三氧化二砷联合全反式维A酸、柔红霉素治疗小儿急性早幼粒细胞白血病的临床疗效

目的　评价全反式维A 酸、柔红霉素与三氧化二砷联合方案治疗小儿急性早幼粒细胞白血病（APL）的临床疗效。方法　选取2010 年10 月～2013 年10 月在我院血液科接受治疗的34 例急性APL 患儿作为研究对象。采用数字随机法分为对照组和实验组，每组17 例。对照组患儿使用维A 酸、柔红霉素治疗，实验组在维A 酸、柔红霉素基础上联合三氧化二砷静脉注射治疗。对两组患儿的临床治疗效果和长期生存情况进行观察比较。结果　经过28 天的治疗，试验组患儿完全缓解率显著高于对照组（94.11% vs. 82.35%，P<0.05）；两组达到完全缓解时间、白细胞峰值、早期死亡率和感染率等指标的差异均有统计学意义（P<0.05）；试验组的PML-RARα 转阴率较对照组高，但差异无统计学意义（P>0.05）。对患儿跟踪随访36 个月，对照组与试验组患儿的总生存时间分别为21.22±3.78）月、（32.08±4.56）月、无复发生存时间分别为（11.71±4.21）月、（20.27±3.93）月，随访期内死亡率分别为5.88%、17.64%，试验组生存情况均优于对照组，差异有统计学意义（P<0.05）。结论　三氧化二砷联合全反式维A 酸、柔红霉素治疗方案能够提高APL 患儿的完全缓解率并改善长期生存情况，条件许可时，可以作为首选方案。     

急性早幼粒细胞白血病的治疗

急性早幼粒细胞性白血病(APL)常用化疗药物主要包括柔红霉素和(或)依达比星(idarubicin),此外还包括其他蒽环类抗生素和阿糖胞苷等,全反式维A酸(ATRA)为第一个分子靶向治疗药物,与三氧化二砷、造血干细胞移植(SCT)等也是重要的治疗方案。     

三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病29例

目的观察三氧化二砷（As2O3）联合全反式维甲酸（ATRA）治疗急性早幼粒细胞白血病（APL）的疗效及毒副反应。方法患者使用三氧化二砷联合全反式维甲酸双诱导治疗,对高白细胞患者加用单一化疗药物高三尖衫酯碱（H）或柔红霉素（DNR）,合并弥漫性血管内凝血（DIC）患者予以输注血浆／纤维蛋白原。结果29例患者中26例完全缓解,完全缓解（CR）率89．66％;3例死于颅内出血。结论三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病的疗效确切,患者耐受性较好。     

高三尖杉酯碱与柔红霉素在急性早幼粒细胞白血病中的研究

目的对高三尖杉酯碱与柔红霉素治疗急性早幼粒细胞白血病的效果进行对照研究。方法回顾性分析我院2013年1月1日至2019年9月31日收治的44例初治急性早幼粒细胞白血病患者,其中对照组26例患者采用柔红霉素联合维甲酸及亚砷酸治疗,观察组18例患者采用高三尖杉酯碱联合维甲酸及亚砷酸治疗,对比两组患者的治疗效果。结果观察组和对照组的有效率分别为100%,对照组为94.44%,组间比较无明显差异(P>0.05)。观察组的KPS改善率为88.89%,明显高于对照组的69.23%(P <0.05)。结论对急性早幼粒细胞白血病采用高三尖杉酯碱与柔红霉素治疗效果无明显差异,但是在生存质量方面,采用高三尖杉酯碱治疗效果更为理想。     

柔红霉素联合阿糖胞苷对急性早幼粒细胞白血病的疗效分析

目的:研究在维甲酸、亚砷酸联合诱导基础上,不同时间应用柔红霉素联合阿糖胞苷对低危组急性早幼粒细胞白血病(APL)的疗效。方法:初治急性早幼粒细胞白血病低危组患者23例,根据白细胞(WBC)计数变化调整化疗方案的合理应用时间,观察在白细胞上升至10×109/L(观察组)及20×109/L(对照组)时加用柔红霉素联合阿糖胞苷的作用效果,以达到提高完全缓解(CR)率,减少APL分化综合征(DS)、弥散性血管内凝血(DIC)等严重并发症的治疗目标。结果:两组初诊WBC计数比较,差异无统计学意义(P>0.05),但治疗后观察组中WBC平均上升速率及上升最高值均低于对照组,且观察组中的DS发生率低于对照组;观察组中位CR时间为26.3 d,对照组中位CR时间为39.6 d,观察组明显早于对照组;另一方面,两组DIC的发生率和CR率比较,差异均无统计学意义(P>0.05)。结论:根据白细胞计数变化(≥10×109/L)加用化疗,可提高低危组急性早幼粒细胞白血病诱导化疗的治疗效果,有效控制疾病进展。     

全反式维甲酸、亚砷酸和柔红霉素方案治疗初诊急性早幼粒细胞白血病观察

目的探讨全反式维甲酸、亚砷酸和柔红霉素方案治疗初诊急性早幼粒细胞白血病的临床效果。方法选择桂林市医学院附属医院2005年1月至2010年1月急性早幼粒细胞白血病触诊患者32例,将上述患者分为两组,观察组和对照组。观察组患者给予亚砷酸10mg加入生理盐水500mL中静脉滴注,每天1次,连续用药到患者为完全缓解;给予全反式维甲酸每天30~60mg口服;给予柔红霉素每天20~40mg,在第1~3天和第15~17天静脉注射。对照组患者给予全反式维甲酸每天30~60mg口服。结果观察组治疗1周后早幼粒细胞和白细胞总数分别与对照组比较,差异有统计学意义(P<0.05);两组完全缓解率比较,差异有统计学意义(P<0.05)。结论全反式维甲酸、亚砷酸和柔红霉素方案能够显著提高初诊急性早幼粒细胞白血病完全缓解率,临床效果显著。     

亚砷酸在急性早幼粒细胞白血病治疗中的效果分析

目的分析亚砷酸在急性早幼粒细胞白血病[1]治疗中的效果。方法选取我院2012年3月至2014年11月收治的急性早幼粒细胞白血病患者36例,进行随机分组,分为治疗组与对照组两组,对照组采用维甲酸联合化疗[2]的方法对患者进行治疗,治疗组在对照组的基础上增加亚砷酸联合化疗,进行维甲酸和亚砷酸双诱导联合化疗[3]的方法对患者进行治疗。针对两组的各临床指标如有无发生不良反应、症状缓解时间等进行分析研究。结果经过数据比较,可见治疗组的疗效优于对照组,更有利于急性早幼粒细胞白血病患者的治疗。结论急性早幼粒细胞白血病可采取维甲酸和亚砷酸双诱导联合化疗方法,亚砷酸可以改善急性早幼粒细胞白血病的临床治疗效果。     

维甲酸和亚砷酸双诱导联合化疗对初诊急性早幼粒细胞白血病的治疗效果

目的观察维甲酸和亚砷酸双诱导联合化疗对急性早幼粒细胞白血病的临床治疗效果。方法将收录的52例急性早幼粒细胞白血病患者随机的分为4组,A组13例患者采取维甲酸和亚砷酸双诱导联合化疗;B组13例患者采取维甲酸联合化疗;C组13例患者采取亚砷酸联合化疗;D组13例患者采取化疗,观察4组的治疗效果。结果通过4组的治疗效果分析,A组患者的症状完全缓解率明显的高于B、C、D三组的情况,并且病死率也明显的低于C、D组的情况,比较具有明显的差异(P<0.05),统计学有意义;A组患者的高白细胞血症的持续时间与症状缓解时间均明显的低于B、C、D组的情况,比较具有明显的差异(P<0.05),统计学有意义。结论对初诊急性早幼粒细胞白血病患者采取维甲酸和亚砷酸双诱导联合化疗治疗效果明显,而且治疗更准确,可靠性强,值得临床中应用。     

全反式维甲酸联合三氧化二砷治疗初发急性早幼粒细胞白血病的近期疗效分析

目的分析全反式维甲酸与三氧化二砷联合治疗初发急性早幼粒细胞白血病的近期疗效。方法随机将我院2012年10月至2015年10月收治的90例初发急性早幼粒细胞白血病患者分为两组各45例,对照组患者给予全反式维甲酸治疗,观察组患者联合全反式维甲酸和三氧化二砷进行治疗,比较两组患者的近期疗效。结果观察组CR率为88.9%,对照组CR率为71.1%,比较具有统计学差异(P<0.05);观察组和对照组患者达CR时间、白细胞峰值及PML/RARα转阴率的对比具有统计学差异(P<0.05)。结论联合三氧化二砷与全反式维甲酸治疗急性早幼粒细胞白血病的近期疗效明显,值得临床推广和运用。     

急性髓系白血病应用去甲氧柔红霉素及柔红霉素的诱导治疗研究

目的比较去甲氧柔红霉素及柔红霉素诱导治疗急性髓系白血病的临床疗效。方法回顾性分析急性髓系白血病患者42例的临床资料,其中19例患者采用柔红霉素+阿糖胞苷治疗为柔红霉素组,23例患者采用去甲氧柔红霉素+阿糖胞苷治疗,为去甲氧柔红霉素组。比较两组的完全缓解率、有效率和不良反应。结果去甲氧柔红霉素组CR 78.3%,总有效率为91.3%,显著高于柔红霉素组的42.1%和47.4%(P<0.05或0.01)。结论去甲柔红霉素联合阿糖胞苷诱导治疗急性髓系白血病,与柔红霉素联合阿糖胞苷方案比较,能够显著提高完全缓解率及总有效率。     

全反式维甲酸与亚砷酸联合化疗对急性早幼粒细胞白血病高危患者的疗效

目的观察全反式维甲酸(ATRA)与亚砷酸(ATO)联合化疗对急性早幼粒细胞白血病(APL)患者的疗效。方法回顾性分析86例不同危险分级的初治APL患者的临床资料。根据治疗前白细胞和血小板数将APL患者分为低、中、高危三组。采用ATRA+ATO+蒽环类药诱导缓解,蒽环类药+阿糖胞苷巩固治疗,ATRA+ATO+甲氨蝶呤(MTX)[部分加用6-巯基嘌呤(6-MP)]维持治疗。结果治疗后,完全缓解(CR)率高达95.3%(82/86)。中位随访37个月,高危组和中低危组无事件生存率及中枢神经系统累积复发率差异均无统计学意义(P>0.05)。维持治疗单用MTX者或MTX+6-MP者CR率均为100%。结论 APL患者尤其是高危患者可以从ATO+ATRA+化疗中受益;该方案作为初治APL的一线治疗方案优势明显。     

Pathogenesis and treatment of leukemia: an Asian perspective

INTRODUCTION: Leukemias occur worldwide, but there are important geographic differences in incidences. AREAS COVERED: Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. EXPERT OPINION: In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.     

Arsenic trioxide: new preparation. Acute promyelocytic leukaemia: encouraging results but persistent doubts

(1) Acute promyelocytic leukaemia is a rare disease. There is a high remission rate after combination treatment with tretinoin and anthracycline, but there is no established treatment for refractory or relapsed disease. Further treatment with tretinoin, combined with intensive cytotoxic chemotherapy, seems to give the best results in patients who qualify for this treatment, but assessment is limited. (2) Arsenic trioxide has now been approved for induction of remission and consolidation in patients with refractory or relapsed acute promyelocytic leukaemia. (3) The clinical evaluation dossier that supported the application contains data from two non comparative trials including 12 and 40 patients. A complete haematological response was obtained in 45 (87%) of the 52 patients, and the survival rate among patients in first relapse was 77% after a median follow-up of two years. These results are similar to those previously obtained with tretinoin plus intensive cytotoxic chemotherapy. (4) All the patients treated with arsenic trioxide experienced adverse events. This was to be expected given the acute and chronic toxicity of arsenicals. Most events included fatigue, gastrointestinal disturbances, peripheral neuropathies, prolongation of the QT interval; and biochemical disturbances (hypokalaemia, hyperglycaemia, elevated transaminase activity). (5) Like tretinoin, arsenic trioxide can provoke a potentially severe leukocyte activation syndrome. (6) In practice, these encouraging data justify further assessment of arsenic trioxide. This drug is already an option for patients with refractory or relapsed disease who cannot receive tretinoin plus intensive chemotherapy.     

Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic leukemia (APL) patient: speciation of arsenic metabolites in serum and urine

The pharmacokinetics of arsenic species in a Japanese patient with relapsed acute promyelocytic leukemia (APL) treated with arsenic trioxide at a daily dose of 0.08 mg/kg was investigated. After achieving complete remission on Day 35 during the induction therapy of arsenic trioxide, we collected the serum and urine samples on Days 4 and 5 during the consolidation therapy of arsenic trioxide. The concentrations of inorganic arsenic and the methylated metabolites in serum and urine were measured by HPLC/ICP-MS. The patient restricted taking the seafood for 3 d before the start of administration and during the sampling period in order to avoid the influence of arsenic derived from seafood. Arsenite (As(III)), methylarsonic acid (MMAs(V)), and dimethylarsinic acid (DMAs(V)) were detected in serum and urine. The total concentration of As(III), MMAs(V) and DMAs(V) in serum ranged from 18 to 41 microg/l (240-547 nM) during 24 h on Day 4. The amount of total arsenic (As(III)+MMAs(V)+DMAs(V)) in urine was 4464 microg/d on Day 4. These results suggest that not the micro-molar but the nano-molar order of arsenic in serum is sufficient to produce the therapeutic effect on APL cells.     

Eugenol,a plant-derived phenolic nutraceutical,protects thiol (SH) group in myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by arsenic trioxide – a in vivo model study

Arsenic trioxide is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is narrow due to different organ toxicities. It is hypothesized that the generation of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative damage in rat myocardium. In this study, the defensive effect of eugenol on thiol-based oxidative stress was investigated in arsenic trioxide-treated rats. Rats were orally administered with arsenic trioxide (4?mg/kg per day) alone and in combination with eugenol (5?mg/kg per day) for 30?days. Reduction in relative organ weight, total thiol level, protein thiol content, acid-soluble thiol content, thioredoxin activity, and protein content was witnessed in arsenic trioxide-treated rats. Additionally, the total antioxidant activity, tissue GSH level, and GSH/GSSG ratio were considerably diminished. However, the co-treatment of eugenol noticeably sheltered the arsenic trioxide-mediated cardiotoxicity. In conclusion, eugenol is a prospective phenolic compound, of natural origin, for protecting the thiol group in myocardium from oxidative stress by chemotherapeutic compounds.     

Leukemia, an effective model for chemical biology and target therapy

The rapid rise of chemical biology aimed at studying signaling networks for basic cellular activities using specific, active small molecules as probes has greatly accelerated research on pathological mechanisms and target therapy of diseases. This research is especially important for malignant tumors such as leukemia, a heterogeneous group of hematopoietic malignancies that occurs worldwide. With the use of a chemical approach combined with genetic manipulation, great progress has been achieved over the past few decades on the biological, molecular and cytogenetic aspects of leukemia, and in its diagnosis and therapy. In particular, discoveries of the clinical effectiveness of all-trans retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia and the kinase inhibitors Imatinib and Dasatinib in the treatment of chronic myelogenous leukemia not only make target therapy of leukemia a reality, but also push mechanisms of leukemogenesis and leukemic cell activities forward. This review will outline advances in chemical biology that help our understanding of the molecular mechanisms of cell differentiation and apoptosis induction and target therapy of leukemia.     

难治及复发性恶性血液病采用三氧化二砷联合化疗对预后影响

目的：观察三氧化二砷联合化疗方案治疗难治及复发性恶性血液病的效果。方法：随机从我院2009年6月一2014年6月收治的难治及复发性恶性血液病患者中抽取60例作为研究对象，根据治疗方案将其分为对照组和观察组，每组各30例。其中对照组使用单纯化疗方案治疗，观察组则使用三氧化二砷联合化疗的方案治疗，对比两组的临床效果和毒性反应。结果：经对比，观察组患者的总有效率为86．67％，显著高于对照组的66．67％，差异具有统计学意义（P〈0．05）。同时，观察组的毒性反应发生率为30％，显著低于对照组的66．67％，差异具有统计学意义（P〈0．05）。结论：对难治及复发性恶性血液病采用三氧化二砷联合化疗治疗具有显著疗效，降低不良反应，有助于改善患者的预后。     

全反式维甲酸和三氧化二砷治疗初治急性早幼粒细胞白血病的疗效观察

目的观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗初治急性早幼粒细胞白血病(APL)的疗效。方法对应用ATRA和As2O3联合诱导治疗的20例APL患者的完全缓解(CR)率、达CR所需时间和不良反应进行观察,并与单独应用ATRA组30例进行比较。联合用药组治疗方法为ATRA 25mg/(m2.d),0.1%As2O310ml/d直至CR。结果联合用药组与单独应用ATRA组相比,CR率差异无统计学意义(分别为95%、86.7%,均P>0.05);联合用药组获得CR所需的时间短于单独用药组(平均时间分别为24d、45d,均P<0.05),早期死亡率较单独用药组差异无统计学意义(分别为5%、13.3%,均P>0.05);与单独用药组相比,联合用药组的不良反应并未增加。结论联合用药诱导初发APL缓解的疗效优于单用药组,不良反应少,是一种值得推广应用的方案。