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。     

急性早幼粒细胞白血病18例临床分析

目的　探讨急性早幼粒细胞白血病(APL)的临床特点、最佳治疗方案、维A酸综合征(RAS)的防治。方法　分析18例APL患者的临床资料。结果　18例APL患者中以出血起病16例。维A酸联合化疗治疗8例,疗程>6周期2例,分别于第2 6个月、第72个月复发死亡;2例早期死亡;4例<4周期者2例无病生存5年以上,2例于5年后复发,治疗后再次完全缓解。维A酸、砷剂联合化疗治疗10例无病生存2～37个月。结论　APL是一种特殊类型急性白血病,临床以出血为主要症状,RAS以预防为主。     

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。     

三氧化二砷治疗急性早幼粒细胞白血病疗效观察

目的 :观察三氧化二砷 (As2 O3)治疗急性早幼粒细胞白血病的完全缓解率、高白细胞发生率、肝功损害及融合基因转阴率 ,并与维甲酸 (ATRA )的治疗情况进行比较。方法 :随机分为两组 ,As2 O3组 17例 ,ATRA组 2 1例 ,分别选用 0 .1% As2 O310 m L/ d,静脉滴注 ;ATRA2 5 mg· m- 2 · d- 1 ,分 3次服用。分别观察两组的完全缓解率 (CR)、不良反应以及融合基因转阴率。结果 :As2 O3组 15 / 17例 (88.2 % )获 CR,获得 CR时间为 (2 8.1± 4 .6 ) d;ATRA组 19/2 1例 (90 .4 % )获 CR,获得 CR时间为 (39.4± 8.6 ) d,两组之间 CR无明显差别 ,但 As2 O3组获得 CR时间明显缩短。高白细胞发生率 As2 O3组 10 / 15例 (6 6 .7% ) ,ATRA组 18/ 19例 (94 .7% ) ,P<0 .0 5。肝功能异常 ,As2 O3组 11/ 17例(6 4 .7% ) ,ATRA组 13/ 19例 (6 8.4 % ) ,P>0 .0 5。所有患者治疗前 PML- RARα融合基因阳性。 As2 O3组 CR时 ,2 /14例 (14 % )转阴 ,ATRA组 2 / 19例 (10 .5 % )转阴 ,P<0 .0 5。CR后 1a,As2 O3组 5 / 8例 (6 2 .5 % )转阴 ,ATRA组 4 /11例 (36 .3% )转阴 ,P<0 .0 5。As2 O3组 15例获 CR者 ,无 1例复发。ATRA组 19例获 CR者 ,4例 (2 1% )复发。结论 :与 ATRA相比 As2 O3获得 CR时间缩短 ,高白细胞发生率低 ,CR及 CR     

Tamibarotene

Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials. Clinical trials held in Japan showed that tamibarotene had efficacy in APL patients who had relapsed from ATRA-induced complete remission. Recently, better understanding of the various mechanisms of action of retinoids has stimulated great interest in its potential use for treatment of various diseases. Tamibarotene is being investigated for treatment of multiple myeloma and Crohn's disease in clinical trials. This review focuses on tamibarotene's mechanisms of action, chemical properties, pharmacokinetics and its use in APL as well as its potential use in various disorders.     

急性早幼粒细胞白血病46例临床分析

目的：总结46例急性早幼粒细胞白血病（APL）的治疗、预后及不良反应,以达到提高缓解率,延长生存期的目的。方法：对46例APL患者治疗期间应用全反式维甲酸、亚砷酸、DA/MA/HA及复方黄黛片进行联合治疗。结果：本组46例APL患者除2例早期死亡外,其余44例均达到完全缓解（CR）,CR率为95.7%。结论：应用全反式维甲酸、亚砷酸及复方黄黛片联合治疗APL是安全有效的,对初治或复发患者均具有疗效高、耐受性好的特点。     

急性早幼粒细胞白血病21例临床分析

目的 探讨急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)合并出血的临床特点和防治方法.方法 回顾性分析21例APL患者的临床特点及疗效.结果 初诊时合并出血症状20例(95.2%),合并弥漫性血管内凝血(DIC)10例(47.6%),早期死亡5例(23.8%),经全反式维A酸等治疗及血小板及凝血因子输注后完全缓解13例(61.9%).结论 APL出血发生率高,全反式维A酸(ATRA)的应用、血小板及凝血因子输注等治疗可以减少早期出血病死率.     

细胞遗传学在急性早幼粒细胞白血病的诊断及预后评估中的作用

目的探讨细胞遗传学在急性早幼粒细胞白血病（APL）的诊断及预后评估中的应用价值。方法应用常规细胞遗传学分析APL初诊患者39例,采用R显带技术进行染色体核型分析。随访分析完全缓解率、复发率。结果39例APL患者中,染色体异常38例,其中30例为典型t（15;17）易位,8例为涉及15和17号染色体的复杂核型。形态学误诊为M2和M5各1例,经核型分析确诊。经全反式维甲酸和（或）化疗联合诱导治疗,37例获完全缓解,2例具有复杂核型者未取得完全缓解,6例具有复杂核型者第1次完全缓解后3年内复发,复发率86％（6／7）,其他核型组完全缓解后3年内复发率仅10％（3／31）。结论细胞遗传学对细胞形态不典型APL具有确诊价值,复杂染色体异常者预后不佳。     

三氧化二砷联合全反式维甲酸治疗初发急性早幼粒细胞白血病临床分析

目的三氧化二砷联合全反式维甲酸治疗初发急性早幼粒细胞白血病的临床疗效(即完全缓解率和融合基因PML-RARα转阴情况)及不良反应。方法 46例初发APL患者随机分成研究组予As2O3联合ATRA治疗24例,对照组仅予ATRA治疗22例,均治疗直至CR。根据外周血白细胞计数、维甲酸综合征以及肝功能变化调整两药物的剂量。观察CR率、获得CR和不良反应。结果 46例初发APL患者,ATRA联合As2O3组24例患者中,CR23例,1例未缓解,缓解率95.8%,ATRA单药组22例患者中,CR17例,5例未缓解,缓解率77.3%。两组间CR率差异有统计学意义。65.0%患者在治疗开始后出现白细胞升高,63.8%出现肝功能异常,多在减量或停用后1周内恢复。所有患者融合基因PML-RARα初发时均为阳性,CR时9.8%转阴。结论 As2O3联合ATRA治疗初发APL疗效好,不良反应少。长期完全缓解时间需要进一步观察。     

Targeted therapies for the myeloid leukaemias

Although the standard approach to myeloid leukaemias remains chemotherapy, the agents currently available rarely result in cure. Recent advances in understanding the biology of these disorders have lead to the development of targeted treatment strategies. In acute promyelocytic leukaemia (APL), all-trans retinoic acid (ATRA), sodium phenylbutyrate and arsenic trioxide are agents which either induce differentiation or apoptosis and have been used to successfully achieve remission. The tyrosine kinase inhibitor, STI-571, antisense oligonucleotides, and bcr-abl vaccines are strategies which focus on the oncogenic events in chronic myelogenous leukaemia (CML). Two anti-CD33 monoclonal antibody conjugates, Y90-HuM195 and CMA-676, have been used in acute myelogenous leukaemia (AML) and have shown some efficacy. Although the preliminary results with these targeted therapies are promising, further studies are needed to establish them as effective, less toxic alternatives to the current standard of care.     

Targeted therapies for the myeloid leukaemias

Although the standard approach to myeloid leukaemias remains chemotherapy, the agents currently available rarely result in cure. Recent advances in understanding the biology of these disorders have lead to the development of targeted treatment strategies. In acute promyelocytic leukaemia (APL), all-trans retinoic acid (ATRA), sodium phenylbutyrate and arsenic trioxide are agents which either induce differentiation or apoptosis and have been used to successfully achieve remission. The tyrosine kinase inhibitor, STI-571, antisense oligonucleotides, and bcr-abl vaccines are strategies which focus on the oncogenic events in chronic myelogenous leukaemia (CML). Two anti-CD33 monoclonal antibody conjugates, Y90-HuM195 and CMA-676, have been used in acute myelogenous leukaemia (AML) and have shown some efficacy. Although the preliminary results with these targeted therapies are promising, further studies are needed to establish them as effective, less toxic alternatives to the current standard of care.     

粒系集落刺激因子与急性早幼粒细胞白血病关系的研究

24例急性早幼粒细胞白血病（APL）患者，在全反式维甲酸（ATRA）治疗过程中，用ELISA法检测其血清、骨髓单个核细胞及NB4细胞用ATRA诱导前后上清液及冻融物中G－CSF水平。结果表明，在治疗前血清中G－CSF检出率为20．8％，治疗后检出率升高，在白细胞达高峰前阳性率最高，而后逐渐下降。上清液及冻融物中G－CSF均未能检出。分析表明血清G－CSF水平与外周血白细胞呈正相关（P＜0．05）。结果提示G－CSF在APL患者用ATRA治疗过程中白细胞升高的发生机制中起一定作用，APL细胞不分泌G－CSF。     

亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床分析

目的探讨亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床效果。方法将本院2008年1月～2013年9月收治的64例急性早幼粒细胞白血病患者随机分为4组,每组各16例。联合组给予亚砷酸和全反式维甲酸进行双诱导治疗,亚砷酸组给予亚砷酸治疗,维甲酸组给予全反式维甲酸治疗,化疗组给予常规化疗治疗。结果联合组、亚砷酸组的所有患者（100％）完全缓解,无死亡病例,维甲酸组13例（81．2％）患者达到完全缓解,1例死亡,化疗组仅6例（37．5％）完全缓解,2例死亡,前3组的完全缓解率均显著高于化疗组（P〈0.05）;联合组患者用药至完全缓解的时间明显短于亚砷酸组、维甲酸组（P〈0.05）;联合组患者凝血指标恢复正常所用的时间短于亚砷酸组、维甲酸组（P〈0.05）;肝功能损伤情况：联合组最严重,亚砷酸组次之,维甲酸组较轻,化疗组最轻（P〈0.05）,化疗组的胃肠道反应、皮肤损伤情况较严重,受影响患者明显多于其他3组（P〈0.05）。结论亚砷酸联合维甲酸治疗急性早幼粒细胞白血病短期效果显著,完全缓解率高,并可缩短患者的完全缓解时间。     

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.     

亚砷酸持续输注联合小剂量维A酸治疗急性早幼粒细胞性白血病临床观察

目的 探讨亚砷酸（ATO）持续输注联合小剂量维A酸（LD—ATRA）治疗急性早幼粒细胞白血病（APL）的有效性及安全性。方法6例初治APL采用ATO持续输注联合LD—ATRA方法治疗,ATO按10mg·d^-1加入5％葡萄糖500ml稀释,持续输注18h;ATRA按15mg·d^-1,连续口服1周：观察疗效、外周WBC、出凝血指标及不良反应？结果6例均达到CR,获CR时间为（25．3±1．03）d,无早期死亡与CNS—L发生。所有病例在治疗1周后,出凝血指标均恢复正常。外周血WBC均有增多,仅1例WBC超过30×10^9／L。不良反应轻,主要为Ⅰ～Ⅱ度肝功能损害,Ⅰ度恶心呕吐。结论ATO持续输注联合LD—ATRA方法治疗APL,具有疗效好,不良反应轻等优点,值得进一步研究.     

Arsenic trioxide for management of acute promyelocytic leukemia: current evidence on its role in front-line therapy and recurrent disease

INTRODUCTION: Acute promyelocytic leukemia (APL), the most rapidly fatal leukemia only two decades ago, has been converted into the most frequently curable leukemia by the advent of all-trans retinoic acid (ATRA) and its combination with anthracycline-based chemotherapy. More recently, arsenic trioxide (ATO) has been shown to be the most effective single agent in this disease and has been approved for the treatment of relapsed patients both in the United States and Europe. Moreover, ATO has been included in the design of several front-line studies, with the aim to reduce therapy-related toxicity while maintaining the potential of cure. AREAS COVERED: First, this review briefly discusses the mechanisms of action and the toxicity profile of ATO. Furthermore, the reported experience on the use of ATO as single agent or in combinatorial schemes both in relapsed and in newly diagnosed patients with APL is critically reviewed. Finally, the use of this agent in special subsets of patients unfit to receive conventional chemotherapy is discussed, along with its potential role in maintenance therapy. EXPERT OPINION: While the role of ATO as single agent or in combination with ATRA is well established and recommended by the European LeukemiaNet guidelines as a first option for relapsed patients, the role of the drug in newly diagnosed patients is still uncertain and based only on evidence levels mostly originating from non-randomized trials. The results of ongoing randomized studies should better define the role of ATO in front-line therapy.