Effective Treatment Of Anemia Research Articles

Tratamiento con eritropoyetina en niños críticamente enfermos

To analyze whether erythropoietin treatment increases hemoglobin and decreases transfusion requirements in critically ill children. We performed an observational, prospective study of 23 critically ill children aged between 1 month and 6 years. Recombinant human eritropoietin (rHuEPO) was administered at a dosage of 150-750 U/kg/week over 3 days. Hemogram, reticulocyte, iron metabolism, serum ferritin and transferrin were measured before treatment started and weekly thereafter. After erythropoietin treatment, hematocrit, hemoglobin and red blood cells progressively increased, with a maximal response in the sixth week. At the end of treatment, hemoglobin increased 1.68 g/dl, hematocrit by 5 % and erythrocytes 600,000/ml/mm3. Transfusion requirements decreased from 59 transfusions at baseline to 12 in the first week of treatment and none from the sixth week. No treatment-related adverse effects were observed. Erythropoietin can be an effective treatment for anemia in some critically ill children, decreasing the number of transfusions and increasing hemoglobin.

Baseline and early treatment factors are not clinically useful for predicting individual response to erythropoietin in anemic cancer patients.

Recombinant human erythropoietin (rHuEPO) is an effective treatment for anemia in patients with cancer, and recent studies show that over two-thirds of patients can be expected to respond with a large increase (>2 g/dl) in hemoglobin concentration. However, it would be helpful to identify likely responders and nonresponders before initiating treatment. Previous studies have suggested that high pretreatment endogenous erythropoietin levels are associated with a lower response to erythropoietin, especially in certain patient groups, such as patients with hematological malignancies, non-chemotherapy patients, or patients with myelodysplastic syndrome. Various algorithms have therefore been developed to predict patient response to rHuEPO using baseline serum erythropoietin levels and other baseline factors. We performed an analysis of data pooled from four randomized clinical trials of 604 patients with non-myeloid malignancies, examining the clinical usefulness of pretreatment and early treatment factors for predicting response to erythropoietin. The analysis confirms several other reports that the most predictive models combined pretreatment and early treatment factors, including change in hemoglobin at 4 weeks, but even these models did not increase sensitivity above 85% (total response in unselected patients was 68.1%), while specificity remained poor. We conclude that clinically useful prediction of response to erythropoietin is not possible using baseline or early response variables because of poor sensitivity and specificity of prediction compared with generally accepted clinical tests.

Erythropoietin Treatment in Metastatic Breast Cancer

Erythropoietin is an effective treatment for anemia in patients with various types of cancers, but few studies have evaluated the benefit of treatment in advanced breast cancer. In this multicenter study, we investigated the influence of two different doses of epoetin-beta on the level of hemoglobin, the need for blood transfusion, quality of life and safety aspects in patients with metastatic breast cancer. A total of 180 patients were randomized to receive either 1000 IE or 5000 IE epoetin-beta subcutaneously three times per week for 24 weeks. An increase of 20 g/L was defined as a positive hemoglobin response. Blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were recorded. Quality of life was measured with the aid of the EORTC QLQ-C30 questionnaire. Hemoglobin levels increased significantly in both groups. In the high-dose group, the initial mean Hb value was 98 g/L (64-110), which increased to 121 g/L (83-165) by week 24. In the low-dose group, the mean Hb value was 99 g/L (77-110.5) and by week 24 it was 116 g/L (81-144). The majority of patients who responded to treatment did so during the first four weeks. After 4 weeks, 7 patients in the low-dose group and 24 patients in the high-dose group had increased their Hb values by more than 20 g/L. The need for transfusion was low and did not differ between the groups. Quality of life was significantly enhanced in both groups, and there was no difference in the global quality of life between the two study arms. Epoetin-beta is a well-tolerated, safe and effective treatment of anemia in patients with metastatic breast cancer. There were significant improvements in Hb levels and quality of life in both groups.

Erythropoietin Treatment in Metastatic Breast Cancer

Erythropoietin is an effective treatment for anemia in patients with various types of cancers, but few studies have evaluated the benefit of treatment in advanced breast cancer. In this multicenter study, we investigated the influence of two different doses of epoetin-beta on the level of hemoglobin, the need for blood transfusion, quality of life and safety aspects in patients with metastatic breast cancer. A total of 180 patients were randomized to receive either 1000 IE or 5000 IE epoetin-beta subcutaneously three times per week for 24 weeks. An increase of 20 g/L was defined as a positive hemoglobin response. Blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were recorded. Quality of life was measured with the aid of the EORTC QLQ-C30 questionnaire. Hemoglobin levels increased significantly in both groups. In the high-dose group, the initial mean Hb value was 98 g/L (64-110), which increased to 121 g/L (83-165) by week 24. In the low-dose group, the mean Hb value was 99 g/L (77-110.5) and by week 24 it was 116 g/L (81-144). The majority of patients who responded to treatment did so during the first four weeks. After 4 weeks, 7 patients in the low-dose group and 24 patients in the high-dose group had increased their Hb values by more than 20 g/L. The need for transfusion was low and did not differ between the groups. Quality of life was significantly enhanced in both groups, and there was no difference in the global quality of life between the two study arms. Epoetin-beta is a well-tolerated, safe and effective treatment of anemia in patients with metastatic breast cancer. There were significant improvements in Hb levels and quality of life in both groups.

Quality of life benefits of early anaemia treatment

In evaluating outcomes in end-stage renal disease (ESRD), quality of life has become as important as morbidity and mortality. Various instruments are available to analyse patients' perceptions of the physical, psychological and social domains of health. Non-specific instruments, such as the Sickness Impact Profile, the Karnofsky Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), have been widely used in evaluating quality of life in various chronic diseases including ESRD. The Kidney Disease Quality of Life (KDQOL) questionnaire and other scales have also have been developed specifically for ESRD patients. Several studies have demonstrated a significant improvement in quality of life after initiation of epoetin treatment in both dialysis patients and those with early renal failure. Quality-of-life scores show a strong positive correlation with haemoglobin concentration. Other factors associated with better quality of life are higher socio-economic level and level of education. However, older age, comorbidity, diabetes, female sex, and unemployment have a negative influence on quality of life. In patients not yet on dialysis, quality of life deteriorates as the glomerular filtration rate decreases. The later the patient is referred to a nephrologist, the worse the quality of life. Recent studies show that quality of life is a prognostic factor for survival. Early and effective treatment of anaemia in ESRD patients is essential in maintaining quality of life both before and after initiation of dialysis.

The evaluation of iron status in hemodialysis patients.

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.

Epoetin beta. A review of its pharmacological properties and clinical use in the management of anaemia associated with chronic renal failure.

Epoetin beta is a recombinant form of erythropoietin, the hormone responsible for the maintenance of erythropoiesis. The drug binds to and activates receptors on erythroid progenitor cells which then develop into mature erythrocytes. Epoetin beta increases reticulocyte counts, haemoglobin levels and haematocrit in a dose-proportional manner. These changes are accompanied by beneficial cardiovascular effects, including decreased cardiac output, resting heart rate and left ventricular hypertrophy in patients with chronic renal failure (CRF). Increases of 15 to 54% in haemoglobin levels and 17 to 60% in haematocrit were reported after subcutaneous or intravenous epoetin beta therapy in studies of 8 weeks' to 12 months' duration. Two multicentre clinical trials demonstrated clearly the superior efficacy of epoetin beta over placebo in 229 patients with CRF undergoing haemodialysis. Reduction or elimination of transfusion requirements was reported in studies where this parameter was measured. Comparative data indicate that dosage reductions of approximately 30% compared with intravenous therapy are possible when subcutaneous administration of epoetin beta is used. Haematocrit increased more rapidly in 5 multicentre studies in patients who received epoetin beta subcutaneously than in those who received the same dosage intravenously. Correction of anaemia with epoetin beta is associated with significant improvements in quality of life in patients with CRF. Available data indicate greatest cost-effectiveness in patients who are severely incapacitated by anaemia before treatment. The cost of administration of the drug may also be reduced by the use of the subcutaneous route. Hypertension may occur in patients who receive epoetin beta but may be minimised by avoiding rapid increases in haematocrit (> 0.5%/week), and is managed in most cases with control of fluid status and antihypertensive medication. Although clotting of the vascular access has not been conclusively linked to epoetin beta, caution is recommended in patients undergoing haemodialysis. Increased heparinisation is recommended to prevent clotting in dialysis equipment. Epoetin beta is more effective and/or better tolerated than alternative treatments (e.g. androgenic steroids) for anaemia associated with CRF. It also causes significant improvements in quality of life, exercise capacity and overall well-being. Results of clinical studies indicate that subcutaneous administration is desirable where possible in the majority of patients. Thus, epoetin beta has become established as an effective treatment for anaemia associated with CRF.

Subcutaneous recombinant human erythropoietin for the treatment of anemia in myelodysplastic syndromes.

Recombinant human erythropoietin (rhEPO) was administered subcutaneously to 13 anemic (Hb < 10 g/dl) patients with myelodysplasia (MDS). rhEPO was given 3 times a week at doses of 75-250 U/kg body weight, over a maximum period of 24 weeks. Five patients (38%) showed a response to rhEPO treatment. rhEPO was well tolerated and without relevant side effects throughout the study. All responding patients had low but detectable pretreatment circulating erythroid progenitor cells (BFU-E) and the response to rhEPO was associated with a significant increase in BFU-E (p < 0.01); concentrations of serum transferrin receptor (TfR) also consistently rose in all responding patients. Baseline erythropoietin (EPO) concentrations did not significantly differ between responders and nonresponders, although 4 out of the 5 responders had relatively low levels of EPO. In conclusion, subcutaneous rhEPO administration appears to be an effective treatment of anemia in a substantial subset of patients with MDS. Relatively low baseline EPO concentrations, detectable pretreatment circulating BFU-E and an early increase in the serum concentrations of TfR seem to be criteria for predicting response to rhEPO in patients with MDS.

Biology and pharmacology of hematopoietic growth factors.

Several glycoproteins that control blood formation have recently been characterized. Through their overlapping, synergizing, and antagonistic effects, they regulate hematopoiesis in a highly differentiated network. Large scale production of these colony stimulating factors (CSFs) has been made available by recombinant DNA technology, and a series of clinical studies in a variety of indications has been finished. In general, the subcutaneous application seems to be superior to the intravenous injection and causes less toxicity. Erythropoietin has been shown to be a highly effective treatment for anemia in patients with chronic renal failure. Granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor are capable of ameloriating the chemotherapy induced neutropenia, and to abbreviate the time span of myeloaplasia after bone marrow transplantation. The potentials of other colony stimulating factors like Interleukin 1 and Interleukin 3, and combination regimens of several CSFs will be discussed.

Stepwise Correction of Anaemia by Subcutaneous Administration of Human Recombinant Erythropoietin in Patients with Chronic Renal Failure Maintained by Continuous Ambulatory Peritoneal Dialysis

Sixteen anaemic CAPD patients (Hb less than 9 g/dl) were treated with thrice-weekly subcutaneous recombinant erythropoietin, epoetin-alfa. The dose was adjusted to induce a stepwise increase in haemoglobin. Fourteen patients reached a first target haemoglobin of 11.0-11.5 g/dl and eight of these a second of 13.0-13.5 g/dl, but one could not be maintained at this level. Failure to reach or maintain the second target in nine subjects was accounted for by incomplete responses associated with infection in one, extreme shortening of red-cell survival in another, and was unexplained in one subject. These three received the maximum dose studied of 450 IU/kg per week. Six other subjects were withdrawn from the study for reasons unrelated to treatment with erythropoietin. The median dose required to maintain the haemoglobin at 11.0-11.5 g/dl was 75 IU/kg per week and at 13.0-13.5 g/dl was 150 IU/kg per week. Quality of life, assessed in 12 patients at haemoglobin 11.0-11.5 g/dl, showed significant improvement in energy, and at 13.0-13.5 g/dl improvements in sleep and emotional wellbeing became significant. Twelve subjects required either institution of, or an increase in, treatment for hypertension. The thrice-weekly subcutaneous doses of erythropoietin were well tolerated and were a convenient and effective treatment for anaemia in patients on CAPD.