肿瘤相关性贫血的治疗

肿瘤相关性贫血是肿瘤相关性炎症或肿瘤相关治疗导致骨髓抑制（主要是放、化疗）引起的贫血。肿瘤相关性 贫血可以发生在肿瘤诊治的任何阶段，其发生与肿瘤类型、分期及治疗等因素密切相关。2012 年国内的调查显示，肿瘤相 关性贫血的发生率为60.83%，其中轻度贫血40.84%，中度贫血15.67%，重度贫血3.47%，极重度贫血0.84%。发病率较高的肿瘤分别为消化道癌、乳腺癌和肺癌等。研究显示，肿瘤相关性贫血会明显降低肿瘤患者的生活质量，影响治疗效果， 缩短生存期，增加死亡风险；而通过合理的治疗，纠正贫血后，可以改善患者的生活质量，提高生存率。肿瘤相关性贫血 的发病机制复杂，可能与肿瘤本身及其并发症（如肿瘤侵犯骨髓、溶血、失血、肿瘤相关性炎症等）、治疗手段引起的骨 髓抑制（化疗、放疗等）等有关。肿瘤相关性贫血的治疗目标为“提高生活质量，降低红细胞输注需求”。在病因治疗的 基础上，补充造血原料（铁剂、叶酸、维生素 B12 等），应用促红细胞生成素类药物及输红细胞治疗为其常用治疗手段。     

促红细胞生成素治疗肿瘤相关性贫血的研究进展

摘 要：贫血是恶性肿瘤常见的伴随疾病。肿瘤相关性贫血对患者存在较大的影响,可以降低患者生活质量、影响放化疗疗效等。促红细胞生成素（erythropoietin,EPO）是临床上治疗肿瘤相关性贫血的重要方式,其可提高患者血红蛋白水平、减少红细胞的输注、改善生活质量,但是使用EPO可以使血栓发生风险升高,关于是否影响患者总生存期、促进肿瘤转移等方面仍然存在争议。文章根据国内外相关文献,对EPO用于肿瘤相关性贫血患者的疗效及安全性进行总结。     

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。     

肿瘤相关性贫血的研究进展

肿瘤相关性贫血是影响患者预后和生活质量的重要因素,在肿瘤患者及综合治疗中贫血的发生率很高。在肿瘤相关性贫血的治疗中,促红细胞生成素EPO治疗肿瘤相关性贫血的研究是目前最活跃的方法之一。然而EPO治疗的安全性问题一直是争论的焦点。     

肿瘤相关性贫血的研究进展

肿瘤相关性贫血是影响患者预后和生活质量的重要因素,在肿瘤患者及综合治疗中贫血的发生率很高。在肿瘤相关性贫血的治疗中,促红细胞生成素EPO治疗肿瘤相关性贫血的研究是目前最活跃的方法之一。然而EPO治疗的安全性问题一直是争论的焦点。     

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。     

青海地区胃癌相关性贫血的临床研究

目的：通过青海地区胃癌患者的贫血状况的分析,明确本地区贫血与胃癌分期及化疗效果的相关性。方法：收集2004年6月到2008年4月来院治疗的胃癌患者258例,检查血常规以了解贫血的状况,分析贫血发生率与肿瘤分期的关系。跟踪病例化疗情况,分析化疗后贫血发生率及其与预后间的关系。结果：样本中贫血发生率为43.8%。其中女性中为51.8%;男性中为41.6%,无显著性差异。在258例病人中具有完整TNM分期的195例,胃癌患者的贫血发生率根据肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄不同有显著性差异。肿瘤在胃贲门区、胃体部、胃窦区贫血发生率无显著性差异。258例胃癌患者接受三周期化疗后,贫血病人为161例。其中化疗后出现贫血的病人有46例,疾病控制率（DCR）为78.26%,客观缓解率（ORR）为21.74%。而化疗后无贫血的17例病人,疾病控制率（DCR）94.12%,客观缓解率（ORR）为52.94%。贫血组和非贫血组的DCR和ORR有显著性差异。在化疗过程中,15例病人接受了输血治疗,没有关于铁剂及促红细胞生成素（Erythropoietin,EPO）治疗的记录。结论：按NCI标准判断,青海地区胃癌相关性贫血的发生率与国内其他地区发生率相近。胃癌相关性贫血的发生率与肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄有关。化疗过程中发生贫血的病人对化疗的反应差,化疗过程中未发生贫血的病人疗效较好。本研究中贫血的发生率与患者性别及肿瘤的部位无关。     

青海地区胃癌相关性贫血的临床研究

目的:通过青海地区胃癌患者的贫血状况的分析,明确本地区贫血与胃癌分期及化疗效果的相关性。方法:收集2004年6月到2008年4月来院治疗的胃癌患者258例,检查血常规以了解贫血的状况,分析贫血发生率与肿瘤分期的关系。跟踪病例化疗情况,分析化疗后贫血发生率及其与预后间的关系。结果:样本中贫血发生率为43.8%。其中女性中为51.8%;男性中为41.6%,无显著性差异。在258例病人中具有完整TNM分期的195例,胃癌患者的贫血发生率根据肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄不同有显著性差异。肿瘤在胃贲门区、胃体部、胃窦区贫血发生率无显著性差异。258例胃癌患者接受三周期化疗后,贫血病人为161例。其中化疗后出现贫血的病人有46例,疾病控制率(DCR)为78.26%,客观缓解率(ORR)为21.74%。而化疗后无贫血的17例病人,疾病控制率(DCR)94.12%,客观缓解率(ORR)为52.94%。贫血组和非贫血组的DCR和ORR有显著性差异。在化疗过程中,15例病人接受了输血治疗,没有关于铁剂及促红细胞生成素(Erythropoietin,EPO)治疗的记录。结论:按NCI标准判断,青海地区胃癌相关性贫血的发生率与国内其他地区发生率相近。胃癌相关性贫血的发生率与肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄有关。化疗过程中发生贫血的病人对化疗的反应差,化疗过程中未发生贫血的病人疗效较好。本研究中贫血的发生率与患者性别及肿瘤的部位无关。     

IL-8及其受体在肿瘤进展与治疗中的研究进展

 白介素-8（IL-8）是趋化因子CXC亚家族成员之一，是机体先天免疫系统中参与免疫反应的重要介质。近年来研究证实，白介素-8在多种肿瘤组织及患者血清中含量显著升高，如乳腺癌、鼻咽癌、结直肠癌及胃癌等，与患者预后和TNM分期存在明显相关性。研究表明，白介素-8是肿瘤微环境中不可缺少的一种重要炎性反应因子和免疫抑制因子，不仅可以促进肿瘤进展，参与肿瘤血管生成，还具有招募免疫抑制细胞抑制抗肿瘤免疫应答的能力，更与肿瘤的耐药息息相关。本文综述了IL-8相关的肿瘤靶向治疗、与其他抗肿瘤方法联合应用的研究进展。     

重组人红细胞生成素治疗化疗相关性贫血的疗效观察

目的 评价重组人红细胞生成素(Recombinant Human Erythropoietin Injection,rHuEPO)治疗肿瘤化疗相关性贫血的疗效和安全性.方法 化疗相关性贫血的患者36例,其中21例行rHuEPO治疗,用法为:150 u/kg·次,皮下注射3次/周,疗程418周,同时给予中药及支持治疗.15例未用rHuEPO治疗.所有36例患者若出现严重贫血则给予输血治疗,以保证化疗继续进行.观察rHuEPO对血红蛋白(Hb)、红细胞比容(Hct)等的影响,以及对患者生活质量的影响和副反应.结果 治疗组治疗后Hb水平显著提高,4周有效率66.7%,对照组无明显提高;治疗组治疗后两周内网织红细胞计数显著提高,对照组治疗前后无变化.应用rHuEPO无严重副反应发生,安全性高,患者生活质量有所改善.结论 rHuEPO治疗肿瘤化疗相关性贫血的疗效肯定.rhuEPO不仅有效提高Hb水平,而且安全性高,副反应少,能够改善患者生存质量.     

Cancer-related anemia: pathogenesis, prevalence and treatment

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy--either alone or in combination with radiotherapy--had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients' quality of life and may also improve the clinical outcome.     

Cancer-related anemia

Anemia has a high prevalence in patients with cancer. Its frequency and severity depend on tumor type, tumor stage, duration of disease, and treatment status. The etiology of cancer-related anemia is multifactorial and includes myelotoxicity of treatment, bone marrow infiltration, impaired erythropoietin production, blood loss, and the anemia of chronic disease. Anemia affects health-related quality of life (QOL) and may impact on tolerance or even outcome of anticancer therapy. Despite its high prevalence and impact on QOL, anemia is often under-recognized and under-treated. Treatment should correct etiologic factors, whenever possible. Symptomatic treatments are red blood cell transfusions and administration of erythropoietic growth factors. Transfusions result in rapid improvement of anemia-related symptoms but are usually only given to patients with moderate to severe anemia. Administration of epoetins (epoetin alfa, epoetin beta) or darbepoetin alfa increases hemoglobin levels, reduces the need for blood transfusions, and improves QOL in patients with cancer-related anemia. Trials determining the exact association of anemia with both response to chemo(radio)therapy and survival are ongoing. Physicians should be aware of the clinical relevance of and treatment options for anemia in cancer patients.     

相关炎症因子在胃癌进展中的研究进展

胃癌的发生发展是多因素共同作用的结果,包括环境、生物和遗传因素等,促炎因子以及抗炎因子起着重要的作用。越来越多的研究报道了炎性因子与胃癌易感性存在着重要的联系。相关炎症因子以多种途径促进胃癌的进展,包括直接激活NF—κB刺激肿瘤细胞、上调黏附因子及促进肿瘤周围血管再生,以上途径还可抑制机体免疫,促使肿瘤细胞进展和转移。目前的研究已经发现了许多炎症因子在胃癌的发生发展中起到了重要作用。     

恶性肿瘤性贫血患者红细胞分布宽度分析

目的探讨恶性肿瘤性贫血患者的红细胞体积分布宽度(RDW)的差异。方法用SCC型血细胞分析仪检测恶性肿瘤性贫血组和正常健康组RDW值。结果轻度恶性肿瘤性贫血组和中重度恶性肿瘤性贫血组RDW值分别为15.43和15.36,均高于正常对照组,差异有统计学意义(P<0.001)。结论恶性肿瘤性贫血患者RDW值明显高于正常人。     

Anemia, hypoxia and transfusion in patients with cervix cancer: a review.

BACKGROUND AND PURPOSE: With the recent development of hemopoietic growth factors and alternatives to transfusion, there has been a renewed interest in the relationships between anemia, tumor hypoxia and treatment outcome in a number of human malignancies. This review is intended to provoke a reconsideration of these issues and their effect on clinical trials, aimed at improving treatment outcome in patients with cervix cancer. MATERIALS AND METHODS: Using data from the literature and from our own prospective series of tumor oxygenation in cervix cancer, we modeled the impact of anemia on tumor blood flow and hypoxia in animal models and human tumors, examined the relationship between anemia and hypoxia and treatment outcome in patients, and reviewed the impact of transfusion on tumor hypoxia and treatment outcome in cervix cancer. RESULTS: Anemia may result in a significant reduction in oxygen delivery to tumors, but compensatory mechanisms reduce the impact on tumor oxygenation. Anemia is associated with inferior treatment outcome in cervix cancer, but hemoglobin levels prior to and during treatment are strongly correlated with tumor size, and this may explain the prognostic impact of anemia in older studies. Transfusion and erythropoietin ameliorate hypoxia in only a proportion of anemic patients. Critical analysis of the published data from the Princess Margaret Hospital randomized trial of transfusion in cervix cancer reveals that, when analyzed by intention-to-treat, transfusion did not result in a benefit to patients. CONCLUSIONS: This review suggests that the relationships among anemia, hypoxia, transfusion and treatment outcome are complex. Further study of anemia as an independent prognostic factor is required and randomized studies of transfusion alternatives, such as erythropoietin, must be of sufficient size to detect small treatment effects.     

Anemia in malignant tumor diseases. V. The relation of tumor-induced hypotransferrinemia and the degree of anemia

Transferrin is a growth factor in malignancy. In this function, transferrin is taken up into the proliferating malignant cell. The tumor-induced loss of circulating transferrin results in a hypotransferrinemia which correlates with tumor mass and proliferation rate. The cellular uptake of iron into the erythropoietic precursors depends on the presence of iron-saturated transferrin. Thus, iron utilization for the hemoglobin synthesis correlates with the transferrin concentration in blood. In 256 patients with malignancies of different histological types and different tumor extension a strong correlation was found between the degree of tumor-induced hypotransferrinemia and anemia. This correlation between transferrin concentration and hemoglobin concentration could be demonstrated in the different histological tumor entities. Tumor progression was accompanied by a progressive fall in transferrin concentration and hemoglobin concentration. By contrast, tumor remission achieved by an effective antineoplastic therapy resulted in an improvement of hypotransferrinemia and anemia. These variations in the two parameters were found to be strongly correlated. We conclude from our data that tumor-induced loss of transferrin is one of the most important factors responsible for the development of anemia in malignancy.     

结直肠癌术前不同贫血类型与肿瘤特征、全身炎症和生存的关系

目的:探究术前不同贫血类型的结直肠癌患者与肿瘤的特征性参数和全身炎症反应之间的关系,以及术前不同贫血类型的结直肠癌患者的预后情况。方法:回顾性分析航天中心医院普外科2013年01月至2015年12月收治的118例结直肠癌手术患者的临床资料。根据患者的血红蛋白浓度（Hb）、平均红细胞体积（MCV）、平均血红蛋白含量（MCH）、平均血红蛋白浓度（MCHC）情况将患者分为无贫血组、正常细胞贫血组、小细胞性贫血组。比较分析三组患者的一般资料、肿瘤学特征资料和mGPS评分等。术后随访5年,观察生存情况,应用Kaplan-Meier法绘制生存曲线,采用Log-rank检验进行生存分析。应用Cox比例风险回归模型对结直肠癌患者进行影响预后的单因素和多因素分析。结果:本研究中结直肠癌患者术前贫血率为45.8%（54/118）。术前不同贫血类型患者中,在性别、体重减轻程度、CA724、肿瘤部位、肿瘤大小、TNM分期、mGPS评分、Ki-67阳性表达率等方面,差异均具有统计学意义（P＜0.05）。无贫血组5年生存率为59.4%,平均生存时间为49个月;小细胞性贫血组5年生存率为29.4%,平均生存时间为34个月;正常细胞性贫血组5年生存率为35.1%,平均生存时间为41个月。无贫血组与小细胞性贫血组和正常细胞性贫血组生存时间比较,差异均具有统计学意义（χ2=5.462,P=0.019; χ2=4.187,P=0.041）。单因素分析结果显示:肿瘤标记物CA199、肿瘤大小、TNM分期、有无远处转移、有无淋巴结转移、mGPS评分、Ki-67阳性表达率、贫血类型等方面是影响结直肠癌患者预后的相关因素（P＜0.05）。多因素分析结果显示:肿瘤大小、TNM分期、有无远处转移、mGPS评分、Ki-67阳性表达率、贫血类型等方面是影响结直肠癌患者预后的独立危险因素（P＜0.05）。结论:术前不同类型贫血的结直肠癌患者的肿瘤学特征不同,并且全身性炎症可能与术前贫血的状态有关。术前贫血与全身炎症状态是结直肠癌患者预后的独立危险因素。因此,在病人术前准备阶段,应尽可能恢复和改善贫血和全身炎症状态,以获得更好的结直肠癌预后,延长患者的生存时间。     

Anemia, tumor hypoxemia, and the cancer patient

PURPOSE: To review the impact of anemia/tumor hypoxemia on the quality of life and survival in cancer patients, and to assess the problems associated with the correction of this difficulty. METHODS: MEDLINE searches were performed to find relevant literature regarding anemia and/or tumor hypoxia in cancer patients. Articles were evaluated in order to assess the epidemiology, adverse patient effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer cell growth and/or therapeutic resistance. Past and current clinical studies of radiosensitization via tumor oxygenation/hypoxic cell sensitization were reviewed. All clinical studies using multi-variate analysis were analyzed to show whether or not anemia and/or tumor hypoxemia affected tumor control and patient survival. Articles dealing with the correction of anemia via transfusion and/or erythropoietin were reviewed in order to show the impact of the rectification on the quality of life and survival of cancer patients. RESULTS: Approximately 40-64% of patients presenting for cancer therapy are anemic. The rate of anemia rises with the use of chemotherapy, radiotherapy, and hormonal therapy for prostate cancer. Anemia is associated with reductions both in quality of life and survival. Tumor hypoxemia has been hypothesized to lead to tumor growth and resistance to therapy because it leads to angiogenesis, genetic mutations, resistance to apoptosis, and a resistance to free radicals from chemotherapy and radiotherapy. Nineteen clinical studies of anemia and eight clinical studies of tumor hypoxemia were found that used multi-variate analysis to determine the effect of these conditions on the local control and/or survival of cancer patients. Despite differing definitions of anemia and hypoxemia, all studies have shown a correlation between low hemoglobin levels and/or higher amounts of tumor hypoxia with poorer prognosis. Radiosensitization through improvements in tumor oxygenation/hypoxic cell sensitization has met with limited success via the use of hyperbaric oxygen, electron-affinic radiosensitizers, and mitomycin. Improvements in tumor oxygenation via the use of carbogen and nicotinamide, RSR13, and tirapazamine have shown promising clinical results and are all currently being tested in Phase III trials. The National Comprehensive Cancer Network (NCCN) guidelines recommend transfusion or erythropoietin for symptomatic patients with a hemoglobin of 10-11 g/dl and state that erythropoietin should strongly be considered if hemoglobin falls to less than 10 g/dl. These recommendations were based on studies that revealed an improvement in the quality of life of cancer patients, but not patient survival with anemia correction. Phase III studies evaluating the correction of anemia via erythropoietin have shown mixed results with some studies reporting a decrease in patient survival despite an improvement in hemoglobin levels. Diverse functions of erythropoietin are reviewed, including its potential to inhibit apoptosis via the JAK2/STAT5/BCL-X pathway. Correction of anemia by the use of blood transfusions has also shown a decrement in patient survival, possibly through inflammatory and/or immunosuppressive pathways. CONCLUSIONS: Anemia is a prevalent condition associated with cancer and its therapies. Proper Phase III trials are necessary to find the best way to correct anemia for specific patients. Future studies of erythropoietin must evaluate the possible anti-apoptotic effects by directly assessing the tumor for erythropoietin receptors or the presence of the JAK2/STAT5/BCL-X pathway. Due to the ability of transfusions to cause immunosuppression, most probably through inflammatory pathways, it may be best to study the effects of transfusion with the prolonged use of anti-inflammatory medications.     

Anemia in lung cancer: clinical impact and management

Anemia has a high prevalence in patients with lung cancer. Its frequency and severity depend on tumor stage, duration of disease, and previous and current treatment. Anemia affects the health-related quality of life and impacts prognosis and outcome of therapy. Despite this clinical relevance, anemia is often underrecognized and undertreated. Treatment options include the administration of hematopoietic growth factors and red blood cell transfusions. Blood transfusions result in rapid but often transient improvement of anemia. Administration of epoetin or darbepoetin alfa increases hemoglobin levels, decreases blood transfusions, and improves quality of life in patients with lung cancer. Trials determining the exact association of anemia with response to chemotherapy/radiation therapy and survival are ongoing. Oncologists must be aware of the clinical relevance of anemia and offer adequate treatment options to their patients.