence of ESA injections during the same course of chemotherapy, with at least three injections of ESA. This corresponded to 205 patients in period one and 134 patients in period two. Effectiveness was defined as a function of the changes in Hb level (ΔHb) in three categories: 39.8% of patients were judged to have responded well (ΔHb ≥ 1 g/dl), 36.9% as having had an intermediate response (0 ≤ δHb < 1 g/dl) and if ΔHb < 0, they were classified as not responded (33.3%). Improvements in Hb levels during successive ESA injections were more significant for patients presenting with initially low Hb levels.ConclusionsThe results obtained show that the effectiveness of darbepoetin-alpha observed in clinical practice is in agreement with that demonstrated in clinical trials, and confirms that treatment with darbepoetin-alpha substantially decreases the need for transfusions.

Influence of Linezolid Clearance on the Induction of Thrombocytopenia and Reduction of Hemoglobin

IntroductionAlthough linezolid (LZD) has proven effective for the treatment of infections caused by multidrug-resistant Gram-positive cocci, thrombocytopenia and anemia associated with reduced hemoglobin (Hb) levels are common side effects. To study the association between the development of these adverse effects and blood LZD levels, the authors evaluated the correlation between LZD clearance (LZD-CL), platelet (PLT) counts and Hb levels. MethodsSixteen patients with methicillin-resistant Staphylococcus aureus infection were administered LZD over a period of 4 to 41days, and blood was collected at variable time points beginning on day 4 (n=31). Blood LZD levels were measured by high-performance liquid chromatography, and LZD-CL was estimated by the population pharmacokinetics mean parameter and Bayesian methods. The relationship between the estimated LZD-CL and reductions in PLT counts and Hb levels was then evaluated by regression analysis. ResultsDuring the LZD treatment period, a weak correlation was identified between the LZD-CL rate and PLT counts (r2=0.31, n=31). Significantly, the regression analysis between LZD-CL and Hb levels showed a stronger correlation (r2=0.54, n=31), with Hb levels clearly decreasing with reductions in the LZD-CL rate. ConclusionsIn patients undergoing treatment with LZD, low LZD-CL rates correlated with reductions of both PLT counts and Hb levels, suggesting that increase of blood LZD levels influences hematopoietic function. Because a strong correlation was noted between LZD-CL and Hb levels, closely monitoring changes in Hb levels during treatment with LZD may detect the development of adverse effects such as thrombocytopenia and anemia.

Pharmacological Inhibition of Calpain-1 Prevents Red Cell Dehydration and Reduces Gardos Channel Activity in a Mouse Model of Sickle Cell Disease. Identification of Druggable Protease Target

Abstract 852Sickle cell disease (SCD) is a hereditary red cell disorder characterized by the presence of pathological HbS, which polymerizes upon deoxygenation promoting red blood cell (RBC) dehydration and sickling. In SCD, the dense RBCs play a crucial role in the pathogenesis of sickle cell related organ damage and clinical manifestations. Although progress has been made in pathogenesis of SCD, the treatment options for SCD have limited pharmacological tools for clinical practice. Calpains are ubiquitous calcium-activated cysteine proteases, causing controlled proteolysis of protein substrates with regulatory functions. RBCs express only calpain-1, whose physiological function remains poorly understood. Gene inactivation of mouse calpain-1 revealed differential regulation of RBC calcium pump and enhanced RBC hydration. To investigate the relevance of these findings in SCD, we used BDA-410, a novel orally active inhibitor of calpain-1. Using the sickle (SAD) mouse, a model for human sickle cell disease, BDA-410 was administrated at the dosage of 30 mg/K/d by gavage to wild-type (WT) and sickle cell (SAD) mice. Animals were divided into 4 groups of 6 mice each: two groups from each strain were treated with BDA-410 for 14 days along with vehicle controls. Mice at baseline, day 7, and day 14 of BDA-410 treatment were evaluated for hematological parameters including the RBC density profile with phthalate density curves, RBC cation content, and Ca2+ activated K+ channel (Gardos channel) activity. BDA-410 induced a significant increase in Hct in both WT and SAD mice with no significant changes in Hb levels and an associated increased in MCV. The red cell K+ content increased significantly in SAD RBCs at day 7 and 14 of inhibitor treatment as compared to untreated SAD mice; whereas no major changes were observed in the WT RBCs. The mean corpuscular Hb concentration (CHCM) decreased in both WT and SAD mice treated with BDA-410. A left-shift in the RBC density curves was observed in SAD mice; whereas this left-shift was limited to a sub-fraction of denser red cells in the WT mice. The activity of the Gardos channel was significantly reduced in BDA-410 treated SAD mice compared to the untreated SAD group, while no significant differences were observed in the WT mice. Since the membrane-association of Peroxiredoxin-2 (Prx2) is increased in SCD RBCs, and has been correlated with Gardos channel activity, we evaluated Prx2-membrane association. BDA-410 treatment induced a significant reduction in the amount of Prx2 translocated to the membrane in both WT and SAD mice. Moreover, when we exposed WT and SAD mice to hypoxia (8% oxygen) for 48 hours, followed by 2 hours of re-oxygenation to mimic sickle cell related vaso-occlusive events, BDA-410 treatment prevented the hypoxia induced K+ loss and RBC dehydration in SAD mice. Identification of RBC membrane substrates in the calpain-1 null mice suggests that proteolytic modification of clapain targets as calcium pump, Prx2, and the Gardos channel protein may underpin some of the protective effects of BDA-410 in SAD mice. These results suggest that the inhibition of calpain-1 may offer a new therapeutic strategy to ameliorate hematological phenotype of SCD. Disclosures:No relevant conflicts of interest to declare.

The effects of oral iron supplementation on the progression of anemia and renal dysfunction in patients with chronic kidney disease

Oral iron traditionally has been administered to patients with chronic kidney disease (CKD). However, there are limited data on the effect of oral iron in CKD patients. Here, we evaluate the effects of oral iron therapy on renal anemia and progression of renal disease in CKD patients. Anemic patients with nondialytic CKD who were naive to erythropoiesis-stimulating agents (ESAs) were recruited for the prospective observational study. The participants were classified into oral iron or control group, and they were asked to keep their treatment status for 1 year. The primary outcomes were change in Hb and estimated glomerular filtration rate (eGFR). A total of 182 participants were enrolled and 138 completed a 12-month follow-up. No change in Hb level was observed during the follow-up period in the iron group, whereas a significant decrease in Hb was observed in the control group. Oral iron supplementation was effective, especially in patients with eGFR < 30 ml/min/1.73 m2. The changes in eGFR did not differ between the two groups. The incidences of drug-related adverse events were equivalent in two groups. Oral iron supplementation might attenuate the progression of anemia in nondialytic CKD patients without ESAs and not impact kidney function.

Role of Iron Supplementation to Erythropoiesis Stimulating Agents In the Management of Chemotherapy-Induced Anemia In Cancer Patients: A Systematic Review and Meta-Analysis

AbstractAbstract 2055 Background:Erythropoiesis stimulating agents (ESAs) are commonly used to treat chemotherapy-induced anemia (CIA) in cancer patients. However, numerous clinical trials indicate that about half of the patients fail to show an increase in hemoglobin (Hb) levels or a reduction in red blood cell (RBC) transfusions following treatment. This may be attributed to functional iron deficiency (FID) experienced by these patients. Iron is often used to supplement ESAs to correct the FID. However, no systematic review has been conducted that tackles the role of iron supplementation. This is the first systematic review and meta-analysis that addresses the efficacy and safety of iron supplementation to ESAs in the management of CIA. Methods:Literature search of PubMed, Cochrane databases and meetings abstracts from American Society of Clinical Oncology, American Society of Hematology and European Hematology Association was undertaken to identify phase III RCTs published until June 2010. No limits were used in the search. We extracted data on hematopoietic response rate, time to hematopoietic response, RBC transfusions, mean change in Hb level, quality of life (QOL), overall survival (OS), and grade III-IV treatment related harms. We conducted subgroup analyses based on type and route of administration of iron. Time to event data, dichotomous data, and ratio level data were pooled as hazard ratios, risk ratios (RR), and mean difference (MD), respectively, under the random effects model. Results:Seven RCTs (5 full papers and 2 meeting abstracts) were included enrolling 1,777 patients. For the outcome of hematopoietic response, there was a beneficial effect of iron supplementation to ESAs compared with ESAs alone (RR= 0.65, 95% CI: 0.53 – 0.79). However, for this outcome, RCTs which used intravenous iron favored ESAs and iron (RR= 0.57, 95% CI: 0.44 – 0.74), whereas no differences were found in RCTs using oral iron (RR= 0.81, 95% CI: 0.64 – 1.03) (test of interaction: p= 0.02). No differences were found in the median time to hematopoietic response between patients receiving ESAs and iron versus those receiving ESAs alone. Significantly fewer patients treated with ESAs and iron required RBC transfusions compared to the number treated with ESAs alone (RR= 0.67, 95% CI: 0.52 – 0.86) (Table 1). There were no differences in RBC transfusions based on the route of iron administration. Although mean change in Hb level data was reported in 71% of studies (5/7), data were extractable for meta-analysis from only 43% of RCTs (3/7). The mean change in Hb level was significantly greater in patients receiving ESAs and iron (MD = 0.77, 95%CI: 0.27–1.28) compared with ESAs alone. QOL was reported in three studies, but due to variation in the scales used (FACT-F and LASA) we were unable to provide a pooled estimate. In trial by Bastit et al., no differences in the QOL were found between patients treated with ESA and iron versus those treated with ESAs alone. In the trial by Auerbach et al., patients receiving ESAs and iron had statistically significant better QOL than those receiving ESAs alone. None of the included RCTs reported OS estimates. No differences were found related to risk of grade III-IV thromboembolic events between patients receiving ESAs and iron versus patients receiving ESAs alone (RR= 1.09, 95% CI: 0.55 – 2.18, p= 0.807, 3 RCTs, 614 patients). Type of iron used (gluconate vs. dextran vs. sucrose vs. sulphate) had no impact on any outcome. Conclusion:Compared with ESA alone/placebo, iron supplementation to ESAs significantly increases hematopoietic response rates and reduces number of RBC transfusions in patients with CIA. Intravenous iron appears to be superior to oral iron in achieving hematopoietic response. Both treatments are well tolerated with no significant differences in adverse events.Table 1Summary of ResultsOutcomeRR95% CIp-valueI2# RCTs# patientsNNTHematopoietic response0.650.53, 0.79<.00160.7%71777NNT: 4-11Transfusions0.670.52, 0.860.0020.0%71777NNT: 13-150Note: RR=Risk Ratio; CI=Confidence Interval; NNT=Number Needed to Treat Disclosures:No relevant conflicts of interest to declare.

Efficacy and Tolerability of Zidovudine 200 mg Twice a Day as Part of Combination Antiretroviral Therapy for 96 Weeks

Efficacy and Tolerability of Zidovudine 200 mg Twice a Day as Part of Combination Antiretroviral Therapy for 96 Weeks

Continuous fall in hemoglobin level is a poor prognostic factor in patients with nasopharyngeal carcinoma treated with radiotherapy

Anemia can not only reduce the quality of life of patients with cancer, but also affect their survival. This study was to investigate the prognostic value of hemoglobin (Hb) level in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy. Clinical data of 520 NPC patients received definitive radiotherapy between 2000 and 2002 at Sun Yat sen University Cancer Center were analyzed. Patients were stratified into normal Hb level and anemia groups according to their Hb levels before, during, and after radiation. Anemia was defined according to World Health Organization criteria as Hb level < 130 g/L in men and < 120 g/L in women. Hb continuous decrease group and non decrease group were defined according to Hb changes in the patients during radiotherapy. Loco regional recurrence free survival (LRFS) and overall survival (OS) rates were estimated using the Kaplan Meier method. Multivariate analysis was performed using the Cox model to analyze the prognostic factors. Before radiation, the 5 year LRFS rates were 60.9% in anemia group and 63.9% in normal Hb level group (P = 0.337); the 5 year OS rates were 65.2% and 71.0%, respectively (P = 0.299). During radiation, the 5 year LRFS rates were 56.7% in anemia group and 67.9% in normal Hb level group (P = 0.013); the 5 year OS rates were 61.0% and 75.9%, respectively (P = 0.001). After radiation, the 5 year LRFS rates were 59.6% in anemia group and 64.9% in normal Hb level group (P = 0.169); the 5 year OS rates were 65.0% and 71.9%, respectively (P = 0.090). The 5 year LRFS and OS rates were significantly lower in Hb continuous decrease group than in Hb non decrease group (59.1% vs. 69.3%, P = 0.032; 66.2% vs. 76.4%, P=0.011). Multivariate analysis showed that the continuous decrease of Hb was an independent prognostic factor for OS. The change in Hb level during radiotherapy is an important prognostic factor affecting the OS of NPC patients.

Trajectory of Hemoglobin (Hb) in Patients Receiving Erythropoiesis-Stimulating Agents (ESAs) for Anemia Due to Concomitantly Administered Myelosuppressive Chemotherapy (CIA) (2006∼2008).

Abstract 1399Poster Board I-421 Purpose:Anemia, a common hematologic complication of cancer and myelosuppressive chemotherapy, is often treated with ESAs, which include darbepoetin alfa (DA) and epoetin alfa (EA). Since 2007, the use of ESAs in CIA has been increasingly restricted in product labels, reimbursement, and practice guidelines. Prior analyses have indicated increasing transfusion rates over this period among CIA patients in the community setting. Little is known about the trajectory (or time path) of Hb levels prior to and after initiation of ESA therapy in real world practice. In particular, it is unknown whether recent ESA utilization restrictions have affected the change in Hb levels that chemotherapy patients experience prior to and after ESA initiation. This study analyzed Hb trajectories in CIA patients receiving ESAs from 2006 - 2008. Methods:ESA episodes of care (ESA EOCs) within episodes of chemotherapy care (EOCCs) were identified from 2006 to 2008 in an oncology electronic medical records database of approximately 250,000 cancer patients receiving care from 111 practice sites across 25 states. An EOCC was identified by a gap of ≥90 days with no evidence of chemotherapy use. An ESA EOC was identified by a gap of ≥42 days without ESA therapy. To measure Hb trajectory over time, the difference between Hb at ESA initiation (baseline Hb) and mean Hb in each of the 6 weeks before and 6 weeks after ESA initiation was computed. Differences in means were compared by t-tests. Analysis of variance was done to test whether the differences differed by calendar year. Results:From 2006 to 2008, 22,357 ESA episodes were identified (EA: n=6,117, DA: n=16,420). Compared to 2006 (mean Hb=10.7 g/dL), ESAs were initiated at progressively lower baseline Hb levels overtime, 0.3 g/dL lower in 2007 (p<.001) and 1.0 g/dL lower in 2008 (p<.001). Average time from start of chemotherapy to initiation of ESA therapy increased from 44 days in 2006 to 66 days in 2008 (p<.001). Over the study period, mean Hb declined 1.3 g/dL in the 6 weeks prior to ESA initiation, and increased 0.7 g/dL in the 6 weeks after initiation. In the 6 weeks prior to ESA initiation, Hb decline was slightly different by calendar year (mean Hb decline 2006: 1.2 g/dL, 2007: 1.3 g/dL, 2008: 1.4 g/dL; p<0.050); in the 6 weeks after ESA initiation, Hb increase was not significantly different among the three years (mean Hb increase 2006: 0.7 g/dL, 2007: 0.7 g/dL, 2008: 0.8 g/dL; p=0.128). Conclusions:In patients with CIA treated with ESAs between 2006 and 2008, Hbs at ESA initiation progressively declined likely in response to the changes in product labels, reimbursement and practice guidelines. There were no clinically significant differences in the rates of Hb changes observed from 2006 to 2008 before and after ESA initiation. Further research is needed to determine if earlier initiation of ESA therapy may help maintain Hb levels, improve patient's clinical outcomes and/or offset other health services such as the use of transfusions. Disclosures:Hill: Amgen, Inc.: Research Funding. Cong: Amgen, Inc.: Employment. Hess: Amgen, Inc.: Research Funding. Nordyke: Amgen Inc.: Employment.

Risk factors for postoperative systemic complications in elderly patients with brain tumors

In elderly patients with brain tumors, the prevention of postoperative systemic complications is extremely important, and identification of the risk factors would be useful for planning therapy. The authors investigated ways to avoid postoperative complications by identifying risk factors. The study population included 84 patients, 70 years of age or older, who underwent surgical brain tumor removal. The following independent factors were assessed by univariate and multivariate analyses: sex, age, preoperative underlying diseases and complications, histopathological findings, preoperative Karnofsky Performance Scale (KPS) score, preoperative whole blood hemoglobin (Hb) level, preoperative serum total protein (TP) level, operation time, intraoperative blood loss, change in Hb level (difference between pre- and postoperative values), and change in TP level (difference between pre- and postoperative values). The cutoff values for significant independent factors were also determined. Overall, 35 (41.7%) of the 84 patients had a total of 56 postoperative systemic complications. Univariate analysis identified the preoperative KPS score, intraoperative blood loss, change in Hb level, and change in TP level as risk factors for postoperative complications, and multivariate analysis extracted the following risk factors: the preoperative KPS score (p = 0.0450, OR 4.020), intraoperative blood loss (p = 0.0104, OR 6.571), and change in Hb levels (p = 0.0023, OR 9.301). The cutoff values were: KPS score < 80%, intraoperative blood loss >or= 350 ml, and change in Hb level >or= 2.0 g/dl. In elderly patients with brain tumors, low preoperative KPS score, high intraoperative blood loss, and a large difference between pre- and postoperative Hb levels are significant risk factors for postoperative systemic complications.