重组人粒细胞集落刺激因子治疗老年软组织肉瘤患者化疗后骨髓抑制的临床观察

目的观察比较两种方法应用重组人粒细胞集落刺激因子(rhG-CSF)治疗老年软组织肉瘤患者化疗引起白细胞下降的效果,为临床用药提供指导。方法选择解放军总医院骨科2010年1月至2014年1月经由我院病理科确诊的原发性软组织肉瘤老年患者82例,全部采用MAID(美司钠、多柔比星、异环磷酰胺及达卡巴嗪)化疗方案,随机分为两组,A组患者在全部化疗给药结束后24 h内应用rhG-CSF注射液2.5μg/kg,1次/d,连续应用14 d至白细胞≥4.0×10~9/L停药。B组患者于全部化疗给药结束后监测血常规,当达到Ⅱ级骨髓抑制时应用rhG-CSF注射液5μg/kg,1次/d,连续应用7 d或白细胞≥4.0×10~9/L停药。观察患者化疗后白细胞最低值、恢复到的最高值及恢复时间、用药时间及次数。结果 (1)两组患者在一般情况方面差异无统计学意义(P0.05)。(2)两组患者的白细胞最低值差异无统计学意义(P0.05),B组患者的白细胞最高值及恢复时间略低于A组(P0.05)。(3)B组患者在用药时间及用药次数方面明显低于A组患者(P0.05)。结论 B组患者采用的高剂量短时间给药方法可确切提高外周血白细胞数目,同时减轻患者所受痛苦,值得临床应用。     

重组人血小板生成素的临床应用观察

目的:评价沈阳三生制药厂的重组人血小板生成素(rhTPO)对患者血小板减少的疗效和安全性。方法:11例血液恶性肿瘤患者和9 例难治性ITP患者皮下注射rhTPO1.0g/(kg·d),动态监测注射后血小板增长情况。结果:肿瘤化疗组使用rhTPO 9 d后,血小板计数较对照组明显升高(P<0.05),血小板恢复至100×109/L需19±9.4 d,较对照组24±6.2天明显缩短。难治性ITP组显效6例,良效3例,总有效率100%。无明显不良反应。结论:rhTPO对化疗后骨髓抑制引起的血小板减少及难治性ITP患者的严重血小板减少有促进血小板生成作用,无明显不良反应。     

应用重组人血小板生成素减少肝硬化患者术前血小板输注疗效初步研究*

目的 以输注血小板改善肝硬化并发血小板减少症患者出血风险的疗效不确切,且可能导致潜在的并发症。本研究的目的是探讨应用重组人血小板生成素注射液(rhTPO)能否减少肝硬化患者术前输注血小板。方法 2017年1月～2019年4月在西京医院消化内科住院并进行手术治疗的乙型肝炎肝硬化患者40例和肝细胞癌患者36例,均需行食管静脉曲张套扎和/或胃底静脉曲张组织胶注射术或经肝动脉化疗栓塞术(TACE)治疗。术前给予rhTPO 15000U皮下注射,1次/d,连续应用10 d。结果 在76例患者中,血小板计数为40～50×10⁹/L组23例,血小板计数<40×10⁹/L组53例;两组患者在治疗第8 d时,外周血血小板计数较基线明显升高【>50×10⁹/L,分别为(76.0±26.6)×10⁹/L和(54.4±24.3)×10⁹/L]。在治疗第12 d,两组外周血血小板计数达到高峰[分别为(95±34.8)×10⁹/L和(67.9±25.1)×10⁹/L],在治疗后第30 d,血小板计数降至基线水平;应用rhTPO治疗后,保证了手术的顺利进行,对血凝功能无明显影响,两组未观察到门静脉血栓形成。结论 rhTPO可作为肝硬化并发血小板减少症患者术前血小板输注的替代疗法,能降低术中出血风险,且安全,值得临床进一步验证。     

重组人血小板生成素在急性髓系白血病诱导缓解期后的临床运用

目的 :研究国产全长人血小板生成素 (rhTPO)对急性髓系白血病 (AML)患者化疗后血小板减少的疗效和安全性。方法 :采用非随机自身对照。 2 8例AML诱导缓解后的患者在试验周期化疗后 ,皮下注射rhTPO1.0 μg/kg ,每日 1次 ,疗程 14d。对照周期不用rhTPO。动态观察全血细胞计数 ,定期复查肝肾功能、凝血酶原时间 (PT)、活化的部分凝血活酶时间 (aPTT)和纤维蛋白原、心电图。结果 :试验周期化疗后血小板最低值为(16 .93± 2 0 .2 7)× 10 9/L ,血小板 <2 0× 10 9/L的持续天数为 (4 .75± 5 .97)d ,输血小板的次数和量分别为 (1.5 4± 1.79)次和 (2 1.6 1± 2 9.73)u ,与对照周期相比差异均无统计学意义 (P >0 .0 5 )。化疗后血小板最高值及血小板计数恢复的增加值 (差值 )试验周期分别为 (2 5 5 .89± 2 13.0 7)× 10 9/L和 (2 38.96± 2 10 .4 3)× 10 9/L ,明显高于对照周期的 (15 0 .2 2± 10 7.6 4 )× 10 9/L和 (135 .0 7± 10 5 .75 )× 10 9/L(P <0 .0 5 )。用rhTPO对其他监测指标无明显影响。不良反应也少而轻微。结论 :国产全长rhTPO治疗AML耐受性良好 ,确实能提高AML化疗后的血小板计数 ,但对总体血小板恢复时间及血小板输注的需要没有明显影响。     

重组人促血小板生成素改善脓毒症患者心肌损伤的临床研究

目的探讨脓毒症患者使用重组人促血小板生成素治疗后心肌损伤标志物、心功能、炎症因子水平等变化规律,以判断其对临床预后的作用。 方法选择上海市第一人民医院急诊危重症医学科病房2016年1月至2019年4月收治的符合Sepsis3.0诊断标准的脓毒症患者186例,根据是否使用重组人促血小板生成素(rhTPO)将其分为对照组和rhTPO组。收集基本信息资料、临床数据资料、炎症因子和免疫功能指标预后生存状态等,主要监测指标为患者心肌损伤标志物TnI和心功能BNP,次要监测指标为炎症因子IL-6和TNF-α。 结果使用rhTPO患者第七天心肌损伤指标血清心肌坏死标记物：心肌肌钙蛋白I(TnI)较未使用rhTPO患者下降幅度大(0.6471±0.4145 vs. 0.2517±0.1347μg/L,P＝0.006) ;使用rhTPO患者第七天心功能指标脑钠肽BNP较未使用rhTPO患者下降幅度大(529.4±251.1 vs. 306.1±53.52 pg/ml,P<0.0001)。rhTPO可以降低反映内皮损伤的炎症因子IL-6、TNF-α。使用rhTPO患者第七天炎症指标IL-6较未使用rhTPO患者下降幅度明显增大(843.3±514.0 vs. 357.1±84.71 pg/ml,P<0.0001)。使用rhTPO患者第七天炎症指标TNF-α较未使用rhTPO患者下降幅度明显增大(9.771±9.051 vs. 5.850±1.621 pg/ml, P<0.0001)。 结论rhTPO可以改善脓毒症心肌损伤、心功能,改善脓毒症炎症指标。     

重组人促红细胞生成素治疗慢性病贫血45例疗效观察

目的探讨重组人促红细胞生成素（rHuEPO）治疗慢性病贫血（ACD）的疗效和安全性。方法选取88例在我院门诊及住院部治疗的ACD病例,随机分为观察组（45例）和对照组（43例）,观察组患者皮下注射rHuEPO,2次／周,3000U／次,连用8周;观察组和对照组对原发病的治疗方案一致,两组间伴缺铁ACD患者均静脉滴注蔗糖铁,3次／周,100mg／次。共用8周。疗程结束后比较两组患者治疗前后血液学指标Hb、MCV、MCH、MCHC及血清铁（SI）、总铁结合力（sF）、转铁蛋白饱和度（sTfR）的变化情况,并记录药物不良反应。结果观察组40例患者疲乏无力、心悸气短、头昏眼花、食欲不振等贫血症状在治疗后有不同程度改善。Hb由（75．2±11．6）g／L增至（100．5±9．8）g／L（P〈0．01）;MCV、MCHC、SI、SF、sTfR有所改善（P〈0．01 orP〈0．05）;对照组患者贫血症状无明显改善,其中6例在治疗过程中因贫血加重需输血,上述的各项指标治疗前后比较差异无统计学意义。结论rHuEPO治疗ACD可在一定程度上改善贫血,减轻患者贫血症状,减少输血,使用安全。rHuEPO用于ACD患者的治疗具有一定的实用价值。     

重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床试验

目的 评价国产重组人血小板生成素(rhTPO)对慢性难治性特发性血小板减少性紫癜(ITP)的疗效和安全性。方法 慢性难治性ITP患者皮下注射rhTPO 1.0μg/kg,1次/d,疗程14 d。结果 82例患者用药前血小板计数中位数为15.5(6.0-24.0)×109/L,给药起(5、7、15)d时分别升至27.5(16.0～47.0)×109/L、35.0(20.5-78.0)×109/L和77.0(41.8-119.5)×109/L,与用药前相比(P值均<0.01)。停药后血小板计数逐渐回落,至给药起第28天,血小板计数中位数降至76.5(35～120.3)×109/L,但仍明显高于治疗前(P<0.01)。近期有效率85.3％,其中显效58.5％(血小板≥100×109/L,无出血症状),良效26.8％(血小板升至50×109/L或较原水平上升30×109/L以上,无或基本无出血症状)。仅3例出现轻微临床不良反应。16例中1例在给药起21 d和28 d的血清中检测出低滴度抗TPO抗体,但不具有中和活性。结论 rhTPO可一过性升高慢性难治性ITP患者的血小板计数,不良反应轻微。     

重组血小板生成素联合地塞米松治疗原发免疫性血小板减少症的疗效

目的探讨重组血小板生成素(rh TPO)联合地塞米松治疗原发免疫性血小板减少症(ITP)的临床效果。方法选择2012年2月至2014年3月在该院接受治疗的60例ITP患者。以数字法随机分成观察组和对照组各30例,观察组予地塞米松联合rh TPO治疗,对照组单纯使用地塞米松治疗,1个疗程(28 d)后比较两组临床疗效、血小板水平变化及不良反应情况。结果观察组的总有效率〔93.33%(28/30)〕显著优于对照组〔73.33%(22/30)〕(χ2=7.283,P=0.007)。两组在治疗前、治疗1~7 d的血小板水平差异均无统计学意义(t=0.432,0.588;P=0.682,0.312);治疗后7~14 d、14~28 d观察组血小板水平均显著高于对照组(t=13.981,12.925;均P=0.000)。观察组不良反应率为23.33%(7/30),对照组为16.67%(5/30),两组比较差异无统计学意义(χ2=2.857,P=0.091)。结论 rh TPO联合地塞米松治疗ITP疗效显著,不良反应少,值得推广。     

Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia

We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey's serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO-treated animals exhibited no significant changes in several serum parameters, C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.     

白血病化疗相关药物所致血小板减少症治疗的研究进展

白血病化疗药物如环磷酰胺、吉西他滨、柔红霉素等可引起不同程度的血小板减少,进而导致皮肤黏膜及重要脏器出血而使化疗终止,甚至危及生命。目前临床上主要是通过输注血小板、应用促血小板生成药物等展开对症治疗。该文对白血病化疗后血小板减少症的发病机制、输血治疗、rh TP0和rh IL-11等促血小板生长因子治疗等方面进行了综述。     

Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies

We investigated the effects of recombinant human thrombopoietin (rhTPO) on the growth of megakaryocytic (MK) colony derived MK progenitors from human cord blood (CB) in vitro and the effects of gestational age on the number of MK colonies. The results demonstrated that rhTPO alone supports the growth of MK colonies and induces not only proliferation but also differentiation of MK progenitors. CB shows a high frequency of MK colonies; most of which are very large and equivalent to high proliferative potential colony-forming unit-megakaryocyte. The colonies could be macroscopically observed as white spots in the culture dish. Preterm neonates showed greater numbers of MK progenitors than term neonates and there was an inverse correlation between gestational age and concentration of MK progenitors of CB. The effects of gestational age was an important factor on the proliferative capacity of MK progenitors and on the response to rhTPO.     

Autoantibodies to thrombopoietin and the thrombopoietin receptor in patients with immune thrombocytopenia

Autoantibodies to thrombopoietin (TPO, also termed THPO) or the TPO receptor (cMpl, also termed MPL) could play a pathological role in immune thrombocytopenia (ITP). In this study, we tested for autoantibodies against TPO, cMpl, or the TPO/cMpl complex in ITP and other thrombocytopenic disorders. Using an inhibition step with excess TPO in fluid‐phase to improve binding specificity, the prevalence of anti‐TPO autoantibodies was: active ITP: 9/32 (28%); remission ITP: 0/14 (0%); non‐immune thrombocytopenias: 1/10 (10%); and healthy controls: 1/11 (9%). Similarly, using an inhibition step with excess cMpl, the prevalence of specific anti‐cMpl autoantibodies was: active ITP: 7/32 (22%); remission ITP: 1/14 (7%); non‐immune thrombocytopenias: 3/10 (30%); and healthy controls: 0/11 (0%). Two active ITP patients had autoantibodies against the TPO/cMpl complex, but not against TPO or cMpl alone. Anti‐TPO or anti‐cMpl autoantibodies were found in 44% of ITP patients, and in 40% of patients with other thrombocytopenic disorders. These autoantibodies did not correlate with ITP disease severity or number of ITP treatments received; however, in this cohort, 3 patients failed to respond to TPO receptor agonist medications, and of those, 2 had anti‐TPO autoantibodies. This suggests that anti‐TPO and anti‐cMpl autoantibodies are associated with thrombocytopenia, and may be clinically relevant in a subset of ITP patients.     

A novel recombinant human thrombopoietin for treating prolonged isolated thrombocytopenia after allogeneic stem cell transplantation

Patients with prolonged isolated thrombocytopenia (PT) after allogeneic stem cell transplantation (allo-SCT) are known to have a poor prognosis. However, there is no standard treatment for PT. The present study aimed to investigate the potential effect of a novel recombinant human thrombopoietin (rhTPO) in a cohort of patients with PT following allo-SCT. A total of 24 patients with PT (including delayed platelet engraftment and secondary failure of platelet recovery) were treated with rhTPO from July 1, 2016 to May 31, 2017. rhTPO injections were administered at 300 IU/kg/d for 28 consecutive days or until platelet counts were ≥ 50 × 10⁹/L, independent of platelet transfusion. Response was defined as platelet recovery to ≥ 20 × 10⁹/L for seven consecutive days without transfusion support during or within 7 days of the end of rhTPO treatment. All patients completed the 28 days of treatment, and none were withdrawn due to adverse effects. The overall response was 45.8%, which was significantly higher than historical data (12.2%, p < 0.001). The median response time was 12 (7–25) days from the initiation of rhTPO treatment. A response to rhTPO was associated with megakaryocytes in the bone marrow (positive vs. negative, 81.8 vs. 22.2%; p = 0.022). Among 11 patients exhibiting a response to rhTPO, the median number of megakaryocytes in bone marrow was increased significantly (10 vs. 2; p = 0.036) after rhTPO treatment. In conclusion, the results of this preliminary study suggest that rhTPO may represent a therapeutic option, with a response of 45.8% for patients with PT after allo-SCT, and especially for those with megakaryocytes in the bone marrow. However, this should be further confirmed in randomized prospective clinical trials.     

原发性肺滑膜肉瘤诊断与治疗附1例报告及文献复习

目的 通过探讨原发性肺滑膜肉瘤的临床症状、影像学表现、病理学及免疫组化,提高对本病的认识.方法 报告近期呼吸科确诊1例原发性肺滑膜肉瘤患者,同时对既往报道18例患者进行回顾性研究,分析其临床表现、影像学表现、病理学特征及免疫组化特点.结果 临床表现为咳嗽、咳痰或胸痛、胸闷等,影像学表现为肺部肿块影,边缘清楚或呈分叶状,病灶密度不均匀,增强扫描呈不均匀强化,可伴纵隔淋巴结肿大及胸腔积液,病理学检查提示为梭形细胞恶性肿瘤,瘤细胞呈流水状排列,核分裂象易见,免疫组化EMA、Bcl-2、Vimentin等阳性.结论 原发性肺滑膜肉瘤临床表现及影像学表现上无特异性,不易与其他肺或胸膜原发性肉瘤相鉴别,需要结合病理及免疫组化结果进行诊断.