Immunosuppressive therapy (IST) is essential to treat aplastic anemia. The pharmacological mechanism, therapeutic effect of main drugs and their application method, reasonable dosage, synergistic action are briefly reviewed in this article. These reviewed drugs include ATG/ALG, CsA, ALG/ATG + CsA, IIST (ALG + CsA) + HGFs, McAb-T, HD-MP and HD-IVIG. The purpose of this review was to direct to clinical therapy for patients with aplastic anemia.
Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; therapeutic use ; Cyclosporine ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Recombinant Proteins

The aim of this study was to investigate the curative effects of amifostine (AMF) combined with recombinant human beta-erythropoietin (rhbeta-EPO) on patients with pure erythroid aplasia (PEA). Two patients with PEA were treated with amifostine and rhbeta-EPO. The therapeutic regimen was adopted with AMF 0.4 g/day given by intravenous injection for 5 days first, then after a break of 2 days it went on for 3 weeks consecutively, that was considered as one treatment cycle. The rhbeta-EPO 6 000 U was used by subcutaneous injection for 3 times per week. The results showed that the red cell count, hemoglobin and reticulocyte count of two patients obviously increased after treatment. The erythroid ratio in bone marrow increased. Bone marrow biopsy showed that the erythroid proliferation improved. Intervals of red cell transfusions (RCT) in the two patients who live by red cell transfusion were prolonged after AMF treatments, and the amounts of each RCT was decreased obviously. The main side effect of amifostine was discomfort of digestive system, but was tolerated by all patients. In conclusion, amifostine plus rhbeta-EPO may be a new, effective and safety method especially for the elder PEA patients. The long-term curative effects and mechanism of amifostine still need further evaluation.
Aged, 80 and over ; Amifostine ; adverse effects ; therapeutic use ; Anemia, Aplastic ; drug therapy ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Humans ; Male ; Recombinant Proteins ; Treatment Outcome

The study was aimed to investigate the curative effects and adverse effects of amifostine in the treatment of patients with myelodysplastic syndrome (MDS). Amifostine (AMF) was used alone (4/12) or combined with recombinant human erythropoietin (rh-EPO) (8/12) in 12 MDS patients. The therapeutic regimen was adopted with AMF 0.4 g/day for 5 days, then took a break of 2 days and then went on for 3 weeks consecutively, that was reputed as one treatment cycle. rh-EPO 6 000 U was used for 3 days per week. The results showed that 12 patients all attained hematological improvement in peripheral blood. 11 cases showed major effective response rate (91.7%), while 1 case showed minor response rate (8.3%). The effective response rate of hemoglobin, leukocytes and platelets was 100%, 75% and 58.3% respectively. The intervals of red cell transfusions (RCT) in 2 cases living on red cell transfusion before AMF treatment were prolonged after AMF treatments, and the amount of each RCT was decreased obviously. The side effect was usually discomfort of digestive system, but all patients can endure. In conclusion, Amifostine is a potential drug in the treatment of MDS patients with safety especially to those elder patients who often suffered from other multiple organ disfunctions, and the curative effect will be improved by more treatment cycles.
Adult ; Aged ; Aged, 80 and over ; Amifostine ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins

The aim of this study was to investigate the curative effect of amifostine (AMF) combined with recombinant human erythropoietin (rhEPO) on the aged patients with myelodysplastic syndrome. Two aged MDS patients (one aged 91; another 86) were treated with amifostine and rhEPO over a period of 4 weeks. The results showed that a short-term curative effect was observed and transfusion interval was prolonged in both patients after 4 week treatment with 5 x 0.4 g AMF plus 3 x 6,000 U rhEPO per week. The reticulocyte count in MDS-RA patient returned to normal at first week of treatment and still remained in normal level for 4 weeks; leukocyte, hemoglobin and platelet values in peripheral blood of MDS-RCMD patient obviousby increased, the abnormally increased reticulocyte value displayed a decrease trend after amifostine plus rh-EPO treatment. In conclusion, amifostine plus rhEPO may have a good therapeutic effect for aged MDS patients, and its clinical long-term curative effect still needs further evaluation.
Aged ; Aged, 80 and over ; Amifostine ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; therapeutic use ; Humans ; Male ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins ; Time Factors ; Treatment Outcome

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (> or =18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb> or =11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481)
Anemia/*drug therapy ; Erythropoietin/*therapeutic use ; Female ; Hemoglobins/analysis ; Humans ; Male ; Middle Aged ; Polyethylene Glycols/*therapeutic use ; Quality of Life ; Recombinant Proteins/therapeutic use ; Renal Dialysis ; Renal Insufficiency, Chronic/*drug therapy ; Republic of Korea

OBJECTIVETo investigate the effect of recombinant human erythropoietin (rhEPO) on the expression of bcl-2 protein in the retina of rabbits with acute high intraocular pressure and explore the mechanism underlying the protective effect of rhEPO on the retina against ischemia-reperfusion injury.

METHODSrhEPO was injected subcutaneously in the ear of a rabbit model of acute high intraocular pressure induced by physiological saline perfusion into the anterior chamber. Bcl-2 protein expression in the retina of the rabbits was observed by immunohistochemical staining on days 1, 3, 7, and 14 after retinal ischemia-reperfusion and compared with that in normal rabbits and untreated rabbit models.

RESULTSbcl-2-positive cells were observed in the retina of normal rabbits with a mean positive cell number of 10.5-/+1.2 in each high-power visual field. Compared with that in the normal control group, the number of the positive cells decreased significantly in both the model group and EPO group (P<0.05, P<0.01), but the latter group showed a significantly greater number than the former (P<0.05 at day 7 and P<0.01 at day 14).

CONCLUSIONSystemic administration of rhEPO can up-regulate the expression of bcl-2 protein in the retina of rabbits with acute high intraocular pressure, which is probably one of the mechanisms for the protective effect of rhEPO on the retina against ischemia-reperfusion injury.

Animals ; Erythropoietin ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Ocular Hypertension ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rabbits ; Random Allocation ; Recombinant Proteins ; Retina ; metabolism

Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.
Anemia, Hemolytic/drug therapy/etiology ; Antiviral Agents/adverse effects/*therapeutic use ; Erythropoietin/therapeutic use ; Hepatitis C, Chronic/*drug therapy ; Humans ; Individualized Medicine ; Interferon-alpha/adverse effects/therapeutic use ; Polyethylene Glycols/adverse effects/therapeutic use ; Protease Inhibitors/therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/adverse effects/therapeutic use ; Ribavirin/adverse effects/therapeutic use

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.
Adult ; Anemia/drug therapy/etiology ; Antibodies/*blood/immunology ; Bone Marrow Cells/pathology ; Drug Hypersensitivity/immunology ; Erythropoietin/*analogs & derivatives/therapeutic use ; Erythropoietin, Recombinant/adverse effects/*immunology/therapeutic use ; Female ; Glomerulonephritis, IGA/complications ; Hematinics/adverse effects/immunology/*therapeutic use ; Humans ; Kidney Failure, Chronic/complications ; Oxymetholone/therapeutic use ; Red-Cell Aplasia, Pure/chemically induced/*drug therapy/immunology

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin < or =15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of > or =3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4+/-1.1 vs 14.2+/-1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781).
Acute Disease ; Adult ; Altitude Sickness/diagnosis/epidemiology/*prevention & control ; Blood Pressure/physiology ; Drug Administration Schedule ; Erythropoietin/*therapeutic use ; Female ; Headache/physiopathology ; Hemoglobins/analysis ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Oxygen/blood ; Questionnaires ; Recombinant Proteins/therapeutic use

OBJECTIVETo study the effect of treatment of renal anemia by combination of Bushen Jianpi Recipe (BJR, a Chinese experience recipe for supplementing Shen and supporting Pi) and low dosage erythropoietin (EPO), and the influence of treatment on change of serum tumor necrosis factor alpha (TNF-alpha) so as to explore the possible mechanism of integrative Chinese and western medicine (ICWM) in treating renal anemia.

METHODSPatients with renal anemia were randomly divided into two groups, the ICWM group and the control group, symptomatic and supporting treatment such as dialysis, supplementing of ferrous, foliac acid and vitamin B12, was given to both groups. Additionally, to the ICWM group, 50 IU/kg of EPO subcutaneous injection for twice every week, and oral intake of BJR, one dose per day taken in two parts, were given, and to the control group, EPO alone, 50 IU/kg by subcutaneous injecting, 3 times per week, was given. The therapeutic course for two groups was 3 months. Blood levels of hemoglobin (Hb), hematocrit (Hct), TNF-alpha were measured before treatment and the therapeutic effect was observed.

RESULTSAfter treatment, the levels of Hb and Hct increased significantly in both groups (P < 0.01), comparison between the two groups in Hb and Hct after being treated for 3 months showed significant difference (P < 0.05). The serum level of TNF-alpha was markedly higher than normal range in both groups before treatment, it significantly lowered after treatment in the ICWM group (P < 0.05), but unchanged in the control group.

CONCLUSIONCombination of BJR and EPO could significantly inhibit the production of TNF-alpha, this may be an important factor for ICWM in effectively improving sensitivity to EPO.

Adult ; Anemia ; blood ; drug therapy ; etiology ; Chronic Disease ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Erythropoiesis ; drug effects ; Erythropoietin ; therapeutic use ; Female ; Glomerulonephritis ; blood ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Recombinant Proteins ; Tumor Necrosis Factor-alpha ; metabolism