Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis

6 patients with amyotrophic lateral sclerosis were treated with intravenous infusion of 100-200 million IU per day of human leukocyte interferon. Side effects of treatment included fever, chills, malaise, nausea, marked leukopenia, mild anemia, and thrombocytopenia. Tiredness, confusion, papilledema, and overall signs of acute encephalitis were observed. Tendon reflexes and muscle force decreased. EEG activity was slowed, and evoked potentials showed significant slowing of conduction times. Neuropsychological tests revealed congitive dysfunction. The syndrome of inappropriate antidiuretic hormone secretion developed in all patients. All side effects were reversible with cessation of interferon treatment.     

Monitoring FTD in the peripheral blood mononuclear cells of elderly patients with metastatic colorectal cancer administered FTD plus bevacizumab as first-line treatment

Trifluridine/tipiracil (FTD/TPI) is an orally administrated anticancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC) or gastric cancer. FTD, a key component of FTD/TPI, exerts antitumor effects via its incorporation into DNA. Using specific antibodies against bromodeoxyuridine, FTD incorporation into DNA is detected in tumors and peripheral blood mononuclear cells (PBMC) of patients with mCRC who are administered FTD/TPI. The proportion of FTD-positive PBMC fluctuates according to the schedule of treatment, although the association between the proportion of FTD-positive PBMC and the clinical outcomes of patients is unknown. To answer this question, here we monitored the FTD-positive PBMC of 39 elderly patients with mCRC enrolled in KSCC1602, a single-arm phase 2 trial of FTD/TPI plus bevacizumab as a first-line treatment, for 1 month, during the first cycle of treatment. The median values and interquartile ranges of the percentage of FTD-positive PBMC on days 8, 15, and 29 were 39.3% (30.7%-52.2%), 66.9% (40.0%-75.3%), and 13.5% (5.7%-26.0%), respectively. Receiver operating characteristic analysis revealed that the percentage of FTD-positive PBMC on day 8 (the end of the first week of treatment) had moderate ability to accurately diagnose the occurrence of severe neutropenia and leukopenia within 1 month (area under the curve = 0.778 [95% confidence interval, 0.554-0.993]). This result suggests that excess FTD incorporation into PBMC at the initial phase of FTD/TPI plus bevacizumab treatment is a risk factor for early onset of severe hematological adverse events.     

利奈唑胺相关性血液毒性的危险因素分析

目的 探讨接受利奈唑胺治疗住院患者发生相关性血液毒性的危险因素。方法 采用单中心、观察性、回顾性研究。收集78例接受利奈唑胺治疗且监测血药浓度的住院患者的临床资料,多因素Logistic回归分析其相关危险因素。结果 Logistic回归分析显示利奈唑胺疗程[OR=1.296（1.094~1.53）,P=0.003],肾小球滤过率估计值<30 mL·min^-1·（1.73 m²）^-1[OR=11.582（1.870~71.729）,P=0.008]是白细胞减少症的显著危险因素;利奈唑胺首次谷浓度[OR=1.178（1.052~1.318）,P=0.005],基础血白蛋白值< 30 g·L^-1[OR=4.175（1.315~13.254）,P=0.015]是血小板减少症的显著危险因素。结论 利奈唑胺相关性白细胞减少症呈时间依赖,相关性血小板减少症呈浓度依赖,患者在治疗期间应密切监测血常规,情况许可下建议监测血药浓度,行个体化治疗。     

扶正升白颗粒对辐射后小鼠白细胞减少症的实验研究

目的研究扶正升白颗粒对辐射后小鼠外周血白细胞减少症的影响。方法将50只小鼠随机分为5组:正常对照组、模型对照组、鲨肝醇+利血生组、扶正升白颗粒常规剂量组、扶正升白颗粒1/2剂量组。经~(60)Co γ射线照射制备小鼠白细胞减少症模型,造模成功后各组分别给予相应药物灌胃,分别于给药前(第1 d、第5 d、第10 d)观测小鼠外周血象白细胞计数。结果扶正升白颗粒常规剂量组升白细胞作用更明显(P0.05)。结论扶正升白颗粒可明显促进射线照射所致白细胞减少症模型,小鼠白细胞数量的恢复,表明扶正升白颗粒有升白作用。     

甲巯咪唑治疗甲状腺功能亢进症致白细胞减少症60例临床观察

目的探讨甲巯咪唑治疗甲状腺功能亢进症致白细胞减少的原因及治疗。方法回顾性总结应用甲巯咪唑治疗甲状腺功能亢进症导致白细胞减少症患者60例的临床资料。结果 60例患者发生白细胞减少时间均在服药治疗第1~6周内,患者(60/60)均发生在服甲巯咪唑15~30 mg/d治疗阶段。60例患者中有6例因粒细胞缺乏改用131I治疗;25例经升高白细胞治疗1周白细胞计数、中性粒细胞计数达标;28例治疗2周逐渐恢复正常;1例治疗4周恢复正常。总有效率为98.3%。结论药物毒性及遗传易感性可能是甲巯咪唑致白细胞减少的主要原因,一旦发生,应予以及时处理。     

Liquid formulation of pentoxifylline is a poorly tolerated treatment for duchenne dystrophy

Introduction: In this study we performed an open‐label, pilot study of an orally administered liquid formulation of immediate‐release pentoxifylline (PTX) on patients with Duchenne muscular dystrophy (DMD). Treatment efficacy, safety, and tolerability were assessed. Methods: The tolerability and safety of PTX and measures of muscle strength and function were evaluated during 12 months of treatment. Results: Seventeen boys with DMD, between 4 and 8 years of age, were enrolled at one of five Cooperative International Neuromuscular Research Group (CINRG) centers. Only 9 were able to complete the 12‐month PTX treatment phase; the primary reason for discontinuation was adverse events. Intolerable gastrointestinal side effects were experienced by 65% of participants. Two participants had severe leukopenia that resolved with medication withdrawal. Conclusions: Open‐label treatment with a liquid formulation of immediate‐release PTX resulted in a high incidence of adverse events in boys with DMD. Poor tolerability of this PTX formulation precluded adequate assessment of efficacy. Muscle Nerve, 2011     

减量化疗肝动脉栓塞治疗肝癌合并白细胞和（或）血小板减少的研究

目的研究减量化疗肝动脉栓塞对伴有白细胞和（或）血小板减少的原发性肝癌治疗的安全性及有效性。方法回顾性分析292例行减量化疗肝动脉栓塞治疗的原发性肝癌病例。所有病例伴有白细胞≤3.0×10^9/L和（或）血小板≤50×10^9/L。全组292例分成3组,A组伴有白细胞减少85例;B组伴有血小板减少41例;C组同时伴有白细胞和血小板减少166例。结果全组中位生存期23.0月,1年生存率72.2%;A、B和C组中位生存期分别为26.0月、36.0月和20.0月,1年生存率分别为73.6%、87.5%和69.5%。对292例患者作单因素及多因素生存分析显示,白细胞≤2.0×10^9/L（r=0.657,P=0.016）、肿瘤〉5 cm（r=3.175,P=0.000）和白蛋白≤35 g/L（r=0.452,P=0.000）是生存时间的独立影响因素,血小板计数不是生存的影响因素。60例（20.5%）患者在介入治疗术前和（或）术后使用重组人粒细胞集落刺激因子（granulocyte colony stimulating factor,G-CSF）,用药与否对生存没有影响。介入术后1月内随访白细胞与血小板均无明显下降,所有患者无严重骨髓抑制发生。结论减量化疗肝动脉栓塞治疗伴有白细胞和（或）血小板减少的原发性肝癌是安全有效的。     

地榆升白片预防及治疗恶性肿瘤放疗后白细胞减少的系统分析

目的:系统评价地榆升白片治疗和预防恶性肿瘤放疗后白细胞减少的有效性。方法:计算机检索Cochrane图书馆、PubMed、CBM、VIP、CNKI、万方数据库,起止时间均从建库至2011年03月。手工检索其他血液病相关杂志。对纳入的地榆升白片治疗和预防恶性肿瘤放疗后白细胞减少的随机对照试验进行质量评价,并进行Meta分析。结果:共纳入研究6篇。META分析显示白细胞降低分度例数上,地榆升白片优于对照组,差异有统计学意义[RR=1.54,95%CI(1.31,1.81)P=0.24,RR=1.21,95%CI(0.65,2.23)P=0.50],但与重组粒细胞集落刺激因子相比无显著性差异[RR=1.21,95%CI(0.65,2.23)P<0.05]。结论:地榆升白片能有效治疗和预防恶性肿瘤放疗后白细胞减少症。由于纳入研究少、研究质量普遍不高,上述结果有待高质量大样本的随机双盲对照试验加以验证。     

黄芪联合参麦注射液在白细胞减少症中的疗效观察

目的探讨黄芪联合参麦注射液在白细胞减少症中的疗效。方法将245例白细胞减少症患者随机分为治疗组125例,对照组120例,两组在年龄、性别、疾病程度上比较差异无统计学意义,具有可比性。对照组采用口服鲨肝醇20mg,3次/d;利血生20mg,3次/d;维生素B420mg,3次/d,饭后服药。治疗组:采用黄芪注射液20ml,参麦注射液60ml加入5%葡萄糖注射液250ml中静脉滴注,1次/d,连用20d。结果治疗组总有效率98.4%,对照组总有效率80.83%,两组总有效率比较P<0.05差异有统计学意义。结论采取黄芪联合参麦注射液治疗白细胞减少症临床疗效确切,无明显的毒副作用,安全可靠,是治疗白细胞减少症首选药物。     

丝裂霉素和5-氟尿嘧啶诱发小鼠血小板减少、白细胞减少动物模型的建立

目的建立化疗药物丝裂霉素、5-氟尿嘧啶诱发小鼠血小板减少、白细胞减少的动物模型。方法采用不同用法用量的丝裂霉素、5-氟尿嘧啶给予小鼠,在不同时间进行血液学检查,确定丝裂霉素、5-氟尿嘧啶能够引起小鼠血小板减少、白细胞减少的合适剂量和成模时间。结果腹腔注射丝裂霉素首剂量为25或50mg.kg-1、维持量为12.5mg.kg-1,5-氟尿嘧啶腹腔注射首剂量为125或187.5mg.kg-1、维持量为62.5mg.kg-1,外周血WBC和PLT均显著降低,与空白组比较,差异有统计学意义(P<0.01)。丝裂霉素首剂量50mg.kg-1、维持量12.5mg.kg-1,5-氟尿嘧啶首剂量187.5mg.kg-1、维持量62.5mg.kg-1,其RBC均降低,与空白组比较,差异有统计学意义(P<0.01)。结论采用上述剂量的丝裂霉素、5-氟尿嘧啶可诱发复制小鼠白细胞减少、血小板减少模型,成功率较高,动物死亡率低。