内源性红细胞生成素水平与癌性贫血关系的临床分析

目的:研究分析癌性贫血患者血清促红细胞生成素(erythropoietin,EPO)水平与血红蛋白(Hb)水平之间的关系,指导临床治疗癌性贫血。方法:对135例癌症患者检测血清EPO及血常规,用化学发光免疫分析法检测血清EPO含量,以直线相关分析EPO水平与Hb之间的关系。结果:正常人血清EPO水平为(18.0±7.36)U/L;癌症患者血清EPO中位数(四分数)为26.50(15.9,56.5)U/L;癌症贫血患者血清EPO中位数(四分数)男性为35.7(16.55,74.55)U/L,女性为44.6(17.3,86)U/L。癌性贫血患者组血清EPO水平高于不伴贫血的癌症患者组和正常人群对照组,P=0.000。肿瘤患者血清EPO与同时检验的Hb水平存在负相关性,r=-0.576。癌症贫血患者EPO水平与1周后Hb升高值之间进行直线相关分析,r=0.381,呈正相关。结论:癌性贫血患者血清EPO高于正常人群血清EPO水平,反映机体自身调节功能,监测EPO对于临床应用人rhEPO治疗癌性贫血有指导意义。     

恶性肿瘤患者血清可溶性转铁蛋白受体和促红细胞生成素的研究

[目的]研究恶性肿瘤患者血清可溶性转铁蛋白受体（sTfR）和促红细胞生成素（EPO）的水平及化疗对其影响。[方法]采用酶联免疫吸附法和放射免疫分析法分别测定了85例血液系统肿瘤和79例非造血系统肿瘤贫血患者血清sTfR和EPO水平．并对其中36例急性自血病（AL）和41例初治非造血系统肿瘤患者化疗前后血清sTfR和EPO水平进行比较。[结果]血液系统肿瘤和非造血系统肿瘤患者血清EPO水平均明显高于对照组（P〈0．05）;急性白血病患者化疗后血清sTfR和EPO水平显著高于化疗前（P〈0．05）,初治非造血系统肿瘤患者化疗后血清sTfR和EPO水平与化疗前相比差异无显著性（P〉0.05）,化疗后急性白血病患者血清EPO水平明显高于初治非造血系统肿瘤患者（P〈0．05）。[结论]恶性肿瘤患者体内内源性EPO水平增高．贫血可能不是由于机体EPO产生不足所致：AL患者化疗前后血清ST爪和EPO水平的变化与骨髓红系造血状况有关,可作为临床化疗效果判定的参考指标。     

老年血液系统恶性肿瘤合并贫血患者EPO和sTfR水平的测定及意义

目的 测定老年血液系统恶性肿瘤合并贫血患者红细胞生成素(EPO)、可溶性转铁蛋白受体(sTfR)的水平并对其临床意义进行研究.方法 选取贫血患者142例,根据疾病类型不同将患者分为血液肿瘤贫血组(n=41)、实体肿瘤贫血组(n=51)、缺铁性贫血组(n=50).比较3组患者的血清EPO、sTfR水平,并对EPO、sTfR与血红蛋白(Hb)的相关性进行分析.结果 3组患者的Hb水平比较,差异无统计学意义(P>0.05);血液肿瘤贫血组和缺铁性贫血组患者的EPO水平比较,差异无统计学意义(P>0.05);血液肿瘤贫血组和缺铁性贫血组患者的EPO水平均高于实体肿瘤贫血组(P<0.05);血液肿瘤贫血组和实体肿瘤贫血组患者的sTfR水平均低于缺铁性贫血组(P<0.05);缺铁性贫血组患者的Hb与EPO、sTfR均呈负相关(r=-0.861、-0.546,P<0.01).结论 血液肿瘤患者的贫血机制可能并非源于EPO生成不足,而是由于骨髓红系造血功能受到抑制.     

癌性贫血患者血清促红细胞生成素的检测及其临床意义

促红细胞生成素（erythropoietin，EPO）主要由肾脏近曲小管附近的细胞合成和分泌，是调节红细胞生成和成熟的最重要的细胞因子，而且具有阻止红系祖细胞凋亡的功能。临床上很多癌症患者处于贫血状态，其血清EPO浓度的临床意义究竟如何目前尚有争议。为进一步明确血清EPO水平和癌性贫血水平之间的关系，以指导临床上对这类贫血患者的处理，     

癌性贫血与雄激素及其受体

癌性贫血是影响癌症患者生活质量和预后的重要因素。癌性贫血在实体瘤和血液系恶性肿瘤中的发病率很高,而放化疗进一步加重贫血的发生率和严重程度。癌性贫血的常规治疗方法主要包括输血、红细胞生成刺激因子疗法（如促红细胞生成素EPO）、补充铁剂以及更改放化疗方案。接受大剂量化疗的患者对EPO反应差,雄性激素可能通过改善骨髓对EPO的反应性而发挥疗效,本文综述了癌性贫血的原因,治疗及雄激素治疗贫血的机制。     

重组人红细胞生成素治疗肿瘤相关性贫血的研究

目的:观察促红细胞生成素(EPO)在治疗肿瘤相关性贫血中的疗效和毒副作用。方法:对2007年9月~2007年11月期间我院收治的33例患肿瘤相关性贫血患者使用促红细胞生成素治疗,并观察患者的行为状况、血色素水平以及副反应。结果:33例肿瘤相关性贫血患者在EPO治疗前后的血色素水平有显著升高(88.6g/L±19.3g/L vs 103.5g/L±21.3g/L,P<0.01),EPO治疗后的患者的行为状况评分也有显著性改善。治疗期间有5例患者出现血色素下降,其中输血1例。有9例患者在化疗前或同时使用EPO,血色素由93.7g/L±11.2 g/L升高为100.3g/L±16.8 g/L,P<0.05)。33例患者无血栓形成,血压升高和过敏。结论:促红细胞生成素能提高肿瘤相关性贫血患者的血色素水平和行为状况评分,而且安全性高。EPO可能还有预防化疗导致贫血的作用。     

消化道肿瘤患者红细胞生成素水平的检测及其临床意义

目的 探讨消化道恶性肿瘤患者血清红细胞生成素（EPO）水平的变化,分析 EPO 与贫血和临床病理特征的关系。 方法 用化学免疫发光法检测 226 例 1293 人次的消化道恶性肿瘤患者血清 EPO 水平,分析 EPO 与临床病理特征的相关性。 结果 消化道肿瘤患者红细胞平均血红蛋白浓度（MCHC）为（0.29±0.01） g/L, E P O 水平为（52.25±129.64） IU/L。贫血和 不贫血的肿瘤患者 EPO 有显著性差异（Z=-27.80, P<0.05, 双侧）。不同程度贫血患者的 EPO 有显著性差异（X=126.26, P<0.01, 双侧）。 IV 期患者和其他分期患者 E P O 水平分别为（60.05±141.43） IU/L 和（21.80±28.69） IU/L,有显著性差异 （X=52.47, P<0.01,双侧）, 血红蛋白浓度分别为（122.24±19.66）g/L 和（130.98±16.95）g/L,有显著性差异（X=47.87, P<0.01,双侧）。消化道肿瘤患者化疗前后患者贫血程度及 EPO 水平无显著性差异。 结论 消化道恶性肿瘤贫血多为小细 胞低色素性贫血。贫血肿瘤患者血清 EPO 水平异常增高,且肿瘤晚期和转移患者 EPO 水平增高更明显。分析化疗和贫血 及 EPO 的关系还需要考虑更多相关因素。     

恶性肿瘤患者血清红细胞生成素的水平及化疗对其影响

目的:探讨恶性肿瘤患者血清红细胞生成素(EPO)水平的变化及化疗对其影响。方法:用化学发光法测定了49例血液肿瘤和45例非造血系统肿瘤贫血患者血清EPO水平,与正常对照进行比较,并对其中25例急性白血病和31例非造血系统肿瘤患者化疗前后血清EPO水平进行比较。结果:血液肿瘤和非造血系统肿瘤患者的血清EPO水平均显著高于正常对照组(P<0.001;P<0.01);血液肿瘤患者的血清EPO显著高于非造血肿瘤患者(P<0.001);急性白血病患者化疗后血清EPO水平显著高于化疗前(P<0.001);而非造血系统肿瘤患者化疗前后血清EPO水平无显著差异(P>0.05);HB与血清EPO之间存在显著负相关(r=-0.78,P<0.001)。结论:恶性肿瘤患者体内内源性EPO水平是增高的,化疗后EPO水平的变化与骨髓红系造血状况有关。     

促红细胞生成素在接受化疗的肿瘤患者中的临床应用

 目的 评价促红细胞生成素（epoetin alfa,EPO）对接受化疗的肿瘤患者血红蛋白（hemoglobin,Hb）、输血需求以及生存质量（quality of life,QOL）的影响。方法 将79例Hb≤12.0g/dL的恶性肿瘤患者随机分为两组：治疗组接受EPO8000U/次,皮下注射,每周3次,持续8周（EPO组）;对照组采用最佳支持治疗（best supportive care,BSC）（BSC组）。观察两组化疗期间Hb变化、输血需求、QOL及不良反应情况。结果 在整个治疗过程中EPO组的平均Hb水平保持在12.0g/dL以上,而BSC组的Hb下降。EPO组的Hb反应率为53.8%,明显好于BSC组7.5%（P〈0.0001）。EPO组和BSC组的输血需求分别为7.7%、30%（χ2=6.388,P〈0.05）。8周时,EPO组的FACT-An贫血及乏力平均分数变化分别为（2.16±12.84）、（3.58±10.52）,BSC组分别为（-4.43±13.42）、（-5.34±11.14）（P〈0.0001）。两组的不良反应相似。结论 EPO能使接受化疗的肿瘤患者保持Hb水平、减少输血需求、提高生存质量。     

癌性贫血与雄激素及其受体

癌性贫血是影响癌症患者生活质量和预后的重要因素.癌性贫血在实体瘤和血液系恶性肿瘤中的发病率很高,而放化疗进一步加重贫血的发生率和严重程度.癌性贫血的常规治疗方法主要包括输血、红细胞生成刺激因子疗法(如促红细胞生成素EPO)、补充铁剂以及更改放化疗方案.接受大剂量化疗的患者对EPO反应差,雄性激素可能通过改善骨髓对EPO的反应性而发挥疗效,本文综述了癌性贫血的原因,治疗及雄激素治疗贫血的机制.     

癌性贫血患者内源性促红细胞生成素水平的研究

 目的 研究癌性贫血患者血清促红细胞生成素（ＥＰＯ）水平及其与血红蛋白（Ｈｂ）含量之间的关系。方法 用放射免疫分析检测血清ＥＰＯ含量，以直线相关分析ＥＰＯ水平与Ｈｂ含量之间的关系。结果癌性贫血患者血清ＥＰＯ含量为２．６２±０．９５μｇ／Ｌ（ｎ＝４３），显著高于不伴有贫血的癌症患者（１．７０±０．４１μｇ／Ｌ，ｎ＝３９）和正常对照组（１．５９±０．６９μｇ／Ｌ，ｎ＝９４）。癌性贫血患者血清 ＥＰＯ含量与 Ｈｂ水平存在明显的负相关关系（ｒ＝－０．６８２９３，Ｐ＜０．０１）。结论 癌性贫血患者血清内源性 ＥＰＯ水平增高，提示对此类患者检测血清 ＥＰＯ水平有助于指导临床治疗。     

晚期恶性肿瘤患者的sTfR、TPO与骨髓功能关系的初步报道

目的：观察分析恶性肿瘤患者血中TfR、TPO的表达水平及其作为骨髓功能监测指标的意义。方法：用双单克隆抗体夹心酶联免疫吸附法（ELISA）方法，检测了17例首治的晚期恶性肿瘤患者血中sTfR、TPO水平。结果：2例sTfR升高，1例伴有上消化道大出血，另1例伴有脾功能亢进症；12例sTfR正常，3例减低，肿瘤患者中，12例有贫血。14例患者的血清TPO增高，其中伴有贫血的11例，正常的7例，增高的5例。结论：晚期肿瘤患者多伴有贫血，sTfR未能反馈性增高可能与恶性肿瘤患者存在着骨髓抑制或铁代谢异常有关。TPO水平增高并非仅主要受血小板低下的调节已有报道；本组结果也证实这一结论，TPO血中浓度是否与肿瘤性贫血有关，有待进一步研究。因此结合sTfR与TPO分析方能更全面地反映骨髓功能。     

肿瘤患者化疗相关性贫血的治疗

目的研究我科肿瘤患者贫血的发生情况及化疗相关性贫血的药物干预治疗,及对癌因性疲劳及生活质量的影响。方法收集我科2007年8月～2008年11月肿瘤患者的病例资料,统计贫血的发生率,贫血的程度,与化疗的关系等,对于化疗相关性贫血患者,给予皮下注射重组人红细胞生成素注射液或合并静脉补充铁剂,8周后复查血常规,评价治疗效果并比较治疗前后对癌因性疲劳及生活质量的影响。治疗前后通过患者填写简明疲劳症量表和生活质量测定量表评价治疗前后对癌因性疲劳及生活质量的影响。结果84例肿瘤患者贫血的发生率为83.33%, 其中轻度贫血26人（30.95%),中度贫血26人(30.95%),重度贫血13人(15.48%),危及生命的贫血5人(5.95%),无贫血14人(16.67%),对于化疗相关性贫血患者经治疗后血红蛋白平均升高（21.2±3.3）g/L。皮下注射重组人红细胞生成素注射液合并静脉补充铁剂组血红蛋白增高与单纯皮下注射重组人红细胞生成素注射液组比较有统计学意义。治疗前后疲劳症状量表及生活质量自评量表表明患者癌因性疲劳及生活质量明显改善。结论肿瘤患者合并贫血发生率高,尤其合并化疗者,严重影响患者生活质量,及时发现并纠正化疗相关性贫血能明显改善患者的生存质量,皮下注射重组人红细胞生成素注射液合并静脉补充铁剂能有效改善化疗相关性贫血。     

Predictors of response to erythropoiesis-stimulating agents (ESA) in cancer patients: the role of baseline serum epoetin level

Anemia is the most frequent hematologic abnormality among cancer patients. Its pathophysiology comprises reduction in erythrocyte half-life, poor iron reutilization by the bone marrow, and inadequate response to erythropoietin (EPO), with reduced endogenous EPO (eEPO) levels. Current treatment implies the use of erythropoiesis- stimulating agents (ESA), to which 35-48% of patients show primary resistance. The search for predictors of response to ESA treatment has been inconclusive. Iron or vitamin deficiency, the recent need for transfusion, or a lack of hemoglobin increase within the first 2-4 weeks usually predict resistance to ESA. High serum eEPO levels at treatment initiation (>100-150 mU/ml) may also predict resistance, especially in hematologic malignancies, but the results in solid tumors are not consistent. Although patients with cancer-related anemia show higher eEPO levels than patients without anemia, there is extreme variability among individuals. Future studies are needed to clarify eEPO usefulness in predicting response to ESA treatment.     

The Role of Recombinant Erythropoietin for the Treatment of Anemia in Multiple Myeloma

The key role of a blunted production of endogenous erythropoietin (EPO) in determining anemia of patients with multiple myeloma (MM) has been definitively established. Thus, several clinical trials have investigated the effects of recombinant EPO (r-EPO) in anemic MM patients. The results of these studies have demonstrated that r-EPO is a safe and effective drug, which results in an increase in Hb levels in the majority of treated patients. However, several factors, such as serum levels of endogenous EPO, severity of anemia, presence of normal ery-throid progenitors, serum levels of some cytokines with inhibitory activity on erythroid function and previous treatments, may significantly affect the possibility of response, thereby suggesting the need for careful selection of MM patients for treatment with r-EPO.     

Elevation of soluble transferrin receptor substance in serum of cancer patients with suppressed natural killer activity

Soluble transferrin receptor (sTfR) in serum of cancer patients was measured by a sandwich enzyme-linked immunosorbent assay, and the effect of sTfR for natural killer cytotoxicity was also studied. The statistical values of sTfR levels in sera were found to be 250 +/- 77 U (Mean +/- SD) in healthy individuals, while 288 +/- 162 U in chronic liver disease, 402 +/- 290 U in hepatocellular carcinoma, 429 +/- 261 U in gastric cancer, 347 +/- 207 U in acute leukemia and malignant lymphoma, and 251 +/- 100 U in other cancer. No significant difference in the sTfR levels among the patients was observed, although the difference between the healthy individuals and the patient groups was shown to be statistically significant at p less than 0.01 level. The effect of sTfR isolated from serum of a patient with iron-deficiency anemia by means of Sephadex G-200 column for natural killer activity was carried out. Cytotoxicity of natural killer cell in healthy individuals was inhibited by sTfR as the dose dependent manner, and the inhibitory rate was found to be 23.1 +/- 12.8% (Mean +/- SD) when the concentration of the sTfR was 1,250 U added in the cytotoxicity test. Furthermore, the inhibitory activity of serum in cancer patients was correlated with the sTfR level. These results suggest that sTfR is one of the inhibitory factors for the natural killer cell activity in vivo, and the factor could be facilitated for tumor growth and metastasis. Therefore, the measurement of sTfR in serum may be useful for monitoring immunological competency in cancer patients.     

Treatment of cancer-related anemia with epoetin alfa: a review

Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.     

Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.     

一氧化氮在肿瘤性贫血患者中的表达

目的研究肿瘤性贫血患者血清一氧化氮(NO)和一氧化氮合酶(NOS)的表达水平,探讨其与肿瘤性贫血的关系。方法选择2009年9月至2011年10月期间的肿瘤性贫血患者40例,为观察组;另外选择同期体检的健康人15例,为对照组。采用硝酸还原酶法测定NO和NOS含量。结果肿瘤性贫血患者NO和NOS水平明显高于正常对照(P<0.05);随着贫血程度加重,NO和NOS水平明显升高(P<0.05)。结论 NO在肿瘤性贫血的发病中起重要作用,及早降低NO水平,有助于阻止贫血的发展,可以为肿瘤性贫血的治疗提供新策略。     

Low erythropoietin production as non-oncogenic co-factor contributing to disease-manifestation in low-risk MDS: a hypothesis supported by unique case reports

Little is known about factors contributing to disease-evolution in early-phase myelodysplastic syndromes (MDS). In this article, low erythropoietin (EPO) production is discussed as a 'non-oncogenic' co-factor responsible for disease-manifestation in a group of patients with low-risk MDS. The hypothesis is based on the observations that (i) individuals with bone marrow dysplasia and MDS-related karyotypes but relatively high EPO levels may present without anemia and thus without frank MDS over years, (ii) several elderly patients with idiopathic anemia are low EPO producers and their anemia can be corrected with EPO therapy, and (iii) the well-known fact that low-risk MDS patients typically respond to EPO therapy when they have low endogenous EPO levels.