Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Guía de práctica clínica para el diagnóstico y manejo de la anemia en pacientes con enfermedad renal crónica / Clinical practice guideline for the diagnosis and management of anemia in patients with chronic kidney disease

La Guía de Práctica Clínica (GPC) tratará sobre la el diagnóstico y manejo de la anemia asociada a ERC en el paciente adulto, en el ámbito de todos los niveles de atención, servicios o unidades que presten servicios de a pacientes con Enfermedad Renal Crónica, en lo que corresponda a cada nivel.

Effects of recombinant human erythropoietin on angiogenesis in chronic ischemic porcine myocardium / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium.</p><p><b>METHODS</b>A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis.</p><p><b>RESULTS</b>Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P > 0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023).</p><p><b>CONCLUSIONS</b>rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.</p>

Ephrin B2 is involved in Porphyromonas gingivalis infection-enhanced adhesion of THP-1 to human umbilical vein endothelial cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms of Porphyromonas gingivalis (Pg) infection-mediated enhancement of adhesion between monocytes THP-1 and human umbilical vein endothelial cells (HUVEC) by detecting the effect of erythropoietin producing hepatomocellular receptor interacting protein B2 (Ephrin B2) and its receptors on the adhesion.</p><p><b>METHODS</b>PgATCC33277 was cultured in an anaerobic jar, and THP-1 cells were infected with various concentrations of Pg at multiplicity of infection (MOI) of 1:100 for 8 and 24 h, respectively. The expression of Ephrin B2 receptor of THP-1 cells was detected. After removal of the free Pg, THP-1 cells were cocultured with HUVEC (overexpress of EphrinB2 or not) for 24 h to detect the expression of Ephrin B2 of HUVEC cells after additional cultivation for 23 h.</p><p><b>RESULTS</b>The adhesion of THP-1 cells post infection by Pg to HUVEC was enhanced. The mRNA levels of Ephrin B2 receptors, including EphB3 (5.169±0.152, P = 0.005), EphB4 (11.040±1.195, P = 0.001), and EphA4 (4.976± 0.122, P = 0.001) expressed by THP-1, and Ephrin B2 (8.938±0.962, P = 0.008) expressed by HUVEC were significantly elevated 24 h post infection of Pg. Over expression of Ephrin B2 in HUVEC promoted the adhesion of THP-1 to HUVEC.</p><p><b>CONCLUSIONS</b>Ephrin B2 and its receptors are involved in Pg infection mediated enhancement of the adhesion of THP-1 to HUVEC cells, suggesting that Ephrin B2 participates in the development of atherosclerosis.</p>

Effect of erythropoietin on activities of antioxidant enzymes in the brain tissue of aged rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of erythropoietin (EPO) on the activities of antioxidant enzymes, namely catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissues of aged rats.</p><p><b>METHODS</b>Thirty SD rats were randomly divided into normal control, aging model, and recombinant human erythropoietin (rhEPO) treatment groups (n=10). Morris water maze was used to compare the behavioral indexes. The rats were then sacrificed to observe Nissl bodies in the hippocampal neurons with Nissl staining and test the activities of CAT and GSH-Px in the brain tissues.</p><p><b>RESULTS</b>Compared with the control group, the aging rats showed significantly deteriorated learning and memory abilities (P<0.05), which were improved obviously by rhEPO treatment (P<0.05). The number of Nissl bodies in the neurons was reduced in the aging rats compared with that in the control group, and rhEPO treatment increased the number of Nissle bodies but failed to restore the control level. The aging rats also showed significantly lowered activities of CAT and GSH-Px in the brain tissue (P<0.05), which were increased significantly after rhEPO treatment (P<0.05).</p><p><b>CONCLUSION</b>EPO can enhance the activities of the antioxidant enzymes in the brain tissues of aged rats to increase the antioxidant capacity and produces an anti-aging effect.</p>

Hemoglobin Variability Associated with Different Erythropoiesis Stimulating Agents in Hemodialysis Patients / 대한신장학회지

PURPOSE: This study was undertaken to examine whether differences exist in the hemoglobin variability according to the types of erythropoiesis stimulating agent (ESA) in hemodialysis (HD) patients. METHODS: Clinical data were retrospectively analyzed from 72 patients on maintenance hemodialysis who were using darbepoetin alfa (n=27), epoetin beta (n=27), and epoetin alpha (n=18). As parameters of hemoglobin variability, hemoglobin cycling, the variance of hemoglobin and the SD/mean of hemoglobin were analyzed. Hemoglobin cycling was defined as the presence of cycles with an amplitude >1.5 g/dL and lasting more than 2 months. RESULTS: Hemoglobin cycling was present in 53 (73.6%) out of 72 HD patients. Hemoglobin cycling in patients receiving darbepoetin alfa had greater frequency (1.63+/-0.93 vs. 1.00+/-0.88 times/year, p<0.05), amplitude (2.88+/-1.48 vs. 1.88+/-1.60 g/dL, p<0.05), and velocity (1.21+/-0.74 vs. 0.73+/-0.66 g/dL/month, p<0.05) than that in patients receiving epoetin beta. The variance of hemoglobin in patients receiving epoetin beta (0.79+/-0.53 g/dL) was smaller than that in patients receiving darbepoetin alfa (1.29+/-0.70 g/dL, p<0.05) and epoetin alfa (1.08+/-0.52 g/dL, p<0.05). Also, the ratio of SD/mean of hemoglobin in patients receiving epoetin beta (8.20+/-2.59%) was lower than that in patients receiving darbepoetin alfa (10.81+/-2.10%, p<0.05) and epoetin alfa (10.30+/-2.10%, p<0.05). CONCLUSION: Hemoglobin variability is differential according to various ESAs, and it may be less with epoetin beta compared with darbepoetin alpha and epoetin alpha.

Variação dos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoetina: uma experiência brasileira / Hemoglobin levels in hemodialysis patients treated with epoetin: a Brazilian experience

OBJETIVO: Avaliar a variabilidade dos níveis de hemoglobina (Hb) em pacientes em hemodiálise (HD) tratados com eritropoetina. MÉTODOS: Foram coletados dados retrospectivos de 249 pacientes que estavam em HD e apresentavam, nos três meses anteriores, média de Hb entre 10,5 g/dL e 12,5 g/dL. O período de observação total foi de 36 meses. A cada mês de coleta, classificaram-se os valores de Hb em: < 10,5g/dL, 10,5g/dL< Hb< 12,5g/dL (intervalo alvo), ou Hb >12,5g/dL. Além disto, os pacientes foram divididos em seis categorias de variabilidade da Hb: baixo persistente (<10,5g/dL), alvo persistente (10,5 a 12,5 g/dL), alto persistente (>12,5g/dL), flutuação de baixa amplitude com Hb baixo, flutuações de baixa amplitude com Hb alto e flutuações de alta amplitude. RESULTADOS: Mês a mês, a média da proporção de pacientes com Hb dentro da faixa alvo foi de 50 por cento (variação, 42 por cento a 61 por cento). A proporção de valores de Hb médios acima da faixa alvo (30 por cento) foi mais frequente que a proporção abaixo do alvo (20 por cento). Durante os períodos de seis, 12, e 36 meses, a proporção de pacientes com Hb baixa persistente se reduziu de 3,6 por cento para 0 por cento; de 31,7 por cento para 2,8 por cento naqueles com Hb alta persistente; de 7,6 por cento para 0 por cento naqueles com baixa amplitude com Hb baixo; e de 41,3 por cento para 8,3 por cento nos pacientes com baixa amplitude com Hb alto. Entretanto, houve aumento na proporção de pacientes (de 21,5 por cento a 88,9 por cento) com alta amplitude de Hb. Portanto, à medida que o tempo de observação se alongou observou-se maior variabilidade dos valores de hemoglobina. Nenhum paciente manteve os níveis de Hb dentro do alvo durante todo o período do estudo. CONCLUSÃO: A manutenção da Hb dentro da faixa alvo é difícil, especialmente em períodos longos e a variabilidade ocorre mais frequentemente para valores mais elevados de Hb.

OBJECTIVE: Correction of anemia using epoetin decreases morbidity and increases survival and quality of life in end-stage renal disease. Maintaining hemoglobin levels within the range proposed by guidelines has become a major challenge, with hemoglobin cycling affecting more than 90 percent of patients undergoing hemodialysis. The variability of hemoglobin levels over time was assessed in our patients. METHODS: Data were retrospectively collected on 249 patients undergoing hemodialysis over a 3-year period at seven centers in Brazil. Hemoglobin was measured at least monthly, and target levels were those between 10.5 g/dL and 12.5 g/dL. Patients were grouped into six categories of variability consistently low (<10.5g/dL), consistently target range (10.5 to 12.5 g/dL), consistently high (>12.5g/dL), low amplitude fluctuation with low hemoglobin levels, low amplitude fluctuation with high hemoglobin levels and high amplitude fluctuation. None of the patients maintained stable hemoglobin levels for the entire 36-month period. RESULTS: The mean monthly proportion of patients that had hemoglobin levels within the target range was 50 percent (range, 42 percent to 61 percent). Mean levels above the target (30 percent) were more frequent than those below it (20 percent). During 6, 12, and 36 months, proportions of patients with consistently low levels of hemoglobin decreased from 3.6 percent to 0 percent, from 31.7 percent to 2.8 percent for those with consistently high, from 7.6 percent to 0 percent for those with low amplitude fluctuation with low hemoglobin levels and from 41.3 percent to 8.3 percent for those with low amplitude fluctuation with high hemoglobin levels. However, the proportions of patients with high amplitude fluctuation increased from 21.5 percent to 88.9 percent. CONCLUSION: Maintaining hemoglobin levels within the target range is difficult, especially for longer periods of time. Missing the target seems more often due to ...

Subcutaneous epoetin alfa for anemia in chronic renal failure: A post-marketing surveillance study

OBJECTIVE: This study aimed to assess the safety and effectiveness of subcutaneous (SC) Epoetin alfa in the treatment of Filipino patients with anemia associated with chronic renal failure.METHODS: This is a prospective, observational, multicenter study on chronic renal failure patients with anemia for whom Epoetin alfa SC is indicated. Each patient was followed-up according to the frequency deemed appropriate by the physician for a period of 6 months. Data were collected using a case-report form which is filled-up by the investigator based on available data in the patient records. Patient characteristics were analyzed descriptively. The frequency and description of adverse events were obtained. Baseline and endstudy hemoglobin and hematocrit levels were compared inferentially. Monitoring for antibody-mediated pure red cell aplasia (PRCA) was given special focus.RESULTS: A total of 458 patients were enrolled in the study with an average age 52.8 ± 16.9 years and a slight male predominance (57.8% male). Among patients with primary renal diseases, the most common diagnosis was chronic glumerulonephritis (31.0%), followed by diabetic nephropathy (14.4%) and hypertension (10.0%). Around two-thirds (66.2%) of the patients were on dialysis, while the rest were in the pre-dialysis stage. Most patients had concomitant disease conditions with hypertension (57.9%) and diabetes mellitus (27.1%) being the most common. Most patients also had multiple concomitant medications. Significant improvements inhemoglobin (mean increase 0.8 ± 2.3 mg/dL from 9.66 at baseline; p value at CONCLUSION: Subcutaneously administered Epoetin alfa was effective in significantly increasing hemoglobin and hematocrit in chronic kidney disease patients with anemia. The drug is also safe and well tolerated, with no new safety issue identified, and no incident case of PRCA.

PDpoietin in comparison with eprex in treatment of anemic patients on hemodialysis

PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis. This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex [Janssen Cilag] or PDpoietin [Pooyesh Darou] for 3 months. Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively [P = .002; P = .01]. The mean hemoglobin per cumulative of drug dose index [hemoglobin/[erythropoietin dose/1000 x injections per month]] was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported. Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PDpoietin can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price

Comparison of Erythropoietic Effect between Epoetin-alpha and Darbepoetin-alpha in Hemodialysis Patients: A Randomized Crossover Study / 대한신장학회지

PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of 11.0 g/dL, we stopped ESA. When Hb level decreased to 30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.

Time-averaged Concentration Hemoglobin and Erythropoietin Requirement According to Hemoglobin of Different Session of HD of the Week / 대한신장학회지

PURPOSE: The time average hemoglobin concentration (Hb-Tac) is more likely to represent hemodialysis (HD) patients' true hemoglobin due to variable hemoglobin concentration. This study was performed to evaluate the effect of erythropoietin adjustment on the Hb-Tac according to the Hb of different hemodialysis days. METHODS: A controlled, randomized, cross-over study, where 20 stable hemodialysis patients (7 males, 13 females, mean age 57.8+/-3.0 year, mean HD duration 973+/-707 days) acted as their own controls. EPO adjustment was performed by protocol and according to preHD Hb of the first HD session (group A) or the second HD session (group B) in cross over for each 8 weeks. Serial Hb-tac were calculated by equation [mid week preHD Hb+[midweek pre HT [midweek preHD Hb+(midweek postHD Hb-preHD Hb)/3] every two weeks during the entire study periods. Their iron status were monitored and maintained adequately as K/DOQI guidelines. RESULTS: There was no significant difference in clinical parameters except age during the entire study period. Mean hemoglobin at randomization and after 8, 16 weeks were 10.0+/-0.60, 10.10+/-1.19, 10.1+/-1.03, respectively, in group A compared with 9.93+/-0.62, 9.72+/-1.00, 10.3+/-1.12 g/dL in group B. Mean weekly epoetin alfa dosage at randomization and after 8, 16 weeks were 107.2+/-74.7, 123.2+/-43.1, 123.0+/-85.0 IU/kg/week, respectively in group A compared with 95.4+/-94.7, 107.4+/-60.7, 125.5+/-85.0 IU/kg/week in group B. There were no significant differences in Hb-tac and EPO dosage. Addition of antihypertensive occurred in three patients during EPO adjustment to preHD Hb of the first session. CONCLUSION: EPO dose adjustment according to the different day preHD Hb does not affect the Hb-tac and total EPO.

Hemoglobin response and influence on left ventricular hypertrophy after 24-week treatment of a biosimilar epoetin-alfa in hemodialysis patients with anemia.

BACKGROUND: Anemia is common in end-stage renal disease (ESRD) patients and an important determinant for left ventricular hypertrophy (LVH) in dialysis patients. There are increasing numbers of biosimilar epoetin-alfa entering Thailand. OBJECTIVE: To conduct a prospective trial to evaluate the efficacy and safety of a biosimilar epoetin-alfa (epoetin) (Espogen) in ESRD patients receiving chronic hemodialysis complicated by anemia and to address its impact on the left ventricular mass index (LVMI) and volume index (LVVI) in these patients. MATERIAL AND METHOD: Twenty-two hemodialysis (HD) subjects were recruited from Rajavithi and Huachiew Hospitals. Inclusion criteria were chronic HD, hemoglobin (Hb) < 10 g/dL without preceding treatment (epoetin or transfusion) for 1 month. Echocardiographic baselines were obtained Epoetin-alfa was initially given 4,000 IU subcutaneously twice a week and titrated biweekly to keep the Hb range of 11 to 12 g/dL (titration period 12 weeks). Treatment continued until the end of 24 weeks. Records were made for conventional blood tests, blood pressure, amount of drugs needed to control blood pressure, and adverse events. Echocardiogram was repeated (on observer blinding) at the completion of the present study. RESULTS: After 24-week of epoetin therapy, the predialysis Hb level increased significantly from 8.0 +/- 1.3 g/dL to 11.0 +/- 1.1 g/dL (p < 0.001). The mean dose of epoetin at the present study entry was 143.6 +/- 87.8 IU/kg/ week. At the present study entry, LVH was present in 86.4% of the patients. At the completion of the present study, a decrease in LVMI was observed in 50% of the patients; however, the mean LVMI change was not significantly different. Notably, there were minimal but significant changes in LVEDD (52.8 +/- 7.0 vs. 50.1 +/- 6.9 mm, p < 0.05), LVVI (86.2 +/- 25.2 vs. 75.5 +/- 19.5 mL/m2, p < 0.05) and when subjects were partitioned into tertiles of baseline LVMI, the LVVI change was confined to the highest tertile (103.7 +/- 25.2 vs. 79.6 +/- 21.9 mL/ m2, p < 0.05). The aortic root diameter also significantly decreased despite some increase in blood pressures but without significant change in number of antihypertensive agents. No serious adverse event was observed during the present study period. CONCLUSION: The efficacy of anemia treatment and safety of the biosimilar epoetin-alfa was demonstrated in hemodialysis patients. Significant regression of LVVI and some reduction in LVMI were shown in this 24-week prospective trial.

Antianemic effect of once weekly regimen of epoetin alfa 40,000 units in anemic cancer patients receiving chemotherapy.

BACKGROUND: Anemia is a common problem in the cancer population that is the result of clinical consequences. It also has adverse effects on patients' perceived quality of life. Good management of anemia in the cancer population is therefore essential. A recent published clinical trial has demonstrated statistically significant increases in hemoglobin levels and significantly increased QOL assessment following the administration of recombinant erythropoietin. OBJECTIVE: To evaluate the effectiveness, the safety, and the quality of life by using once weekly dosing of Epoetin alfa (Eprex, Janssen-cilag) 40,000 units in the treatment of anemia in cancer patients receiving chemotherapy. SETTING: Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand. MATERIAL AND METHOD: This was an open label, non-randomized study, in 41 adult male and female anemic cancer patients who had non-myeloid malignancies in the upper area of the body part and hemoglobin ranging from 9-11 g/dL receiving chemotherapy at least 8 weeks with or without concurrent radiotherapy. The subjects were treated with Epoetin alfa 40,000 units once a week subcutaneously. If, the hemoglobin did not increase by > 1.0 g/dl after 4 weeks of treatment, the dose of Epoetin alfa was then increased to 60,000 units per dose subcutaneously at week 5. The Epoetin alfa treatment would continue for a total of 16 weeks. Clinical outcome was evaluated based on quality of life by using the linear analog scale assessment (LASA) and the functional assessment of cancer therapy-anemia (CU-QOL) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases. RESULTS: Seventy six percent of patients receiving Epoetin alfa subcutaneously showed good response with hemoglobin increases of > or = 1 g/dL (Hb level before and after = 9.82 +/- 0.78 g/dL and 12.56 +/- 1.49 g/dL, respectively; p < 0. 001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level and ability to do daily activities evaluated from LASA and fatigue assessed from CU-QOL, were significantly greater (p < 0.01) for week 16 (233.94 +/- 56.01 and 18.45 +/- 13.07) compared to the baseline (202.58 +/- 36.74 and 25.09 +/- 11.00). Epoetin alfa was well tolerated in all patients. CONCLUSION: Once weekly dosing of Epoetin alfa 40,000 units therapy is safe and effective in remodeling anemia and significantly improves the quality of life in cancer patients receiving chemotherapy. Therefore, the physician should maintain hemoglobin concentration of cancer patients in normal level to improve their quality of life through the chemotherapy period.

12-week clinical effects of erythropoietin espogen in end stage renal patients undergoing hemodialysis.

BACKGROUND: Anemia is one of most common complications in end stage renal disease (ESRD) patients. Erythropoietin has been recommended for treatment of anemia in these patients. OBJECTIVES: To evaluate the clinical efficacy, safety and usefulness of newly imported erythropoietin, called Espogen, usage in ESRD undergoing hemodialysis. MATERIAL AND METHOD: An open, non-comparative, prospective study of administered Espogen was conducted in 30 ESRD patients undergoing hemodialysis for a 12 week period. Eligible criteria included hemoglobin of less than 8 g%, hematocrit of less than 25% for at least three consecutive months with a serum ferritin of more than 100 ng%. Initial dose of drug was 150 units/kg/week subcutaneously, two or three times a week and dosage was adjusted to maintain the Hb at 10-12g%. RESULTS: In 28 patients, hemoglobin and hematocrit were increased significantly from 7.1 +/- 1.14 g/dl and 22.1 +/- 3.24% at baseline to 10.1 +/- 1.49 g/dl and 31.7 +/- 4.01% at the end of the study period respectively (p < 0.05). Mean weekly of Espogen dosage was 8390 +/- 2452.7 IU/week, which was 152.1 IU/kg/week. Some patients could reduce the dose at week 10. Reticulocyte increased significantly from 0.69 +/- 0.58% at baseline to highest value, 1.41 +/- 0.74 at 2 week and 1.30 +/- 0.66 at the end of the present study. Serum vitamin B12, serum folate, and red blood cell folate were not significantly changed. However serum ferritin decreased significantly from 840.6 +/- 948.95 to 582.7 +/- 990.70 ng/ml (p < 0.05). General condition including SF-36 score and tiredness were improved. There were no significant adverse events except mean arterial blood pressure of pre dialysis value which was statistically significant increased at the end of the present study (from 101.0 +/- 17.65 at week 0 and 110.4 +/- 16.8 mmHg at week 12, p = 0.0223). CONCLUSION: This clinical study showed that Espogen has proven effective and safe for treatment of anemia in hemodialysis patients. No serious adverse events occurred during the study period.

The Efficacy of Once Weekly Compared with Two or Three Times Weekly Subcutaneous Epoetin Alfa (Espogen(R)) / 대한신장학회지

PURPOSE: Compared with the practice of administrating subcutaneous erythropoietin injection two or three times a week in end-stage renal failure, a weekly administration reduces the frequency of injection and the workload in renal units. We investigated whether subcutaneous epoetin alfa administered weekly was as effective as the same weekly dosage given in two or three divided doses. METHODS: Eighty-three patients were randomized to treatment with subcutaneous epoetin alfa either once a week (n=44), or to their original dosage two or three times a week (control, n=39) for 12 weeks. If hemoglobin was out of range (9.0-12.0 g/dL), the dosage was changed. RESULTS: Mean hemoglobin levels at randomization and after 4, 8 and 12 weeks were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once weekly group compared with 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly epoetin alfa dosage at randomization and after 4, 8 and 12 weeks were 142.8, 123.0, 116.7 and 112.3 IU/kg, respectively, in the once-a-week group compared with 128.4, 119.3, 103.5 and 101.2 IU/kg, respectively, in the control group. No statistically significant differences between the groups were apparent in changes in hemoglobin levels or epoetin alfa dosages at week 12. There was no significant difference between the groups in number of patients who maintained stable hemoglobin levels without epoetin alfa dose increases. CONCLUSION: This study demonstrates that a weekly subcutaneous administration of epoetin alfa is as effective and safe as injecting it two or three times a week administration in maintaining hemoglobin levels in stable hemodialysis patients.

Arteriovenous fistula thrombosis in patients on regular hemodialysis: a report of 171 patients

Fistula thrombosis in patients on maintenance hemodialysis is an important morbidity factor. Arterial or venous thrombotic events have been described as complications in patients on regular hemodialysis. This study was designed to evaluate the risk factors for arteriovenous fistula thrombosis. One hundred and seventy-one patients with arteriovenous fistula on maintenance hemodialysis were studied prospectively during a period of 14 months for any episode of arteriovenous fistula thrombosis, after anticardiolipin antibodies were assayed by ELISA. Other risk factors for thrombosis such as the presence of diabetes or hypertension, the use of erythropoietin [rhEPO], fistula site, gender, age, ultrafiltration, hypotension during dialysis, and the number of dialysis visits in a week were assessed. Fifty-six percent of patients had IgG-anticardiolipin antibodies =/> 10GPL, which was significantly correlated with dialysis duration [23.18 +/- 24.56 months in patients with anticardiolipin antibodies

Efficacy and safety of high dose epoetin alfa therapy in CAPD patients by cross-over study / 대한내과학회지

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an essential and well-established treatment for renal anemia. Rcently, clinicians have moved toward administration of high dose rHuEPO to reduce the inconvenience and time efficient.We aimed to determine whether high dose subcutaneous (SC) epoetin alfa is as efficient and safe as the usual dose for treating anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Twenty-four patients on CAPD were randomly assigned to a high-usual dose group (n=12) and an usual-high dose group (n=12) with a variable interval for 48 weeks. Patients received 10 times treatments by scheduled visiting during Period I lasting 24 weeks and received 4 times treatments by scheduled visiting in Period II lasting 24 weeks by cross-over. The high dose was 10,000 IU and the usual dose was 4,000 IU epoetin alfa regimen. If hematocrit was out of the targeted range, 30~39%, the interval of epoetin alfa was changed within 50% of the previous interval. RESULTS: Fifteen patients, out of 24, completed the study (8 patients in the high-usual dose group; 7 patients in the usual-high dose group). Mean hemoglobin levels at randomization and after 12, 24, 36 and 48 weeks were 10.8+/-1.1, 11.5+/-0.9, 11.5+/-1.5, 11.4+/-1.5, 11.5+/-0.8 g/dL, respectively, in high-usual dose group compared with 11.2+/-0.8, 11.4+/-1.2, 11.2+/-0.9, 11.2+/-1.4, 11.4+/-0.9 g/dL, respectively, in usual-high dose group. The mean weekly epoetin alfa dosages at randomization and after 12, 24, 36 and 48 weeks were 83.6+/-38.1, 87.1+/-35.8, 89.4+/-34.2, 60.1+/-25.1, 62.8+/-30.7 IU/kg/week, respectively, in high-usual dose group compared with 69.8+/-31.6, 64.9+/-12.2, 69.9+/-46.1, 78.8+/-29.3, 75.9+/-16.4 IU/kg/week, respectively, in usual-high dose group. No statistically significant differences between the two groups were apparent for hemoglobin levels or mean weekly epoetin alfa dosages. Treatment interval at Period I and Period II were 13.3+/-5.3, 8.2+/-4.3 days in high-usual dose group compared with 7.0+/-2.5, 13.4+/-4.0 days in usual-high dose group with statistically significant differences. Treatment interval in high dose was about two times as longer as usual dose. Adverse events were generally mild and transient, and pain on injection site following subcutaneous administration was rarely reported. CONCLUSIONS: This study demonstrates that epoetin alfa 10,000 IU is as efficient and safe as 4,000 IU with a similar weekly dose in CAPD patients. Epoetin alfa 10,000 IU administration can reduce frequency of injections by about one half.

Effect of High Dose (10, 000 IU) Epoetin Alfa (Espogen(R)) Therapy in CAPD Patients / 대한신장학회잡지

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an established treatment for renal anemia. We aimed to determine that high dose subcutaneous epoetin alfa is as efficient and safe as usual dose for treating anemia in peritoneal dialysis patient. METHODS: Twenty four patients on CAPD were randomly assigned to either 10, 000 IU (high dose group, n=12) or 4, 000 IU (usual dose group, n=12) epoetin alfa regimen with variable interval for 24 weeks. If hematocrit was out of range (30-39%), the interval was changed within 50% of previous interval. RESULTS: Mean hemoglobin levels at randomization and after 12 weeks and 24 weeks were 11.4+/-1.3, 11.3+/-1.1, and 11.6+/-1.2 g/dL in high dose group compared with 10.8+/-0.8, 11.5+/-1.1, and 10.9+/-1.2 g/dL in usual dose group (p<0.05). The mean weekly epoetin alfa dosages at randomization and after 12 and 24 weeks were 93.2+/-45.3, 95.5+/-33.6, and 102.5+/-43.6 IU/kg in high dose group compared with 78.8+/-29.4, 75.9+/-20.6 and 75.5+/-39.7 IU/kg in usual dose group (p<0.05). But, interval in high dose group was two times as longer as usual dose group. Adverse events were generally mild and transient CONCLUSION: This study demonstrates that epoetin alfa 10, 000 IU is as efficient and safe as 4, 000 IU with similar weekly dose in CAPD patients. epoetin alfa 10, 000 IU administration reduces frequency of injections about one half.

Cancer - related Anemia

Anemia is the most common hematological abnormality in cancer patients, unfortunately, it is often under-recognized and under-treated. The pathogenesis of cancer anemia is complex and most of the time multifactorial; involving factors related to the tumor itself or its therapy. While anemia can present in a wide range of symptoms, involving almost every organ, it is believed that it contributes much to cancer-related fatigue, one of the most common symptoms in cancer patients. In addition, there is increasing evidence to suggest that anemia is an independent factor adversely affecting tumor response and patient survival. While blood transfusion was the only option to treat cancer-related anemia, the use of recombinant human erythropoietin [rHuEPO] is becoming the new standard of care, more so with the recent studies demonstrating the feasibility of a single weekly injection. Things are even getting better with the recent approval of a new form of rHuEPO; Darbepoetin, an analogue with a 3-fold longer half-life. In addition to its effect in raising hemoglobin, several well-controlled studies demonstrated decrease in transfusion requirements and better quality of life assessed objectively using standard assessments scales