Hb Increment Research Articles

Comparison of efficacy of packed red blood cell transfusion based on its hemoglobin content versus the standard transfusion practice in thalassemia major patients (HEMOCON study)

The hemoglobin (Hb) content of packed red blood cell (PRBC) units is heterogenous. The efficacy of a transfusion episode can be assessed if the Hb content of the PRBC is known and the patient’s post-transfusion Hb increment is also determined. This prospective study compared the efficacy of PRBC transfusion based on its Hb content versus the standard transfusion practice. A total of 160 thalassemia major patients were enrolled and randomly divided into two equal groups: Group I (n = 80) – they received ABO/RhD identical PRBCs after determining its Hb content (≥50 g); and Group II (n = 80) – they received randomly selected ABO/RhD identical PRBCs. Hb estimation and a direct antiglobulin test were performed on the post-transfusion sample (1 h). The mean Hb content of the PRBC units was significantly higher (p = 0.000) in group I (67.86 ± 8.07 g; range: 50.80–92.13 g) than group II (60.92 ± 8.29 g; range: 40.86–86.76 g). The mean Hb increment was also significantly higher in group I patients (p = 0.04). In both the groups, there was a significant negative correlation between Hb increment and weight, age, body surface area and blood volume (p < 0.05). There was a significant positive correlation between Hb increment and Hb dose adjusted for body surface area as well as blood volume (p < 0.05). PRBC transfusion was more efficacious in patients who were transfused with PRBCs having a Hb content ≥50 g as compared to those who received randomly selected PRBCs.

1814P - The use of intravenous ferric carboxymaltose without erythropoiesis-stimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy

BackgroundAnemia in cancer patients undergoing chemotherapy is commonly encountered and may worsen their quality of life. Because of recent concerns about their negative effect on overall survival and serious adverse events, erythropoiesis-stimulating agents (ESA) are not commonly prescribed. This study will assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) therapy in such patients. MethodsAdult patients with non-myeloid malignancies on chemotherapy with Hemoglobin (Hb)≤ 11.0g/dL and a life expectancy >24 weeks were recruited. Based on serum ferritin (sFr) level and transferrin saturation (TSAT), patients were categorized into three Groups: Group-I (Absolute Iron Deficiency: AIDA) with sFr <30ng/mL and TSAT <20%. Group-II (Functional Iron Deficiency Anemia: FIDA) with sFr 30-800ng/mL and TSAT <20%. Patients with TSAT >20% were placed in group-III as “others”. Based on Hb level and body weight, patients were given FCM in one or two short intravenous infusions. ResultsA total of 84 patients; 70 (83.3%) females were recruited. Median age [standard deviation] was 53.8 [10.6] years. Chemotherapy varied according to the primary cancer and many had it as a second-line or beyond. The median Hb level at baseline was 10.2 (range: 8.3-11.0 ) gm/dL. At week-12, patients with AIDA (26,31.0%) and FIDA (24, 28.6%) had a significant increment in Hb (median increment: 2.35 and 1.5gm/dL, respectively). Patients in Group-III (34, 40.5%) had limited response. Most of the increment (≥1.0g/dL) occurred as early as week-3. No immediate infusion-related adverse events were reported. However, asymptomatic hypophosphatemia was observed in 39 (46.4%) patients (table).Table1814PTableVariablesAbsolute iron deficiency (n=26)Functional iron deficiency (n=24)Others (n=34)P-valueFerritin Level (week 12, mg/mL) Mean (SD) Median (range)589 (509) 442 (177-2794)838 (875) 577 (168-4184)956 (667) 802 (166-2687)0.0247Phophorus level (week 2, mg/dL) Mean (SD) Median (range)1.8 (0.7) 1.5 (1.1-3.4)2.5 (1.0) 3.3 (1.0-5.4)2.2 (0.9) 3.3 (1.0-4.1)0.0124Hypophophatemia Number Percentage17 65.4%6 25.0%16 47.1% ConclusionsIntravenous FCM, without ESA, is safe and effective in the treatment of anemia in cancer patients undergoing active treatment with chemotherapy. Legal entity responsible for the studyThe authors. FundingKing Hussein Cancer Center. DisclosureAll authors have declared no conflicts of interest.

Recombinant erythropoietin as alternative to red cell transfusion in sickle cell disease.

Disturbances in the physiological regulation of erythropoietin (EPO) in patients with sickle cell disease (SCD) may contribute to worsening anaemia and increased transfusion requirements, but the use of recombinant EPO in this group of patients is controversial. The objective of this study was to evaluate the use of this drug in adult patients with SCD and its effects on haemoglobin levels and transfusion requirements. We conducted a retrospective analysis at the University of Campinas, with nineteen adults with a diagnosis of SCD (HbSS and HbS/β+ thalassaemia), who had received at least 1year of EPO therapy between 2007 and 2014. Haemoglobin concentrations and trends of variation in transfused RBC volumes were compared before and after EPO administration. We observed that seven patients had a good response to treatment (Hb increment higher than 1·5g/dl) and nine had a partial response (0·5-1·5g/dl increment) and there wasa significant decrease in the need for transfusion amongst those who usuallyrequired regular transfusions. There were no increases in the rates of vaso-occlusive crisis or venous thromboembolism in comparison to the year before the onset of the therapy. Erythropoietin therapy led to a marked increase in haemoglobin concentration with a concomitant decrease in the demand for transfusion. Considering all complications related to allogeneic transfusion, we believe that EPO therapy represents an important therapeutic tool in sickle cell anaemia.

Clinical outcome of transfusions with extended red blood cell matching in β-thalassemia patients: A single-center experience

BackgroundThe development of alloantibodies may complicate the management of patients with β-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. Materials and methodsAt the University of Campania “L. Vanvitelli”, we selected β-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. ResultsEighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. ConclusionsThalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.

Newly Diagnosed Pernicious Anemia Can be Treated with a Single Megadose of Cobalamin. Results of a Pilot Trial

Introduction: Pernicious anemia is the leading cause of vitamin B12 deficiency worldwide, caused by an autoimmune reaction against parietal cells in the gastric mucosa leading to B12 absorption impairment. The treatment of pernicious anemia is based on replacement of cobalamin, oral and sublingual routes have been described nevertheless its absorption is erratic. The recommended schedules for vitamin B12 replacement is an intramuscular injection of 1000μg every other day for 1 to 2 weeks followed by weekly injections for a month and then tapered to once a month indefinitely (Green.Blood 2017;129(19):2603-2611). Such an approach can limit treatment adherence for patients in a resource-poor setting and may be unnecessary. Furthermore, the toxicity of cobalamin is minimal, while the benefit of larger doses is unknown.Objective: We aim to demonstrate that a single mega-dose intramuscular (IM) injection of a multivitamin formulation is sufficient to achieve and maintain a complete hematologic response for a six-month period.Methods: We performed a single center pilot study approved by our ethics committee and registered in Clinicaltrials.gov (NCT03372447). All patients with newly diagnosed, untreated pernicious anemia ≥18 years were included after written informed consent was obtained. A single IM dose of a multivitamin formulation consisting on cobalamin 10,000 μg, thiamin 100 mg, and pyridoxine 50 mg was administered. Complete blood count (CBC) was performed at 15 and 30 days and monthly thereafter for a total of six months. Partial response (PR) was considered when Hb ≥10g/dl, Normal WBC, PLT ≥100x103/μL, Complete response (CR) was defined as Hb ≥12g/dl, normal WBC and PLT. Our primary outcome was normalization of CBC (CR) at 6 months. As secondary outcomes we evaluated safety and measured levels of methylmalonic acid (MMA), homocysteine (HCY) and B12 levels (B12L) at diagnosis, three and six months after treatment.Results: Eight patients have been enrolled (5 men and 3 women), median age was 58 years (range 25-77). None had neurological symptoms at presentation. Median laboratory values at diagnosis were Hb 5.9 g/dL (range 3.9-10.7), mean corpuscular volume 113.2 fL (range 94.6-122.9), WBC 2.68x103/μL (range 1.26-6.08), PLT 93x103/μL (range 9.75-156,000), lactic dehydrogenase 3082IU/L (range 439-9840), B12L 85 pg/ml (range 83-90), HCY 154.09 μmol/L (range 83.7-182.44), MMA 24435 nmol/L (range 5175-99500). By day 30 all patients achieved PR. At the end of the third month, 100% of patients reached a CR regarding Hb and WBC while 88% of patients reached a complete PLT response. Median Hb increment at 1 month and 3 months was 6.15g/dl (range 3.1-7.74) and 1.8g/dl (range 0.4-3.7) respectively. The difference between Hb concentration at all time-points was statistically significant (ANOVA; p=0.002) particularly in the first 15 days (p=0.025), while post hoc testing revealed that increments in Hb after the second-week post-treatment were not (p>0.05). Until now, 4/8 patients have completed the primary outcome and all of them have maintained CR and normal levels of HCY and B12L without further cobalamin doses, only one patient had an asymptomatic increase of MMA. No adverse events following the administration of multivitamin preparation were documented.Conclusions: A single dose of a 10,000μg B12 multivitamin was safe and tolerated. Thus far all patients have achieved and maintained a response for at least six months. This simplified single cobalamin administration is an effective option for the treatment of pernicious anemia. [Display omitted] DisclosuresGomez-Almaguer:AbbVie: Consultancy; Novartis: Consultancy.

Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia.

Thalassaemia are the most common inherited autosomal recessive single gene disorders characterized by chronic hereditary haemolytic anaemia due to the absence or reduced synthesis of one or more of the globin chains. Haemoglobin E-β thalassaemia is the genotype responsible for approximately one half of all severe beta-thalassaemia worldwide. This study proposes to evaluate the effect of various molecular parameters on the response of hydroxyurea. Hydroxyurea was started at an initial dose of 10mg/kg of body weight/day on 110 transfusion-dependent HbE-β thalassaemia patients. HbF level was measured by HPLC analysis. β-Thalassaemia mutations, XmnI and five other SNPs, and α-globin gene deletions and triplications were detected by ARMS-PCR, RFLP-PCR and Gap-PCR, respectively. Based on the factors for evaluating hydroxyurea-response, 42 patients were responders as they showed an increment of Hb from a mean baseline value of 6.45g/dl (± 0.70) to 7.78g/dl (± 0.72) post-therapy. Based on increase in HbF above the median value (14.72%) post-therapy, 78 patients were found to be responders. All the 78 responders showed mean decrease in transfusion of 74.26% (± 8.32) with a maximum decrease of 98.43%. There was a significant correlation between decrease in transfusion and increase in HbF level for all 78 responders. XmnI polymorphism showed the strongest association (p < 0.0001) with increase in HbF levels and Hb levels. Patients with α-globin gene deletions were better responders. It was concluded that hydroxyurea treatment is effective in transfusion-dependent HbE-β thalassaemia patients and the response is best in patients having both XmnI polymorphism and α-deletion.

Cytokine profiling and post-transfusion haemoglobin increment in patients with haematological diseases.

In a previous pilot study, we demonstrated significantly lower haemoglobin (Hb) increment after red-blood-cell (RBC) transfusions in febrile patients compared to patients without fever. The aim of this study was to examine associations between inflammatory mediators and post-transfusion haemoglobin increment in patients with haematological diseases. Twenty-seven patients (eight women, 19 men), median age 56 years receiving RBC transfusion, were included in the study. Hb increment per unit transfused was corrected for estimated patient blood volume and the amount of Hb transfused. A wide spectrum of inflammatory mediators was determined by multiplex technology. Association between post-transfusion haemoglobin increment, plasma inflammatory mediators and patient characteristics was analysed using a mixed linear regression model. Febrile patients had significantly lower corrected Hb increment, significantly increased values of IL-6, IL-8, IL-10 and G-CSF, significantly reduced levels of CCL5 and CXCL10, and significantly higher pretransfusion levels of CRP. There was a significant association between pretransfusion CRP levels and corrected Hb increment for the whole patient cohort, but not within each of the two groups. Results demonstrated an association between haemoglobin increment, fever and inflammatory mediators. Febrile patients had a significantly lower corrected Hb increment compared to nonfebrile patients, when adjusting for mediators. When fever was kept constant, a significant negative association between haemoglobin increment and the proinflammatory mediators IL-6 and IL-8 was observed. Both fever and the inflammatory mediators IL-6 and IL-8 were negatively associated with post-transfusion haemoglobin increment.

Intravenous iron administration for post-operative anaemia management after colorectal cancer surgery in clinical practice: a single-centre, retrospective study.

Evidence on the role of intravenous iron (IVI) supplementation after colorectal cancer (CRC) surgery is rather scant. This study was aimed at assessing the benefit of post-operative IVI administration after elective CRC surgery at our institution. This was a single-centre, retrospective observational study including all patients who underwent CRC surgery during 2014. Anaemia was defined as a haemoglobin (Hb) <13 g/dL, regardless of gender. Anaemic patients received 200 mg IVI up to three times a week to cover iron deficiency (IVI group). Those who did not receive IVI were placed on standard care (NIVI group). The primary outcome was the proportion of anaemic patients on post-operative day (POD)1 and POD30. Secondary outcomes included Hb changes from POD1 to POD30, transfusion requirements and complication rates. Of the 159 patients studied, 139 (87%) presented with anaemia: 47 (34%) of these received post-operative IVI and 92 (66%) did not. Patients in the IVI group had lower POD1 Hb levels compared to those in the NIVI group (p=0.001). On POD30, only 103 had their Hb measured (34 IVI, 69 NIVI). Anaemia was more prevalent and more severe among the patients in the IVI group (p=0.027), despite their greater increment in Hb (2.0±1.5 g/dL vs 1.1±1.2 g/dL; p=0.001). Eleven patients needed post-operative transfusions (7 IVI, 4 NIVI; p=0.044). There were no differences in post-operative complication rates between the groups. No IVI-related adverse events were recorded DISCUSSION: Compared with standard care, post-operative IVI administration to anaemic patients improved the recovery of Hb levels at POD30, without increasing post-operative complications.

Baseline Hemoglobin Levels Associated with One-Year Mortality in ST-Segment Elevation Myocardial Infarction Patients.

The association between hemoglobin (Hb) levels and mortality in patients with ST-segment elevation myocardial infarction (STEMI) remains controversial. The purpose of this study was to examine the mortality among STEMI patients with anemia or erythrocytosis, and further establish the relationship between mortality and the increment of Hb level. Between 2006 and 2012, 951 consecutive patients with STEMI undergoing primary percutaneous coronary intervention in a medical center in Northern Taiwan were enrolled in our study, including 535 patients with normal Hb level, 148 with anemia (male Hb ≤ 13 g/dl, female ≤ 12) and 268 with erythrocytosis (male Hb ≥ 16, female ≥ 15). Patients in the anemia group were the oldest, and had higher morbidity than the normal Hb group, followed by the erythrocytosis group. In regression analyses, neither anemia nor erythrocytosis was associated with 30-day and 1-year mortality. Each 1-g/dl increment of Hb level was not associated with 30-day mortality both in patients with anemia or erythrocytosis. However, it was associated with a decreased risk of 1-year mortality in anemic patients [hazard ratio (HR): 0.756, 95% confidence interval (CI): 0.608-0.938, p = 0.011] and an increased risk of 1-year mortality in those with erythrocytosis (HR: 2.086, 95%CI: 1.106-3.937, p = 0.023). In multivariate analysis, each 1-g/dl increment of Hb level was associated with 1-year mortality both in anemic patients and those with erythrocytosis (HR: 0.788, 95%CI: 0.621-0.999, p = 0.049; HR: 2.302, 95%CI: 1.051-5.04, p = 0.037). Higher hemoglobin levels in STEMI patients with anemia were associated with decreased risks of 1-year mortality, whereas higher hemoglobin levels in those with erythrocytosis were associated with increased risks of one-year mortality.

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia.

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.

The influence of free hemoglobin and bilirubin on heparin monitoring by activated partial thromboplastin time and anti-Xa assay.

Elevated free hemoglobin (Hb) and bilirubinemia complicate extracorporeal membrane oxygenation and could affect unfractionated heparin (UH) therapy monitoring by anti-Xa assay and activated partial thromboplastin time (aPTT). To compare in vitro response of anti-Xa and aPTT assays to UH in samples with artificial hyperbilirubinemia and hyperhemoglobinemia and to estimate if this interference is also observed in vivo in pediatric extracorporeal membrane oxygenation. Measurement of aPTT and anti-Xa activity in plasma spiked with UH and increased concentration of free Hb and/or conjugated bilirubin. All samples with anti-Xa activity, antithrombin, free Hb, and bilirubin determination and infused dose of UH from inpatients on extracorporeal membrane oxygenation were extracted from the clinical patient database and analyzed. Each increment of free Hb by 100 mg/dL significantly shortened aPTT, whereas an increment of bilirubin by 6 mg/dL caused significant prolongation of aPTT and stepwise increase of free Hb and/or bilirubin in plasma decreased anti-Xa activity by 0.03 to 0.05 IU/mL. Extracorporeal membrane oxygenation samples with free Hb 50 mg/dL or greater had significantly lower anti-Xa activity compared with normal ones: 0.33 (0.25-0.42) versus 0.4 (0.31-0.48) IU/mL (P = .01), despite the identical UH infusion and similar antithrombin activity. Moderate increase of free Hb by 59 mg/dL was associated with absolute decrease of anti-Xa activity by 0.07 IU/mL. Activated partial thromboplastin time and anti-Xa assay are affected by elevated level of free Hb and/or bilirubin in the presence of UH, and lower anti-Xa activity is noted in extracorporeal membrane oxygenation patients with elevated free Hb. Severe hemolysis and/or hyperbilirubinemia could compromise UH monitoring based on these assays.

HbSD-Punjab

Compound heterozygous HbSD-Punjab is an uncommon hemoglobinopathy encountered in Indians. Limited literature is available about its clinical course. The aim of this study was to describe the clinical and hematological profile of HbSD-Punjab patients from North India. HbSD-Punjab patients diagnosed in the hematology clinics between year 2000 and 2010 were reviewed retrospectively. The diagnosis was established using high-performance liquid chromatography, molecular analysis, and family screening. Clinical details, laboratory parameters, and therapy details were recorded from case records. Ten patients were identified. Median age at onset of symptoms was 3.5 years (interquartile range [IQR], 1.9 to 7.2). Clinical presentation included: anemia in 3, painful vaso-occlusive crisis in 2, acute chest syndrome in 2, and 3 were diagnosed incidentally. All had moderate to severe anemia (mean hemoglobin [Hb]: 6.8 ± 1.2 g/dL). Eight required red cell transfusions (median: 3 [IQR, 2 to 8]). On high-performance liquid chromatography, median HbF, HbD, and HbS were 12.1% (IQR, 9 to 18.3), 39.7% (IQR, 35 to 42), and 38.5% (IQR, 29 to 43). Five patients received hydroxyurea (HDU), median dose: 20 mg/kg/d (IQR, 18 to 23) with median duration of 7 months (IQR; 6, 45). Increment in Hb and reduction in painful crisis was observed in response to HDU. HbSD-Punjab has a heterogeneous clinical presentation. Anemia and sickle crises are quite common. HDU may be considered for those presenting with severe phenotype.

Assessing the Efficacy of RBC Component Transfusion Therapy in Patients with Thalassemia Major

AbstractAbstract 1185 Introduction:Patients with thalassemia major require RBC components that retain sufficient viability to correct anemia and suppress endogenous erythropoiesis. For novel RBC products prepared with pathogen and leukocyte inactivation (PI) it is also important to meet these goals while having minimal effect on transfused iron burden. Unfortunately, ideal endpoints for the efficacy of RBC transfusion in this patient population have not been extensively defined, and published data characterizing relevant statistical parameters are limited. We studied the statistical properties of three transfusion efficacy endpoints in a sample of thalassemia major patients receiving conventional RBC components. The variability of these parameters is a key consideration in the design of clinical trials assessing RBC transfusion efficacy. Methods:Data from 6 transfusion cycles for adult subjects with thalassemia major were randomly extracted from Webthal, a computerized clinical record for thalassemia patients in use at Italian Thalassemia Centers. Only subjects who received all RBC components during a single transfusion episode for each cycle were included in the analysis. Three potential transfusion endpoints were investigated: (1) cumulative hemoglobin (Hb) use (g/kg/day), (2) 1-h post-transfusion Hb increment (g/dL), and (3) proportional Hb decline per day following transfusion (%/day). Data for Hb increment and Hb consumption were based on volume of RBC components adjusted to a hematocrit of 100%. Cumulative Hb consumption provides a summary assessment of transfusion efficacy and iron burden over the 6 transfusion cycles. For the longitudinal endpoints (2) and (3), mixed effects longitudinal models were used to assess whether these endpoints significantly differed across the 6 transfusion cycles. Results:When subjects were selected for consistency of transfusion cycles, and all RBC components for a cycle were administered in a single transfusion episode, a relatively homogeneous population may be defined. In this instance, all of the longitudinal outcome measures were consistent and variability in the measures over 6 transfusion cycles was limited. For 18 subjects over 6 transfusion cycles, the mean cumulative Hb consumption was 0.11 g/kg/day (SD=0.033). Values for each endpoint are presented for each cycle (Table). Conclusions:Based on this analysis, a combination of endpoints related to RBC transfusion for support of thalassemia major can be defined to describe comprehensively the efficacy of novel RBC components. The endpoints presented are clinically relevant to routine care, and thus unlikely to result in missing data. None of the longitudinal endpoints demonstrated substantial differences across the 6 transfusion cycles for patients on a stable transfusion regimen. Thus, these endpoints provide relevant comparative parameters for novel RBC components such as PI RBC. Their limited variability is beneficial for non-inferiority clinical trials. Furthermore, inter-subject variability is much greater than intra-subject variability. A crossover design would further enhance the clinical trial such that a feasible number of subjects may be enrolled to achieve 80–90% power to reject inferiority.ParameterMean ValuesCycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6Estimated 1 hour Hb Increment (g/dL)1 (s.e.)2.73 (0.220)2.59 (0.208)2.53 (0.210)2.49 (0.215)2.54 (0.215)2.53 (0.210)Estimated Proportional Hb Decline (%/day)2 (s.e.)0.84 (0.084)0.80 (0.069)0.72 (0.056)0.77 (0.088)0.84 (0.069)0.76 (0.078)Consumption of Transfused Hb (g/Kg/day)(s.d.)0.11 (0.037)0.11 (0.044)0.10 (0.035)0.12 (0.034)0.11 (0.038)0.11 (0.036)1Covariates added to the model were RBC volume transfused (adjusted to 100% hematocrit) and the number of days within each transfusion cycle.2Covariate added to the model was RBC volume transfused (adjusted to 100 % hematocrit). Two subjects were excluded from this analysis due to outlying values for proportional Hb decline in a single transfusion cycle. Disclosures:Reed:Cerus Corporation: Employment, Stock and stock options Other. Sherman:Cerus Corporation: Employment, stock and stock options Other. Corash:Cerus Corporation: Employment, stock and stock options Other.

Oral iron administration is benefical for anemia with smaller mean corpuscular volume (mcv) in hemodialysis patients with low hepcidin-25 levels

Oral iron administration (OIA) is little benefit, and I.V. iron injection (IVI) is recommended. IVI increases high serum ferritin (ferr) levels, increaseing serum hepcidin-25(hepc) levels, which inhibits intestinal iron absorption. In a state of low hepc levels, intestinal iron absorption can be well preserved. We examined whether smaller or normal MCV affects the therapeutic effect of OIA in HD patients with low hepc levels. Serum hepc were measured in 66 patients on HD. Of these, oral iron was immediately administered in 14 cases who had low serum hepc levels (<14ng/ml). Hb was measured before and 8 weeks after OIA. Serum levels of ferr, hepc, MCV and Hb were measured before starting HD. A correlation between the based MCV and improvement of Hb was analyzed. Mean hepc levels were 14.0± 22.6 ng/mL in 66 cases. Serum levels of hepc correlated with ferr (r=0.46, p<0.01). The values for MCV were less than 88fL in 6 cases (LMCV group, HD duration, 8.7±4.4 years, and the OIA dose, 50 mg/day). The remaining 8 cases showed normal MCV (96.6± 5.7fL) (NMCV group, 7.3±4.6 years, 62.5mg/day). In LMCV group, Hb increased from 9.4±0.4g/dL to 11.2±3.5g/dL. In NMCV group, they increased from 10.3±2.1g/dL to 11.1±2.2g/dL. An increment in Hb was significantly greater in LMCV group (3.1±1.2g/dL, p<0.05) than that in NMCV group (0.8±2.2g/dL). There was no difference between L and N MCV groups in Hb (9.4±0.4, vs. 10.3±2.1 g/dL), and serum levels of ferr (7.8±4.3, vs. 13.9±10.0ng/mL) and hepc (4.6±6.6, vs. 3.7 ± 4.0 ng/ mL). In conclusions, in a state of low hepcidin, OIA is more beneficial for anemia in HD patients with low MCV than in those with normal MCV.

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

A Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week Epoetin Alfa and Every-3-Week Darbepoetin Alfa: A Study of the Mayo Clinic Cancer Research Consortium (MCCRC).

Abstract 3008Poster Board II-984 Introduction:The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (i.e., administration less than once weekly) is a common practice with DA, which is FDA approved for dosing once every 3 weeks (q3wks); a previous study of the North Central Cancer Treatment Group suggested that EA can also be given less often than the FDA-approved once weekly schedule (Steensma DP et al, J Clin Onc 2006; 24:1079). The present study compared 2 different q3wks extended-interval EA regimens with weekly fixed-dose EA and with q3wks DA in pts with CAA. Patients and Methods:Eligible pts were receiving chemotherapy for a non-myeloid malignancy and had Hb <10.5 g/dL, ferritin >20 ng/mL, weight >40 kg and <150 kg, and ECOG performance score £2. Pts were randomized 1:1:1:1 to receive EA 40,000 Units subcutaneously (SC) once weekly (40K arm), EA 80,000 Units SC q3wks (80K arm), EA 120,000 Units SC q3wks (120K arm), or DA 500 mcg SC q3wks (DA arm), for 15 weeks. EA and DA were held for Hb >12 g/dL and restarted at a lower dose when Hb fell to '11.5 g/dL. All pts received ferrous sulfate 325 mg orally once daily, if tolerated. Quality of life (QOL) was measured using the Symptom Distress Scale (SDS), Brief Fatigue Inventory (BFI), FACT-An, and Linear Analogue Self Assessment (LASA) tools. The primary endpoint was the proportion of pts achieving Hb≥11.5 g/dL or increment of Hb>2.0 g/dL from baseline. Secondary endpoints included RBC transfusion requirements, adverse events (AEs), and QOL. Results:239 pts (236 evaluable) enrolled at 10 MCCRC sites between Feb. 2007 and Dec. 2008; 62% of pts completed all study interventions. The median age of enrolled pts was 66 years; 42.4% were men, 91.5% had solid tumors, 26.7% had severe anemia (Hb <9.5 g/dL), and 44.9% were receiving platinum-containing regimens. Baseline characteristics were balanced between study arms, with the exception of gender (39% female for 40K, 60% for 80K, 43% for 120K, 26% for DA). There were no significant differences between treatment arms in the proportion of pts achieving a Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; p>0.41 for all comparisons), but the median Hb increment from baseline was higher in the 40K and DA arms compared to the 2 extended dosing EA arms (40K-2.8 g/dL, 80K-2.0 g/dL, 120K-2.1 g/dL, DA-2.6 g/dL; p=0.005 for 40K vs 80K). Hb response was achieved more quickly in the weekly EA arm, but the difference was not significant (40K-32 days, 80K-50 days, 120K-49 days, DA-49 days; p>0.13). The proportion of patients transfused was similar between arms (40K-27.9%, 80K-33.3%, 120K-22.4%, DA-29.8%; p>0.49). There were no significant differences in QOL changes. Deaths were also similar between arms (40K-5 pts, 80K-7 pts, 120K-7 pts, DA-1 pt, p>0.10) and were primarily due to disease progression. AEs and serious AEs were comparable between study groups; grade 3/4 AEs were observed in 22% of pts in the 40K arm, 22% on 80K, 17% on 120K, and 13% on DA; p>0.56. The median total dose of EA used was highest in the 120K arm (40K-265,000 U; 80K-240,000 U; 120K-360,000 U; p=0.0009 for 40K vs 120K), while pts on the 40K arm were more likely to omit a dose due to a high Hb (40K-63.9% of pts omitted at least one dose; 80K-30.0%; 120K-34.5%; DA-43.6%, p<0.0001 for 40K vs 80K). Conclusion:Although there was no significant difference in the proportion of responding pts (the primary endpoint), Hb increments from baseline were moderately higher with the 2 FDA-approved regimens – weekly EA 40,000 Units, and q3wk DA 500 mcg – than with the extended dosing regimens.This study was supported by a grant from Centocor Ortho Biotech, Inc. to the MCCRC. Disclosures:No relevant conflicts of interest to declare.

A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation On the Erythropoietic Response to Darbepoetin Alfa for Patients with Chemotherapy-Associated Anemia: A Study of the Mayo Clinic Cancer Research Consortium (MCCRC).

Abstract 630 Introduction:Erythropoiesis stimulating agents (ESAs) improve hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with chemotherapy-associated anemia (CAA), but many pts with CAA do not respond to ESAs. Functional iron deficiency due to inflammation-related hepcidin production and pathological sequestration of bioavailable iron may be an important reason for lack of ESA response in iron-replete pts. The common clinical practice of co-administering oral iron with ESAs does not appear to alter the disordered iron processing in CAA. We conducted a prospective trial to evaluate whether parenteral iron might overcome functional iron deficiency and benefit iron-replete pts with CAA undergoing ESA treatment. Patients and Methods:Eligible pts were receiving chemotherapy for a non-myeloid neoplasm and had Hb level <11.0 g/dL, ferritin >20 ng/mL, transferrin saturation <60%, and ECOG performance score ≤2. All pts received darbepoetin alfa (DA) 500 mcg subcutaneously q3wks until Hb reached >11 g/dL, and thereafter DA 300 mcg q3wks; DA was held for Hb >13 g/dL until Hb fell to <12 g/dL, then restarted with 25% dose reduction. Pts were randomized 1:1:1 to receive either sodium ferric gluconate complex in sucrose (Ferrlecit) 187.5 mg intravenously q3wks (total dose 1,125 mg), oral ferrous sulfate 325 mg once daily, or oral placebo. Quality of life (QOL) was measured using the Symptom Distress Scale, Brief Fatigue Inventory, FACT-An, and LASA instruments. The primary endpoint was the proportion of patients achieving Hb ≥12.0 g/dL or ≥2.0 g/dL Hb increment from baseline by the end of the 16-week study. Secondary endpoints included transfusion requirements. changes in QOL, changes in iron parameters, and adverse events (AEs). Results:Planned enrollment was 582 pts, but the study met an early stopping rule due to an excess of serious AEs in the IV iron arm; 502 pts enrolled at 14 MCCRC sites between February 2006 and December 2008. The median age of the 490 evaluable pts was 64 years; 65% were female and 94% white; 6% had hematological neoplasms (lymphoma or multiple myeloma), 25% had severe anemia (Hb <9.5 g/dL), 48% received platinum-containing therapy, and 66% completed all 16 weeks of the study. Baseline characteristics were comparable between groups. With respect to the primary endpoint, 69.5% of IV iron-treated pts achieved a Hb response (median Hb increase from baseline to end of study, 2.7 g/dl), compared to 66.9% with oral iron (median increase, 2.4 g/dL) and 65.0% with placebo (median increase 2.3 g/dl) (p=0.73). There were no significant differences in the proportion of patients requiring RBC transfusion (12.8% for IV iron, 12.9% for oral iron, 13.5% for placebo; p=0.87) or QOL changes. A total of 17 pts (3%) died on study–8 in the IV iron arm, 6 oral iron, 3 placebo (p=0.22). Grade 3 or higher AEs occurred in 54% of IV iron pts compared to 43% for oral iron and 45% placebo (p=0.03). The end-of-study ferritin level was higher in the IV iron arm (median 501 ng/mL) compared to the oral iron (229 ng/mL) and placebo (193 ng/mL) arms (p=0.0022). The median total DA dose administered was similar between arms (p=0.71). Conclusions:Co-administration of DA with intravenous ferrous gluconate q3wks did not result in improvement in Hb levels, reduce transfusions, improve QOL endpoints, or allow lower doses of DA, compared with DA + oral iron or DA + placebo. IV iron increased AEs. The reason for discordant results with 5 previous smaller studies is unclear. Disclosure:The study was supported by a grant from Amgen (Thousand Oaks, CA) to the MCCRC. Disclosures:Off Label Use: Ferrlecit, chemotherapy-associated anemia.

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

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

Determinants of anemia at 1 mo postpartum in Mexican women supplemented during pregnancy

The objective of this analysis was to explore determinants of anemia at 1 mo postpartum (PP) in women supplemented with multiple micronutrients during pregnancy. Data came from a cluster randomized trial where pregnant women received a fortified beverage (FB), tablets (TB) or Sprinkles (SK). Supplements had identical micronutrient content with 15 mg of iron and were delivered daily in the home. Appropriate statistical analyses for cluster randomized trials were used. Mean duration of pregnancy at recruitment was 20.7±5.8 wks, hemoglobin concentration (Hb) at recruitment was 12.1±1.4 g/dL (21.0% anemic, Hb&lt;11 g/dL), and the mean of doses consumed from recruitment to 1 mo post‐partum was 113.8±38.5. At 1 mo PP, 25.9% of women were anemic (Hb&lt;12 g/dL). Factors that were found to be associated with the probability of being anemic include the time since birth of previous child (OR 0.98, p&lt;0.01), Hb at recruitment (OR 0.52, p&lt;0.01), increment of Hb from recruitment to 37 wks pregnancy (OR 0.62, p&lt;0.01), caesarean delivery (OR 1.6, p=0.08) and type of supplement consumed (OR 1.83, p=0.02 for FB and OR 1.66, p=0.06 for SY, respect to TB). A model with the same independent variables explained 22% of variance for Hb concentration at 1 mo PP. In conclusion, despite reasonable compliance with supplementation, the prevalence of anemia at 1 mo PP was high and associated with a number of factors, including the type of supplement consumed.

Should Intravenous Iron Be the Standard of Care in Oncology?

Should Intravenous Iron Be the Standard of Care in Oncology?