Epoetin delta,erythropoietin produced in a human cell line,in the management of anaemia in predialysis chronic kidney disease patients

ABSTRACT

Objective: To demonstrate safety and efficacy of epoetin delta for the management of anaemia in predialysis patients with chronic kidney disease (CKD).

Research design and methods: This was a multicentre, open-label, uncontrolled study with predialysis CKD patients who had previously received subcutaneous epoetin therapy. Patients were switched to epoetin delta from their previous therapy, at an identical dose. Dose was subsequently titrated to maintain haemoglobin at 10.0–12.0?g/dL. Study duration was 52 weeks.

Main outcome measures: The primary endpoint was average haemoglobin levels over Weeks 12, 16, 20 and 24. Secondary analyses were performed on the proportion of patients with haemoglobin and haematocrit levels over preset target levels, haemoglobin and haematocrit levels through to study end and dosing levels.

Results: Haemoglobin levels were maintained at 11.3 ± 1.2?g/dL over Weeks 12–24. Over 80% of the haemoglobin measurements and 95% of the haematocrit measurements were above the predefined target level (haemoglobin ≥ 10?g/dL; haematocrit ≥ 30%). Weekly dose levels did not change significantly over the course of the trial. Epoetin delta was well tolerated, with adverse events occurring at frequencies expected for this patient population; no patient developed neutralizing anti-erythropoietin antibodies.

Conclusions: Epoetin delta was an effective and well-tolerated agent for the management of anaemia in a subgroup of predialysis CKD patients.     

Screening for Atrophic Gastritis: Comparison of the Results of Azure-A Test and Uropepsin Determination with Gastric Biopsy in a Rural Population

A ‘high risk group’ consisting of 32 persons was selected from 1046 inhabitants of a Finnish rural commune by means of the Azure-A test and uropepsin determination. Gastric biopsy was performed in 24 persons, and the results were compared with those of a representative series of 142 persons ‘selected at random’ from the same population. Significantly more atrophic gastritis was found in the ‘high risk group’ than in the ‘group selected at random’. During two years 2 cases of pernicious anaemia and 2 cases of gastric carcinoma were found in the ‘high risk group’ while in the control group consisting of 1014 persons no case was found.     

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival.     

Weekly intravenous administration of recombinant human erythropoietin in infants with the anaemia of prematurity

To study the safety and efficacy of administering human recombinant erythropoietin (rHuEPO) to infants with anaemia of prematurity, a combined phase I/II trial of weekly intravenous injections for 4 weeks was undertaken. We treated 16 infants with 10, 25, 50, 100 or 200 units/kg body weight in groups of two to four patients per dose level. They were all born prematurely (mean gestational age: 29 weeks; range 27–32), had a mean post-natal age of 42 days (range: 25–59) and haemoglobin concentration of 87 g/l (range: 72–94) when treatment was started. Four patients (25%) needed a transfusion during the trial, one at day 7 treated with 10 units/kg and 3 at days 15, 25, 29 with 100 units/kg. In the others, a progressive rise in mean haemoglobin values was seen in each group after 21 days of treatment, without a dosedependent effect. A positive change in absolute reticulocyte counts with a peak after 7–14 days of therapy was observed with low (25–50 units/kg) but not with higher doses, with a significant difference at day 14 between 25 and 100 units/kg (P<0.01). A dose-limiting severe neutropenia (absolute neutrophil count<0.5×10⁹/l) occurred transiently in five patients, with doses >25 units/kg. No infectious complication and no sign of iron deficiency were observed. Weekly low doses of rHuEPO appear safe, convenient to administer and able to induce a reticulocytic response in infants with anaemia of prematurity. A phase III placebo-controlled trial is needed to confirm these results. Neutropenia associated with rHuEPO administration in infants might be related to their stage of human ontogeny.     

Serum immunoreactive erythropoietin of children in health and disease

Serum immunoreactive erythropoietin (siEPO) was determined in cord serum from neonates (n=97, gestational age 36–43 weeks), in healthy children from birth to adolescence (n=260) and in children with haematological (n=30), renal (n=10) and congenital heart diseases (n=70). In healthy children siEPO levels decreased after birth (geometric mean cord siEPO 35.6 mU/ml with 95% range of 17–56 mU/ml in eutrophic, nondistressed fetuses) and reached lowest values during the first 2 months (geometric mean siEPO 11.5 mU/ml). Thereafter siEPO levels increased slightly and were constant between 2 months and adolescence. The geometric mean siEPO for healthy children after birth was 18.8 mU/ml with 95% range of 7–47 mU/ml. These estimates were not significantly different from normal adult values. In newborns with fetal distress (n=15) cord siEPO was significantly elevated (geometric mean 63.0 mU/ml;P<0.001). In children with haematological disease, siEPO and Hb concentration were inversely correlated (log siEPO (mU/ml)=4.1–0.20×Hb (g/dl);r=–0.62;P<0.0005). This relationship was significantly different in children with chronic renal failure (log siEPO (mU/ml)=0.67+0.035×Hb (g/dl);r=0.50;P=0.1). In children with heart disease the geometric mean siEPO was 19.2 mU/ml with 95% range 8–65 mU/ml for cyanotic (SaO₂<94%) and 17.7 mU/ml with 95% range of 12–36 mU/ml for acyanotic patients. In this group siEPO values were inversely correlated to the arterial oxygen content (log siEPO (mU/ml) =1.61–2.04×oxygen content (l/l);r=–0.28;P<0.02).     

Neocytopheresis: a new approach for the transfusion of patients with thalassaemia major

At present the treatment of thalassaemia major consists of regular blood transfusions coupled with chelation therapy using deferoxamine. A complementary approach to the problem is the use of blood units enriched with young red cells (neocytes), which reduce the transfusional frequency and thereby diminish the risk of iron overload. Young red cell units were collected from blood from 60 volunteer donors using a cell separator (IBM 2997). Donors' blood was anticoagulated and the young red cell harvesting carried out over 4 h at a constant rotor speed of 500 rpm. Three biological criteria were used to evaluate young red cell quality: the number of reticulocytes, the pyruvate kinase activity and the mean corpuscular volume, all of which show an enrichment of young red cells as compared to standard donor units. The ⁵¹Cr young red cell survival in four normal donors and in two splenectomized patients showed an increased red cell half-life compared to the same study performed with standard blood units. Blood consumption was diminished significantly when the two patients were transfused with young red cell units. It must be emphasized that, despite the high cost of this blood product, the efficiency of this transfusion technique, by reducing blood consumption, represents important progress and a hopeful treatment for chronic anaemia.Abbreviations Hb haemoglobin - MCV mean corpuscular volume - PK pyruvate kinase - TQ transfusion quotient - R reticulocytes - ratio reticulocytes/haemoglobin     

Transient erythroblastopenia of childhood

In the period 1975–1983 22 patients, aged 4–36 months were seen with severe transient normochromic, normocytic anaemia caused by a transient erythroblastotopenia.In 20 patients bone marrow aspirations were obtained; they showed erythroblastopenia.In ten cases we observed young lymphoid cells, suggesting a diagnosis of acute lymphoblastic leukaemia. One patient suspected of a leukaemia, was studied in more detail.All patients showed reticulocytopenia. MCV and HbF were within normal range. During recovery reticulocytosis and higher levels of HbF were found. Except for blood transfusion in most patients, therapy (e.g. corticosteroids) was not necesssary. Spontaneous recovery is a feature of this kind of erythroblastopenia, contrasting with congenital hypoplastic anaemia.Abbreviations CHA congenital hypoplastic anaemia - TEC transient erythroblastopenia of childhood - MCV mean corpuscular volume - HbF fetal haemoglobin - ALL acute lymphoblastic leukaemia - cALL common ALL - IgG immunoglobulin G     

905例外来工孕产妇贫血状况调查

①目的评估深圳市部分外来工孕产妇贫血状况。②方法回顾性调查905例外来工产妇，调查内容包括：年龄、孕产次、妊娠期疾病、妊娠期血红蛋白（Hb）、分娩结局等。③结果孕早期、孕中期、孕晚期、产后贫血发病率分别为：20．8％、21.8％、37.2％、44.2％；产后出血和产后贫血的发生率分别为13．4％、96.1％，高于Hb正常组的4.8％、9.0％（P〈0．05）；产前贫血产妇孕周、早产发生率及新生几体重分别是38．3周、10．7％、（2817.9±205.4）g，Hb正常组则分别是39.1周、5．2％、（3211.4±187.9）g，早产发生率比较两组间存在明显差异（P〈0．05）。④结论深圳市部分外来工孕产妇存在较严重的贫血，需引起重视，并给予积极干预。     

Anaemia and depletion of iron stores as risk factors for postpartum depression: a literature review

Purpose: Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD).

Methods: We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies.

Results: Eight out of ten studies found higher risk for PPD (r???0.19 to ?0.43 and ORs 1.70–4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD.

Conclusion: Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.