Mean Increase In Hb Research Articles

A Study of Ormeloxifene in Case of Dysfunctional Uterine Bleeding

<strong>Background:</strong>Menorrhagia accounts for 12% of all gynaecology consultations and is one of the most common causes of iron deficiency anaemia in females after nutritional anaemia.<p><strong>Objectives:</strong> To evaluate the efficacy and side effects of ormeloxifene in cases of dysfunctional uterine bleeding.</p><p><strong>Material and Methods:</strong> 30 women aged 28-46 years who attended the outpatient gynaecology department in a tertiary care hospital with complaint of heavy menstrual flow were recruited for the study. Two pretreatment baseline cycles were compared to the treatment cycles of ormeloxifene. The main outcomes measured were menstrual blood, blood haemoglobin levels and endometrial thickness in proliferative phase as studied by TVS. Data thus collected was compared and analysed statistically.</p><p><strong>Results:</strong> Total number of bleeding days per year decreased by 76%. Total no. of pads soiled per cycle decreased by 76.3%. All the patients reported disappearance of clots, 66.66% within 1 month of the treatment only. Dysmenorrhoea was relieved in 62.5% patients. Mean increase in Hb was 0.42g%.</p><p><strong>Conclusion:</strong> Ormeloxifene is very effective in improving all the parameters of blood loss in DUB including the no. of days of bleeding, no. of pads soiled and the passage of clots. Ormeloxifene has a good patient acceptability and compliance due to its minimal side effects, low cost and simple dosage schedule. In the peri-menopausal age group, drug is protective against breast malignancy and osteoporosis. Ormeloxifene has the potential to be an effective treatment for DUB and should always be considered amongst the treatment options.</p>

A multicenter, randomized, active‐controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia

Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses. We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

Quantitative Assessment of Changes in Trabeculectomy Blebs After Laser Suture Lysis Using Anterior Segment Coherence Tomography

To quantify changes in bleb morphology after laser suture lysis (LSL) using anterior segment optical coherence tomography (AS-OCT). This was a prospective observational case series of patients who underwent trabeculectomy surgery with mitomycin-C and required subsequent LSL. Subjects were assessed before and immediately after LSL, and at 3 months after LSL. At each visit, a standardized cross-sectional AS-OCT image of the bleb was obtained, from which a masked observer measured bleb height (hB), cavity height (hC), wall cross sectional area (AW), cavity cross sectional area (AC), and bleb cross sectional area (AB) using custom software. Twenty-five subjects (25 eyes) were examined. LSL was performed at a mean of 21.5±16.3 days after trabeculectomy. Immediately after LSL, there was a significant increase in mean hB (P=0.026) and mean hC (P=0.45) from pre-LSL. At 3 months after LSL, there was a significant increase in mean hB (P=0.003), mean AC (P=0.047), and mean AB (P=0.006) as compared with before LSL. Increase in hB and hC immediately after LSL was predictive of outcome at month 3. AS-OCT was able to quantify changes in bleb morphology after LSL, some of which were predictive of eventual outcome.

Time course of the hemoglobin mass response to natural altitude training in elite endurance cyclists

To determine the time course of hemoglobin mass (Hb(mass)) to natural altitude training, Hb(mass), erythropoietin [EPO], reticulocytes, ferritin and soluble transferrin receptor (sTfR) were measured in 13 elite cyclists during, and 10 days after, 3 weeks of sea level (n=5) or altitude (n=8, 2760 m) training. Mean Hb(mass), with a typical error of ∼2%, increased during the first 11 days at altitude (mean ± standard deviation 2.9 ± 2.0%) and was 3.5 ± 2.5% higher than baseline after 19 days. [EPO] increased 64.2 ± 18.8% after 2 nights at altitude but was not different from baseline after 12 nights. Hb(mass) and [EPO] did not increase in sea level. Reticulocytes (%) were slightly elevated in altitude at Days 5 and 12 (18.9 ± 17.7% and 20.4 ± 25.3%), sTfR was elevated at Day 12 (18.9 ± 15.0%), but both returned to baseline by Day 20. Hb(mass) and [EPO] decreased on descent to sea level while ferritin increased. The mean increase in Hb(mass) observed after 11 days (∼300 h) of altitude training was beyond the measurement error and consitent with the mean increase after 300 h of simulated live high:train low altitude. Our results suggest that in elite cyclists, Hb(mass) increases progressively with 3 weeks of natural altitude exposure, with greater increases expected as exposure persists.

Red blood transfusion in preterm infants: changes in glucose, electrolytes and acid base balance

Background:Preterm neonates comprise the most heavily transfused group of patients, and about 85% of extremely low birth weight newborns receive a transfusion by the end of their hospital stay. The aim of this study was to assess the possible metabolic effects of RBC transfusion on preterm infants, especially during the first 2 weeks of life, and its relation to blood volume.Materials and Methods:This study was conducted on 40 preterm neonates with gestational age of less than or equal to 34 weeks. They received RBCs transfusion during first 2 weeks of life. Venous blood samples of infants were collected 2 to 4 hours before and 1 hour after the end of transfusion to evaluate hemoglobin (Hb) level, hematocrit, acid-base, electrolytes, and glucose status. Then, infants were classified into two main groups: those who received RBCs volume less than or 20 ml/kg and those who received RBCs volume more than 20 ml/kg.Results:Infants received a mean volume of 20.38 ± 3.2 ml/kg RBCs (range, 10.9 - 26.6 ml/kg) at a median age of 9.8 ± 3.6 days. After transfusion, a significant increase of mean Hb (P<0.001), mean Hct (P<0.001), pH (P<0.001), pO2 (P<0.05), and a significant decrease of the pCO2 (41.46 ± 8.8torr vs 35.4 ± 9.34 torr; P<0.001) were observed. In addition, there was a significant increase of serum K+ (P<0.001), and a significant decrease of Ca+2 (P<0.001). A positive correlation was found between the K+ intake and the changes of kalemia (r = 0.99; P = 0.00). Furthermore, we observed an inverse correlation between the patients’ calcium intake and the changes of calcemia (r = -0.35; P = 0.02). On comparing the changes in clinical and biochemical variables between two groups after transfusion, we observed a significant increase in mean Hb and Hct associated with a significant decrease in mean serum Ca+2 (P<0.001) in the group receiving the larger blood volume.Conclusion:RBC transfusion was effective in improving anemia, oxygenation, increasing pH, and decreasing CO2 and Ca+2. However, from a more clinically relevant point of view, we demonstrated the development of hyperkalemia, especially in infants with a previously borderline hyperkalemia.

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

Anaemia is a significant prognostic factor in cancer patients receiving anticancer drugs such as methotrexate (MTX). This study focuses on the effects of toxicological changes on the hematopoietic systems in male and female Wistar Hannover rats when MTX is orally administered at a dose of 0, 0.05, 0.15, or 0.45 mg/(kg·day) for a period of 28 days. Both male and female rats receiving 0.45 mg/kg MTX showed a decrease in the haemoglobin concentration (Hb), haematocrit, and erythrocyte count. Female rats showed a decrease in mean corpuscular volume (MCV) and an increase in cell mean Hb (CHCM) in total erythrocytes, including the mature erythrocytes. These results indicate that MTX causes the production of small, mature erythrocytes that contain a high concentration of Hb. MTX reduced the number of peripheral reticulocytes but produced the cells with a large size and a high concentration of Hb, as demonstrated by the reticulocyte MCV and CHCM as well as the content of haemoglobin per reticulocyte (CHr). Consistent with these findings, bone marrow haematopoiesis was impaired by MTX, as there was a reduction in erythroid count in rats of both sexes. The number of cells of the myeloid lineage reduced in female rats, followed by a reduction in the total leukocyte and neutrophil counts in peripheral blood. Thrombocytopenia was detected in a small population of rats. These results indicate that MTX induces hyperchromic microcytic anaemia and pancytopenia, and the use of MCV and CHCM in mature erythrocytes and reticulocytes, along with the CHr, gives a better understanding of the development and nature of anaemia.

Bioavailability of Oral Iron Drugs as Judged by a 59Fe-Whole-body Counting Technique in Patients with Iron Deficiency Anaemia

The bioavailability of the oral iron compound iron(II)-glycine sulfate (ferro sanol duodenal, FSD, 1 x 100 mg Fe/d) was studied in 56 patients with iron deficiency anaemia using a 59Fe-labelling technique and 59Fe-whole-body counting. This technique measures the individual iron loss and allows in patients with substantial blood loss under iron medication a reliable information on the bioavailability of the drug. In all patients, the increased loss of iron (mean 5.8 +/- 4.4 mg/d) was clearly compensated by the iron utilisation (mean: 11.1 +/- 5.6 mg/d) from a daily dosage of 100 mg iron from FSD. A significant increase in the haemoglobin concentration was observed within the monitored treatment period of 6-10 weeks (mean Hb increase from 10.7 +/- 1.7 to 12.1 +/- 1.8 g/dl). FSD has therefore documented a bioavailability of at least 11% from a single daily dose of 100 mg Fe and was effective in the treatment of the anaemia in almost all patients under study.

Pharmacodynamics and safety of ferric carboxymaltose: a multiple-dose study in patients with iron-deficiency anaemia secondary to a gastrointestinal disorder

This multiple-dose Phase I/II study provided pharmacodynamics and pharmacokinetics data on the therapeutic benefit of ferric carboxymaltose (FCM, Ferinject) and evaluated the safety and tolerability of this intravenous (i.v.) iron preparation. Two doses of iron as FCM were given as i.v. infusion over 15 min, 500 mg iron given once weekly for up to 4 weeks (Cohort 1) or 1000 mg iron weekly for 2 weeks (Cohort 2), in patients with a total requirement > or = 1000 mg iron (total cumulative maximum dose < or = 2000 mg iron). Adults with moderate to severe, stable iron-deficiency anaemia (IDA) (haemoglobin [Hb] < or = 11.0 g/dl, serum ferritin < 100 microg/l, transferrin saturation [TSAT] < 16%) due to a gastrointestinal (GI) disorder were included. Pharmacodynamics variables: proportion of patients achieving values within the reference range for Hb (men: 14.0-18.0 g/dl, women: 12.0-16.0 g/dl), serum ferritin (20-500 microg/l), TSAT (16-45%) and proportion of patients with an increase in Hb of at least 2.0 g/dl. Pharmacokinetics variables: total serum iron levels at time of maximum serum iron concentration during the fast elimination phase and at trough time-points. Safety assessments: the incidence of adverse events (AEs) and changes in vital signs, physical examinations, and clinical laboratory parameters. In Cohorts 1 and 2, 14/20 (70%) versus 19/26 (73%) of patients completed the study. Individual calculated iron deficits were 1000-2100 mg. The mean cumulative dose of FCM in Cohorts 1 and 2 was 1800 mg and 1563 mg iron, respectively. At baseline, patients in both cohorts had similar Hb levels (mean 8.7 g/dl in both cohorts). More than 97% of patients demonstrated a clinically meaningful increase in Hb levels (> or = 1.0 g/dl) during the study. By the week 4 follow-up visit, an increase of at least 2.0 g/dl was achieved by 15/20 (75%) and by 19/26 (73.1%) patients in Cohorts 1 and 2, respectively, and the mean increase in Hb was 3.2 g/dl in Cohort 1 and 3.3 g/dl in Cohort 2. By day 28, 3/6 (50%) patients in Cohort 1 had achieved normal Hb levels, and by the 4-week post-treatment followup visit 7/19 patients (37%) in Cohort 1 and 12/25 (48%) in Cohort 2 had reached Hb levels within the reference range. Serum ferritin levels increased rapidly at the start of treatment and remained in the reference range throughout the study; increases were greater in Cohort 2. Mean baseline TSAT values were similar in both cohorts (24.2% in Cohort 1, 20.7% in Cohort 2), and were within the reference range at the week 4 follow-up visit for 41.0 and 39.1% of the patients in Cohorts 1 and 2, respectively. The incidence of AEs occurring after the first administration of FCM (treatment-emergent AEs, TEAE) was generally low and similar in Cohorts 1 (11/20 [55.0%]) and 2 (13/26 [50.0%]). Most TEAEs were mild; only 2/ 20 patients (10.0%) in Cohort 1 and 3/26 (11.5%) in Cohort 2 had TEAEs of moderate intensity. There were no AEs of severe intensity, serious AEs, or deaths. Most AEs were considered by the investigator to be unrelated or unlikely to be related to the study medication. Since accumulation of serum iron was not observed, a dosing interval of 3-4 days (500 mg iron) or 1 week (1000 mg iron) was demonstrated to be adequate. The increase in serum ferritin and TSAT at the 4-week follow-up visit is indicative of a repletion of the iron stores. The results suggest that doses up to 1000 mg i.v. iron administered as FCM over 15 min arewell tolerated and effective in the treatment of patients with IDA due to a GI disorder.

Efficacy and tolerability of intravenous iron dextran and oral iron in inflammatory bowel disease

Iron deficiency anaemia is common in inflammatory bowel disease (IBD); however, the optimum route of administration of iron replacement therapy is unclear. As inflammation may limit the absorption and efficacy of oral iron, we hypothesized that in routine clinical practice IV iron would be more effective than oral iron in patients with IBD matched for disease type, extent and activity. Thirty-three IBD patients who had received IV iron dextran (Cosmofer) in 2008-2010 were identified and matched for age, sex, diagnosis and baseline disease activity, extent and behaviour to IBD patients given oral iron. Patients given IV iron dextran were more anaemic at baseline than those receiving oral iron. Although haemoglobin (Hb) concentrations were normalized in about a third of patients, and increased significantly in both groups, the mean increase in Hb after 8 weeks was greater in the iron dextran group [2.0 g/dl (0.3) vs. 0.6 g/dl (0.1), P<0.0001]. Response to oral or IV iron was unrelated to age, sex, ethnicity, disease duration, extent or activity. Fifteen percent (five out of 33) patients discontinued oral iron because of gastrointestinal side-effects and a further two out of 35 had anaphylactoid reactions to the IV iron dextran test doses. Neither of the iron formulations worsened disease activity. In routine clinical practice, in anaemic patients with IBD of similar type, extent and activity, IV Cosmofer is more efficacious in increasing Hb concentration than oral iron. Active disease does not impair the response to either IV or oral iron in patients with IBD, and neither product itself worsens disease activity.

High transfusion failure rates in Malawian children with severe anaemia following a standard blood transfusion regimen

High transfusion failure rates in Malawian children with severe anaemia following a standard blood transfusion regimen

Impact of hookworm infection and deworming on anaemia in non‐pregnant populations: a systematic review

ObjectivesTo summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.MethodsElectronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.ResultsTwenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13–3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33–3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).ConclusionsAnaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.

ACE-011, a Soluble Activin Receptor Type Iia IgG-Fc Fusion Protein, Increases Hemoglobin (Hb) and Improves Bone Lesions in Multiple Myeloma Patients Receiving Myelosuppressive Chemotherapy: Preliminary Analysis.

Abstract 749 Background:Anemia is frequently observed in multiple myeloma (MM) patients and can result from cumulative marrow suppression by chemotherapy, invasion of bone marrow by tumor cells, renal insufficiency and other causes. The vast majority of therapies approved or in development for anemia target the erythropoietin (EPO) pathway. However, recent studies suggest that the use of recombinant EPO and its derivatives may be associated with an increased risk of mortality by stimulating tumor progression and/or the occurrence of thromboembolic events. The TGF-β superfamily of proteins has been reported to play a major role in red blood cell (RBC) development, but utilizes a fundamentally different pathway from EPO. ACE-011 is a novel, fully human, fusion protein derived from the activin receptor type IIA (ActRIIA) that binds to and prevents signaling of certain members of the TGF-β superfamily through the ActRIIA receptor. In animal studies, administration of ACE-011 has been shown to increase hemoglobin and RBC levels, promote bone formation, and inhibit breast cancer and MM tumor growth. We previously reported significant increases of hemoglobin, RBC levels, and bone mineral density observed in healthy volunteers who received ACE-011 (ASH, 2008). Here, we report the preliminary results of a randomized, double-blind, placebo-controlled study of ACE-011 in MM patients receiving a regimen of melphalan, prednisolone, and thalidomide (MPT). Methods:Patients with stage II/III multiple myeloma and evidence of osteolytic bone disease were eligible to be enrolled in this study, and randomized to receive either up to 4 monthly subcutaneous (SC) doses of ACE-011 at 0.1, 0.3 and 0.5 mg/kg (n=8 each) or placebo (n=6). All patients received a standardized regimen of MPT. Patients could not have received ESAs ≤ 21 days prior to initiation or during the course of study; bisphosphonate (BP) use was allowed only as a continuation of established therapy at stable doses (≥ 2 months). Results:A total of 30 patients were enrolled. The median age was 61.5 years (ranging from 41 to 79 years). Twenty-eight patients had at least one prior MM therapy (range 1-7 prior therapies), and 13 were on stable BPs. A total of 20 patients skipped at least one dose of ACE-011 or placebo based on dose modification rules. Two patients discontinued study drug prematurely: 1 withdrew consent and 1 due to an adverse event. An SAE of sudden death, cause unknown and considered “probably”-related to MPT or “possibly”-related to ACE-011, occurred 18 days after the last dose of ACE-011 (0.1 mg/kg). Dose-dependent increases in hemoglobin were observed after the first dose of ACE-011. After the first dose, the mean maximum Hb increase was 1.3 g/dL (±1.1) in the 0.5 mg/kg cohort compared to 0.68 g/dL (±0.29) in the placebo group. On day 29 of the study, 75% patients had an increase in Hb of ≥1 g/dL in the 0.5 mg/kg cohort compared to 33% in placebo group. A hemoglobin response defined as an increase of at least 1.5 g/dL increase for consecutive 28 days during study was achieved by 10 (45%) ACE-011 treated patients and 1 (17%) patient on placebo. ACE-011 substantially increased BSAP and slightly decreased S-CTX levels among BP-naïve patients. After the first dose of ACE-011, 6 patients (20%) were reported to have ≥10 mm reduction in pain, as measured by the Visual Analog Scale (VAS), which was sustained during the study. A greater trend to improvement in osteolytic lesions by skeletal X-rays was seen in ACE-011-treated patients. Of 22 evaluable patients treated with ACE-011, 7 patients (32%) achieved a CR or VGPR. Conclusions:ACE-011 is well-tolerated and has significant hematologic activity in MM patients receiving myelosuppressive chemotherapy. ACE-011 treatment also demonstrated clinically significant increases in biomarkers of bone formation, improvement in skeletal metastases, decreases in bone pain, and anti-tumor activity. The unique pharmacology of ACE-011 enables it to address multiple complications of MM, and presents a novel target to treat the underlying disease as well. These findings also demonstrate that ACE-011 has potential as a novel therapy for chemotherapy-induced anemia and may be an effective alternative to EPO-based treatments. To further explore the potential of this novel agent, a phase 2 study investigating ACE-011 in metastatic breast cancer patients with chemotherapy-induced anemia is currently underway.This study was supported in part by a grant from the Multiple Myeloma Research Foundation. Disclosures:Abdulkadyrov:Acceleron: Research Funding. Salogub:Acceleron: Research Funding. Khuazheva:Acceleron: Research Funding. Woolf:Acceleron: Employment, Equity Ownership. Haltom:Acceleron: Employment, Equity Ownership. Borgstein:Acceleron: Employment, Equity Ownership. Knight:Celgene: Employment, Equity Ownership. Renshaw:Celgene: Employment, Equity Ownership. Yang:Acceleron: Employment, Equity Ownership. Sherman:Acceleron: Employment, Equity Ownership.

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.

Use of analysis of iron metabolism with CRP-dependent ferritin index and reticulocyte hemoglobin to determine treatment strategy for chemotherapy-related anemia

e20510 Background: Intravenous iron (IV Fe) can increase the efficacy of erythropoiesis stimulating agents (ESA). However it is still unsettled whether all patients (pts) do so. We conducted a phase II trial to analyze various parameters for the addition of IV Fe to ESA in chemotherapy treated anemic cancer pts. Methods: Pts with an indication for ESA following the EORTC guidelines and a serum ferritin (SF) level ≥20ng/ml were screened in a central laboratory. Those with a C-reactive protein (CRP)-dependent ferritin index (FI = soluble transferrin receptor (sTFR)/log ferritin ratio) above threshold (* FI ≥3.2 if CRP &lt;5mg/l, or FI &gt;2.0 if CRP ≥5 mg/l) were treated with iron only. Those with a sub-threshold FI received Epoetin beta (Epo) 30.000E/wk sc., and from these, those with a reticulocyte hemoglobin (Hb) content (CHr) ≤28pg/ml additionally received Fe-saccharat 200mg/wk iv up to 1g. Results: 11 centers recruited 303 pts (median age 65y, male 41%) from 10/04 to 10/06; 230 (76%) had a sub threshold FI (group Q I+IV), of whom 23 (8%, Q IV) had a CHr ≤28pg. 73 pts (24%) had an increased FI (Q II+III), indicating relative iron deficiency, of whom 27 (9%, Q III) had a CHr ≤28pg. There was no correlation between assignment to one of the groups (Q I-IV) and age, gender, body-mass-index, type or stage of tumor, endogenous Epo level, and hematokrit. In 265 pts evaluable for response Hb on d1 was 9.8 ±1.2 g/dl (mean ± SD) and 10.7 ±1.3 g/dl in 4th week. Mean increase of Hb from d1 to 8th week was 1.4 ± 1.7 g/dl. 36% pts received a transfusion within 12 weeks and 18% after the 4th week. The table shows response according to groups. Conclusions: At study onset we expected nearly all pts to receive Epo and searched for those who might have a benefit from additional IV Fe. However, we conclude in synopsis with other studies, that all pts might have a benefit from IV Fe but only 76%, those with a sub-threshold FI, have a benefit from Epo. [Table: see text] [Table: see text]

Intervention of Iron-folic Acid in School children

Iron and folate deficiency is an important cause of anaemia among young children. Folate is necessary for the production and maintenance of new cells. This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. The aim of this study was to estimate the magnitude of iron deficiency and the improvement in the Hb level by alternate day IFA supplementation. It was observed that amongst 65 students, 63% were found to be anaemic. After alternate day IFA supplementation for 1 month the prevalence decreased to 48.4% with overall increase in mean Hb of 0.59 gm%, from 11.29 to 11.88.

Analysis of Hypochromic Reticulocytes and Ferritin Index as a Rationale for An Effective Therapy of Cancer- and Chemotherapy-Associated Anemia

Introduction: In most cancer patients anemia will be attributable to the mechanisms of chronic disease compounded by the myelotoxic effect of chemotherapy. Nevertheless it is important to exclude alternative explanations such as iron deficiency before starting therapy with erythropoiesis stimulating agents (ESA). Recently Thomas et al. (Clin Chem 2002; 48:1066-76) combined the reticulocyte hemoglobin (Hb) content (CHr) with the C-reactive protein (CRP)-dependent ferritin (Fer) index (FI: soluble transferrin receptor/ log Fer ratio) in a diagnostic plot (DP). We conducted a prospective phase II trial to analyze the diagnostic value of CHr, FI and the DP in anemic chemotherapy treated cancer patients (pts).Methods: Informed consenting pts with an indication for ESA therapy as per EORTC guidelines and a ferritin level ≥20ng/ml were screened with the DP in a central laboratory. DP classifies pts in 1 of 4 quadrants (Q1 – Q4). Those with FI values above threshold (FI ≥3.2 if CRP < 5mg/l, or FI > 2.0 if CRP ≥5 mg/l) were assigned to Q2 (CHr > 28 pg) or Q3 (CHr ≤ 28 pg), and those with sub threshold FI values to Q1 (CHr > 28 pg) or Q4 (CHr ≤ 28 pg). Pts in Q1 received Epoetin beta (Epo) 30.000E/wk sc., those in Q4 additionally Fe-saccharat 200mg/wk iv up to 1g. Pts in Q2 + 3 were treated with oral or iv iron only.Results: 11 centers recruited 303 pts (median age 65 y, male 41%) from 10/04 to 10/06; 230 (76%) had a sub threshold FI (Q1+4), of whom 23 (8%) had a CHr ≤28pg (Q4). 63 pts (21%) fell in Q2+3 with an increased FI, indicating relative iron deficiency, of whom 27 (9%) had a CHr ≤28pg (Q3). There was no correlation between assignment to Q1−4 and age, gender, body-mass-index, type or stage of tumor, measurable metastasis, bonemarrow infiltration, performance status, endogenous epo level, and haematocrit. However, Hb was lower and CRP was higher in Q4. RBC were higher in Q2+3, as leucocytes and thrombocytes were in Q3+4 and transferrin saturation in Q1. In 265 pts. evaluable for response Hb on d1 was 9.8 ± 1.2 g/dl (mean ± SD) and 10.7 ± 1.3 g/dl in 4th week. Mean increase of Hb from d1 to 8th week was 1.4 ± 1.7 g/dl. 36% pts. received a transfusion within 12 weeks and 18% after the 4th week. The table shows response according to Q1−4.Conclusions: Overall response rate was comparable to other ESA studies. However pre therapeutic analysis of hypochromic reticulocytes and ferritin index in the diagnostic plot identifies about a quarter of pts, which were classified in Q2/3 due to elevated FI and had a good response receiving iron only. 8% pts with hypochromic reticulocytes and a sub threshold FI (Q4) had the best Hb-response with epo + iv iron.Table: Response to treatment per quadrant in the diagnostic plotN 265FI < threshold *<threshold*<=?=” ?=”” ??=”/” span=””></threshold*<=?=”>FI ≥ threshold *CHr >28 pg therapy Hb g/dl mean ± SD d1 4thweek Δ Hb 8th wk-d1 mean ± SD median g/dl (Quartile) % pts. with transfusions within 12 weeks after 4th weekQ1 N 194 (73%) Epo only9.9 ± 1 10.7 ± 1.3 1.3 ± 1.5 1.1 (0.3–2.1) 41% 22%Q2 N 31 (12%) Iron only9.6 ± 2 10.4 ± 1.3 1.6 ± 2.4 1.5 (−0.1–2.4) 19% 3%CHr ≤ 28 pg therapy Hb g/dl mean ± SD d1 4thweek ΔHb 8th wk-d1mean ± SD median g/dl (Quartile) % pts. with transfusions within 12 weeks after 4th weekQ4 N 21 (8%) Epo + iv iron9.2 ± 1 10.6 ± 1.4 2.3 ± 2 2.2 (0.3–4.1) 33% 19%Q3 N 19 (7%) Iron only 9.2 ± 1.1 10.9 ± 1.1 1.5 ± 1.5 2 (0.1–2.6) 16% 5%* FI ≥2.0 if CRP <5 mg/l, or FI >3.2 if CRP ≥5 mg/l

Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: A randomized case-controlled study

Background: Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO).Aim of the study: To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy.Patient and methods: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males and 13 females, age; 6.8 ± 2.33 years), or no epoetin alfa (control group = 30 cases, 16 males and 14 females, age; 6.76 ± 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters.Results: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 ± 1.48 g/dl (p < 0.001). An increase in Hb of ≧ 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for ≧ 30 days. The overall response rate (Hb increase ≧ 2 g/dl or Hb ≧ 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-α therapy was found to significantly (p < 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-α was found to be well tolerated.Conclusion: Treatment with QW epoetin-α was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.

Correction of Anemia with Hematide™, a Synthetic Peptide-Based Erythropoiesis Stimulating Agent (ESA), in Oncology Patients Receiving Chemotherapy.

Introduction: Hematide™ a novel, synthetic, PEGylated peptidic compound, binds to and activates the erythropoietin receptor. It is in development for treatment of anemia associated with chronic renal failure and cancer.Objective: To assess the subcutaneous (SC) Hematide™ dose required to increase hemoglobin (Hb) by ≥ 1 g/dL in ≥ 50% of anemic cancer patients (pts) on chemotherapy. Safety, pharmacodynamics and pharmacokinetics were also assessed.Method: In a phase 2, open label, multi-center, dose finding study, up to four doses of Hematide™ were given SC every 3 wks (Q3W) to 4 cohorts of fifteen pts at 0.05, 0.10, 0.15 or 0.2 mg/kg each. Entry criteria included confirmed solid tumor malignancy or lymphoma, >9 weeks of chemotherapy, baseline (BL) H ≥ 8 and <11 g/dL, and adequate iron, folate and B12 stores.Results: Sixty patients were enrolled (45% male). Preliminary data show that across cohorts 0.05, 0.10, 0.15 and 0.20 mg/kg, mean (BL) Hb values were 10.1(±1.07), 10.0(±0.89), 9.8(±0.67), 10.1(±0.69); the % of pts completing the study were approximately 79%, 50%, 60%, and 92%. An increase in mean Hb from BL of ≥ 1g/dL in the pharmacodynamic dataset (forty two pts) at Week 7 occurred in approximately 20%, 70%, 55% and 55% of patients. Three pts withdrew due to AEs and six due to SAEs (none attributed to study drug). Three deaths occurred (two disease progression, one renal insufficiency) none attributed to study drug. One SAE, thrombophlebitis, was considered to be possibly/probably related to study drug. Final safety and efficacy data will be provided at the meeting.Conclusion: In this study, HematideTM dosed SC Q3W resulted in an increase from BL of ≥ 1 g/dL of Hgb in ≥ 50% of patients in the 0.10, 0.15 and 0.20 mg/kg cohorts in the pharmacodynamic analysis. HematideTM appeared to be well tolerated at all doses studied.

Oral Treatment with PBI-1402 Increases Hemoglobin Level and Red Blood Cell Count: A Novel Approach to Treating Chemotherapy-Induced Anemia.

Background: PBI-1402 is a novel orally active low molecular weight synthetic compound with erythropoiesis stimulating activity. Furthermore, a clinical phase I study showed that PBI-1402 induced a significant increase (100%, p < 0.0001, compared to placebo) of relative and absolute reticulocyte count in healthy volunteers after 21 days of oral treatment and was devoid of significant side effects.Outcomes: The objectives of this clinical phase Ib/II trial were to study the safety and tolerability of PBI-1402 and to assess its biological efficacy on hemoglobin (Hb) level and red blood cell (RBC) count in patients with Chemotherapy-Induced Anemia (CIA).Methods: An open label phase Ib/II trial, monitored by a US CRO (Pharm-Olam International), was conducted in patients developing anemia after chemotherapy treatment. Three cohorts of 6 CIA patients received 8 weeks of treatment with PBI-1402 once a day, at different doses, and were monitored every two weeks for safety, tolerability, Hb level, RBC count and blood chemistry. Patients remained on their chemotherapy during PBI-1402 treatment.Results: To date, 12 CIA patients have completed their PBI-1402 treatment. 83% of patients demonstrated a significant increase in RBC (p = 0.015) and 66% in Hb (p = 0.038). Among the responders, the mean Hb increase was 1.1 g/dL (p = 0.0007) from a baseline Hb value of 9.8 g/dL. No patient required a blood transfusion and only one patient had an Hb content below 9 g/dL (8.9 g/dL). PBI-1402 was well tolerated and no significant side effects were observed.Conclusion: PBI-1402, via a mechanism of action distinct from erythropoietin, induced sufficient erythropoiesis to raise the RBC level and Hb in CIA patients. In addition, PBI-1402 is safe and well tolerated. PBI-1402 offers the potential for a novel therapy of the anemia of CIA.

P086 Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: A randomized case-controlled study

Background: Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO). Aim of the study: To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy. Patient and methods: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group 1⁄4 30 cases, 17 males and 13 females, age; 6.8 ^ 2.33 years), or no epoetin alfa (control group 1⁄4 30 cases, 16 males and 14 females, age; 6.76 ^ 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters. Results: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 ^ 1.48 g/dl ( p , 0.001). An increase in Hb of ^ 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for ^ 30 days. The overall response rate (Hb increase ^ 2 g/dl or Hb ^ 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-a therapy was found to significantly (p , 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-a was found to be well tolerated. Conclusion: Treatment with QW epoetin-a was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.