Clinical significance of serum erythropoietin levels in patients with multiple myeloma]

Serum erythropoietin (Epo) levels were measured in 53 patients with multiple myeloma (MM), 49 normal subjects and 53 patients with some hematological diseases including aplastic anemia (AA), iron deficiency anemia, etc. to study the significance of erythropoietin in anemia of MM. The serum Epo level was 72.0 +/- 94.4 mIU/ml (mean +/- SD) in MM patients, which was significantly higher than in normal subjects (24.1 +/- 6.1 mIU/ml), but lower than in AA patients (7069.9 +/- 9406 mIU/ml). A significant inverse correlation was found between the hemoglobin (Hb) levels and the logarithmic values of serum Epo levels (r = -0.543, p < 0.05) in MM patients. This inverse correlation was stronger (r = -0.636, p < 0.05) in MM patients without renal dysfunction than in whole MM patients, while no correlation was observed in MM patients with renal dysfunction. These results indicate that MM patients with renal dysfunction have a low ability to synthesize Epo and that the supplemental therapy of recombinant Epo is effective to improve their anemia. In addition, the circadian rhythm of serum Epo level was lower in the morning than in the afternoon in both MM patients and normal controls. Serum Epo levels after chemotherapy in MM patients were elevated temporarily and then decreased in spite of no change of blood Hb level.     

老年肿瘤患者血清促红细胞生成素变化及其与化疗的关系

目的 分析老年肿瘤患者血清促红细胞生成素(Epo)水平及其与血红蛋白(Hb)的关系,以及化疗对其的影响. 方法 应用ELISA方法 检测老年肿瘤患者血清Epo,并观察化疗后Epo变化. 结果 (1)老年组Epo为(22.0±15.1)U/L,与对照组(30.4±21.8)U/L比较,差异无统计学意义(t=1.2988,P＞0.05);Epo水平与Hb水平存在负相关关系(r=0.3700,P＜0.01);(2)55例Hb正常者Epo为(14.7±10.6)U/L,22例轻度贫血者(20.2±9.O)U/L,23例中重度贫血者(42.3±24.8)U/L,差异有统计学意义(F=11.6886,P＜0.01);(3)化疗4周期和2周期后,贫血组Epo分别为(45.2±39.1)U/L和(25.8±15.9)U/L,与治疗前的(20.2±10.8)U/L比较,差异有统计学意义(F=4.5477,PG0.01);Hb分别为(96.8±16.6)g/L和(102.1±19.3)g/L,与治疗前的(111.0±20.5)g/L比较,差异有统计学意义(F=4.0071,PG0.01). 结论 老年肿瘤患者与非老年肿瘤患者比较,Epo水平差异无统计学意义;贫血患者Epo水平明显高于无贫血患者;Epo水平与Hb值呈负相关关系;化疗可以引起部分患者发生贫血,并且随着化疗周期的增加,Hb值下降而Epo水平升高.     

New enzyme-linked immunosorbent assay methods for measurement of serum erythropoietin levels and erythropoietin antibodies

For clinical studies with erythropoietin (EPO), enzyme-linked immunosorbent assays for the determination of EPO and EPO antibodies were developed. Using polyclonal and monoclonal EPO antibodies in a sandwich technique, serum EPO levels greater than 10 pg/ml (corresponding to 1 mU/ml, calibrated with the 2nd WHO IRP EPO) can be determined. In 103 healthy blood donors, a mean (+/- SD) value of 36 +/- 19 pg EPO/ml was found. Very high EPO concentrations were found in patients suffering from myelodysplastic syndrome and aplastic anemia; elevated levels were associated with rheumatoid arthritis and myelomatosis. No EPO antibodies were detectable in EPO-treated patients.     

重组人红细胞生成素对维持性血液透析的慢性肾功能衰竭患者血清瘦素水平的影响

目的　探讨重组人红细胞生成素 (rHuEPO)对维持性血液透析 (HD)的慢性肾功能衰竭 (CRF)患者血清瘦素水平的影响及其意义。方法　 80例行HD的CRF患者分为不用rHuEPO治疗组和使用rHuEPO治疗组 ;使用rHuEPO治疗的又分三组 (3个月组 ,6个月组 ,12个月组 )。采用ELISA法测定血清瘦素水平 ,放免法测定血清TNF α水平。结果　使用rHuEPO治疗 6个月后 ,血清瘦素水平明显低于治疗前及未用rHuEPO治疗组 (P <0 .0 5 ) ;血清TNF α、CRP水平也明显低于治疗前及未用rHuEPO治疗组 (P <0 .0 5 )。结论　使用rHuEPO治疗 6个月后血清瘦素水平明显下降     

Lipid levels in serum and cancerous tissues of colorectal cancer patients

AIM: To investigate the correlations between lipid metabolism disorder and the occurrence and development of colorectal cancer by monitoring the alterations in lipid levels in cancerous tissue and serum in patients with colorectal cancer.METHODS: The levels of total and free cholesterol (TCH and FCH), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), apolipoprotein A1 (ApoA-1) and ApoB in serum of 206 patients with colorectal cancer, 70 patients with benign colorectal disease and 300 healthy participants, and in the cancerous tissue and paracancerous tissue of 152 patients with colorectal cancer were measured with an Olympus 600 auto-biochemical analyzer. The obtained data were statistically analyzed.RESULTS: Serum FCH level was significantly higher (1.9 ± 0.4 mmol/L vs 1.3 ± 0.3 mmol/L, 1.9 ± 0.4 mmol/L vs 1.2 ± 0.4 mmol/L, P < 0.05), whereas serum levels of TCH, LDL-C, ApoA-I and ApoB were significantly lower in patients with colorectal cancer than in patients with benign colorectal disease and healthy controls. The levels of FCH and TG in cancerous tissue were significantly lower (14.5 ± 9.6 μmol/g vs 19.3 ± 13.9 μmol/g, P < 0.05; 16.3 ± 19.8 μmol/g vs 44.1 ± 38.1 μmol/g, P < 0.05), whereas HDL-C level was significantly higher (7.9 ± 4.5 μmol/g vs 5.7 ± 3.9 μmol/g, P < 0.01) in cancerous tissue than in paracancerous tissue. The levels of TCH and TG in serum and the levels of TCH and HDL-C in cancerous tissue in patients with colorectal cancer were significantly correlated with TNM stage. The levels of TCH and LDL-C in serum were significantly lower, whereas HDL-C level in cancerous tissue was significantly higher in patients with lymph node metastasis than in patients without lymph node metastasis. The levels of TCH, FCH, TG, HDL-C and LDL-C in cancerous tissue were not significantly different from those in paracancerous tissue. The serum levels of FCH and TG were significantly higher, whereas serum HDL-C levels were significantly lower in patients with rectum cancer than in patients with colon cancer.CONCLUSION: The disordered and abnormally altered levels of lipids in cancerous tissue and serum of patients with colorectal cancer may be correlated with the occurrence and development of colorectal cancer.     

噬血细胞综合征患者血清促红细胞生成素表达水平的研究

目的:探讨血清促红细胞生成素(EPO)在噬血细胞综合征(HPS)患者中的表达水平及临床意义。方法:收集22例HPS患者及15例健康人血清,分别采用酶联免疫吸附(ELISA)方法检测其血清EPO水平,并与各实验室检查指标进行相关性分析。结果:HPS患者组血清EPO水平显著高于健康对照组,差异有统计学意义(P<0.01),感染相关性HPS患者和肿瘤相关性HPS患者血清EPO水平差异无统计学意义(P>0.05)。检测HPS患者血清EPO水平与采血当日红细胞、血红蛋白、血肌酐、尿素氮、三酰甘油、纤维蛋白原、铁蛋白、NK细胞活性、sCD25水平的相关性,发现其与铁蛋白水平呈正相关关系,与其他各项实验室指标均无相关性。结论:HPS患者血清EPO升高可能与贫血、肿瘤有关,但由于炎性因子抑制了EPO对贫血反应的敏感性,所以与血红蛋白之间并无相关关系。EPO在疾病的发生、发展中可能起到一定作用。     

Changes in serum erythropoietin levels during allogeneic bone marrow transplantation

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.     

Evaluation of tumor necrosis factor-alpha and erythropoietin serum levels in B-cell chronic lymphocytic leukemia patients with anemia

Serum levels of tumor necrosis factor-alpha (TNF-alpha) and of erythropoietin (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic leukemia (CLL) in order to determine whether these factors could be significant in the development of anemia, which was observed in some cases with advanced disease. In our series of patients, TNF-alpha serum levels had an inverse correlation with hemoglobin levels (r = -0.813). In patients with anemia, the serum levels of TNF-alpha were significantly higher (p = 0.022) than in those without anemia (186.7 +/- 84.7 vs. 39.8 +/- 20.7 pg/ml). Serum Epo levels were also significantly (p = 0.0003) increased in CLL patients with anemia compared to those without (134.1 +/- 225.9 vs. 12.3 +/- 4.8 mU/ml). The ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia in 70% of patients with anemia and inadequate in the remaining 30%. In the latter, the mean serum TNF-alpha level was significantly higher (p = 0.005) than the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data suggest that although CLL anemia is not characterized by inadequate Epo production, in some CLL patients this factor may be correlated. In these cases, the levels of TNF-alpha were significantly higher than in other anemic cases. Compared to other CLL patients with anemia, these CLL patients might better respond to therapy with recombinant human Epo in pharmacological doses.     

肺癌患者血清内皮抑素的表达及临床意义

目的测定肺癌患者血清内皮抑素水平,探讨其在肺癌的诊断价值及其与化疗的关系。方法应用酶联免疫吸附试验（ELISA法）,测定44例原发性肺癌、20例肺部良陛疾病和20例正常人血清内皮抑素含量。结果（1）肺癌组血清内皮抑素水平（6．33±0．80ng／ml）高于肺部良性病变组（3．91±0．54ng／ml）和正常对照组（3．72±0．58ns／ml）,差异具有显著性（P=0．000,P=0．000）。（2）肺癌患者血清内皮抑素水平与肿瘤组织类型无关（P=0．392）。（3）肺癌患者化疗后血清内皮抑素水平（6．73±0．52ng／ml）高于化疗前（6．09±0．83ng／ml）,差异有统计学意义（P=0．037）。结论肺癌患者血清内皮抑素表达水平明显增高,可作为预测肺癌恶性度和治疗反应的评价指标。     

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (>1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia. Am. J. Hematol. 57:113–118, 1998. © 1998 Wiley-Liss, Inc.     

Endocrine effects of erythropoietin in cancer patients

The recent advances in the knowledge of the psychoneuroimmunological pathogenesis of human neoplasms have demonstrated the existence of feed-back mechanisms operating between interleukins and endocrine secretions, which play an important role in the regulation of the immune responses, including the anticancer immunity. In contrast, few studies only have been performed to investigate the possible relation between endocrine activities and hematopoietic growth factors. The present study was performed to analyze the acute endocrine effects of erythropoietin-alpha (EPO) on the main endocrine secretions. The study was carried out in 10 advanced solid tumor patients. EPO was injected subcutaneously at a dose of 10,000 U, and venous blood samples were collected before and 2, 4 and 6 h after EPO administration. No significant changes in mean serum levels of FSH, LH and TSH were seen in response to EPO. Cortisol and DHEAS concentrations increased after EPO injection, whereas those of PRL decreased, but none of these differences was statistically significant. Finally, mean serum levels of both growth hormone (GH) and somatomedin-C (IGF-1) significantly decreased after EPO administration. This preliminary study shows that EPO may inhibit GH secretion from the pituitary gland and IGF-1 production. Since GH would stimulate EPO release, the results of this study may suggest the existence of feedback mechanism operating between GH secretion and EPO production, with inhibitory effect of EPO on GH secretion, and stimulatory action of GH on EPO production. Therefore, this study would describe the first example of hemato-endocrine feedback mechanisms. Moreover, this study, by showing an inhibitory effect of EPO on IGF-1 secretion, would suggest a possible use of EPO in the medical oncology not only for the treatment of cancer related anemia, but also to counteract tumor growth by blocking IGF-1 production, which has been proven to be a growth factor for several tumor histotypes. Obviously, IGF-1 is not the only tumor growth factor, but it could play a fundamental role in the regulation of production and activity of several other tumor growth factors. In any case, this study describes the only acute endocrine effects of EPO. Therefore, further studies, by evaluating the endocrine effects of a chronic treatment with EPO, will be required to establish which may be its effect on IGF-1 endogenous production, and its consequence on survival time.     

Serum erythropoietin levels in patients with sepsis and septic shock

Abstract: The role of the immune system in the control of the production of erythropoietin is still poorly understood. Herein, the levels of circulating immunoreactive erythropoietin, tumour necrosis factor α, interleukin-1β and interleukin-6 were determined in 10 septic patients for up to 4 d following the admission to an internal intensive care unit. The data show that the production of erythropoietin was not suppressed despite an increase in the levels of proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin level in the nonsurvivors resembled that of acute phase proteins and was independent of the blood haemoglobin concentration. Similar to interleukin 6, abnormally high serum erythropoietin levels appear to be a negative prognostic indicator in patients suffering from septic shock.     

Relationship between serum erythropoietin levels and rT3, T4 concentrations in elderly patients with non-thyroidal illnesses

Thyroid function, plasma erythropoietin and tumor necrosis factor (TNF-alpha) concentrations were measured in 28 elderly patients with chronic non-thyroidal illnesses (NTI) and in 8 healthy subjects as a control group. In the NTI group, the existence of an impairment of thyroid function has been demonstrated in about 85% of the subjects, with a lower T(3) concentration; a low T(3) syndrome with low T(3) levels and high reverse-T(3) (rT(3)) plasma concentrations could be found in 25% of the subjects. A direct correlation between erythropoietin and rT(3) and an inverse correlation between erythropoietin and T(4) were found on NTI patients with endocrine abnormalities.     

Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.