急性早幼粒细胞白血病维甲酸和砷剂治疗期间组织因子改变的 …

探讨急性早幼粒细胞白血病发病初期和维甲酸及三氧化二砷治疗期间组织因子的表达。方法；采用ＥＬＩＳＡ法测定血浆可溶性纤维蛋白单体复合物，Ｄ－二聚体和细胞裂解液ＴＦ含量；ＲＴ－ＰＣＲ法测定细胞ＴＦ ｍＲＮＡ的转录情况。结果：发病时，患者血浆ＳＦＭＣ和Ｄ－Ｄ水平，骨髓分离的单个核细胞悬液的促凝活性，细胞裂解液的促凝活性，细胞裂解液的ＴＦ水平，ＴＦｍＲＮＡ的转录均显著升高，经ＡＴＲＡ和ＡＳ２Ｏ３治疗后显著降     

砷剂和维甲酸对 NB4细胞组织因子和凝血酶调节蛋白mRNA及促凝活性的影响

为了研究三氧化二砷(As203)和全反式维甲酸(ATRA)对NB4细胞组织因子(TF)和凝血酶调节蛋白(TM)mRNA及其表达的影响,本研究采用体外细胞培养方法,以As2O3、ATRA处理NB4细胞,用ELISA动态测定其TF、TM抗原表达及促凝活性(PCA)变化,用逆转录-聚合酶链反应(RT-PCR)测定TF和TM的mRNA转录.结果表明1 μmol/L的As2O3和1 μmol/L ATRA均可使NB4细胞TF抗原及mRNA表达呈时间依赖性渐进性下调;在24、48、72、96和120小时时间点,As2O3组TF抗原的表达水平分别为13.3±1.8,8.6±1.9,10.8±1.5,2.0±0.6和2.6±0.9 ng/107;ATRA组TF抗原的表达水平分别为12.4±1.1,11.3±1.8,5.7±1.7,2.8±0.8和2.0±0.6 ng/107,与对照组比较具有显著性(P＜0.05);在不同的时间点As2O3和ATRA,均可使其PCA下降,As2O3组血凝时间分别为123.5±10.5,156.3±11.6,179.3±15.3,248.9±20.1,312.0±29.8(秒);ATRA组血凝时间分别为76.4±5.6,146.8±10.9,198.2±15.6,265.8±20.6和363.8±31.9(秒);ATRA使NB4细胞TM抗原表达及其mRNA转录上调.结论As2O3、ATRA可降低TF mRNA转录,下调TF蛋白表达,降低NB4细胞PCA;ATRA增高TM转录及表达,缓解APL患者凝血功能异常.     

Retinoic acid syndrome: a review

The retinoic acid syndrome (RAS) is an unpredictable but frequent complication which may develop after administration of all- trans retinoic acid (ATRA) most commonly in patients with acute promyelocytic leukaemia (APL). In this review, we describe the incidence, predictive factors, clinical course, outcome and treatment of RAS in patients with APL treated with ATRA. The incidence of RAS in patients receiving ATRA is about 14–16%, with an associated mortality of about 2%. Initial high white blood cell (WBC) count, rapidly increasing WBC count and/or the presence of the CD 13 expression on leukaemic cells may help in identifying patients likely to develop RAS. Concurrent chemotherapy will probably decrease the risk of developing RAS but often exacerbates bleeding, leading to leucocytosis, thrombocytopenia, disseminated intravascular coagulation and fibrinolysis. Prophylactic steroids are not recommended but prompt administration of steroids at the first sign of unexplained dyspnea, fever, weight gain or pulmonary infiltrate, is critical. Liposomal ATRA is being investigated to induce haematological cure in APL without chemotherapy and to reduce the incidence of RAS but further validation of its usefulness is necessary.     

急性早幼粒细胞白血病全反式维甲酸治疗时IL—8及其受体表达 …

目的：探讨白细胞介素８（ＩＬ－８）及其Ａ型受体（ＩＬ－８ＲＡ）的表达在全反式维甲酸（ＡＴＲＡ）诱导治疗急性早幼粒细胞白血病（ＡＰＬ）中的临床意义。方法：动态检测ＡＰＬ患者１８例ＡＴＲＡ治疗中血浆ＩＬ－８水平（ＥＬＩＳＡ法）取３例骨髓单个核细胞（ＭＮＣ）加ＡＴＲＡ（１０＾－６ｍｍｏｌ／Ｌ）体外诱导，流式细胞仪动态检测ＭＮＣ膜Ｌ－８ＲＡ的表达。结果：ＭＮＣ加入ＡＴＲＡ诱导７２小时，上清ＩＬ－８水平明显     

全反式维甲酸、四硫化四砷、化疗三联方案在急性早幼粒细胞白血病维持治疗中的应用

目的比较全反式维甲酸（ATRA）、四硫化四砷（As4S4）、化疗三联方案与ATRA、化疗二联方案在急性早幼粒细胞白血病（APL）维持治疗中的疗效差异。方法60例APL患者经ATRA诱导分化达完全缓解（CR）后，用联合化疗巩固治疗。随后随机分为两组，三联组30例用ATRA＋As4S4＋化疗维持治疗，二联组30例仅应用ATRA＋化疗维持治疗。分析两种治疗方案的疗效、不良反应及对PML-RARα融合基因转阴的影响。结果三联组3年累计持续完全缓解（CCR）率为90．0％，二联组为63．3％，三联组PML—RARα融合基因转阴率明显高于二联组（分别为90％和63％，P〈0．05）。加用As4S4治疗不良反应未明显加重。结论APLCR患者巩固治疗后应用ATRA＋As4S4加化疗维持治疗，CCR率高，不良反应轻。     

Phosphatidylserine exposure and procoagulant activity in acute promyelocytic leukemia

Summary. Background: Acute promyelocytic leukemia (APL) frequently causes disseminated intravascular coagulation that can worsen with cytotoxic chemotherapy but improve with the therapeutic differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (As₂O₃). APL cells display tissue factor but the relationship of tissue factor and other procoagulant activity to phosphatidylserine (PS) exposure is largely unknown. Methods: Lactadherin, a milk protein with stereospecific binding to phosphatidyl‐L‐serine, was used as a probe for PS exposure on an immortalized APL cell line (NB4) and on the cells of eight patients with APL. PS exposure was evaluated with flow cytometry, confocal microscopy, coagulation assays, and purified prothrombinase and factor (F) Xase assays. Results: Plasma procoagulant activity of NB4 and APL cells increased approximately 15‐fold after exposure to etoposide or daunorubicin and decreased 80% after treatment with ATRA or As₂O₃. Procoagulant activity corresponded to exposed PS on viable APL cells. PS exposure decreased after treatment with ATRA or As₂O₃ and increased after treatment with daunorubicin or etoposide. Excess lactadherin inhibited 80–85% of intrinsic FXase, FVIIa‐tissue factor and prothrombinase activities on both NB4 cells and APL cells. Confocal microscopy identified membrane patches that stained with lactadherin, but not annexin V, demonstrating focal, low‐level PS exposure. Conclusions: PS is exposed on viable APL cells and is necessary for approximately 80% of procoagulant activity.     

维甲酸、砷剂及柔红霉素对NB4细胞组织因子表达的影响

目的　探讨全反式维甲酸（ Ａ Ｔ Ｒ Ａ） 、三氧化二砷（ Ａｓ２ Ｏ３） 及柔红霉素（ Ｄ Ｎ Ｒ） 对急性早幼粒细胞白血病（ Ａ Ｐ Ｌ） 细胞株 Ｎ Ｂ４ 细胞组织因子（ Ｔ Ｆ） 表达的影响。方法　用复钙时间检测 Ｎ Ｂ４ 细胞的促凝活性（ Ｐ Ｃ Ａ） ;用 Ｅ Ｌ Ｉ Ｓ Ａ 方法检测其 Ｔ Ｆ 抗原;用逆转录聚合酶链反应（ Ｒ Ｔ Ｐ Ｃ Ｒ） 检测 Ｔ Ｆｍ Ｒ Ｎ Ａ的转录水平。结果　 Ａ Ｔ Ｒ Ａ 和 Ａｓ２ Ｏ３ 均呈时间依赖的方式下调 Ｎ Ｂ４ 细胞的 Ｐ Ｃ Ａ、 Ｔ Ｆ 抗原水平以及 Ｔ Ｆ ｍ Ｒ Ｎ Ａ的转录;而 Ｄ Ｎ Ｒ 处理 Ｎ Ｂ４ 细胞的 Ｐ Ｃ Ａ及 Ｔ Ｆ 抗原在早期上调,至２４ ～４８ 小时达到最大值。对 Ｐ Ｃ Ｒ 产物测序,发现 Ａ Ｐ Ｌ 细胞 Ｔ Ｆ 第５ 个外显子缺失的转录本。结论　 Ａ Ｔ Ｒ Ａ 和 Ａｓ２ Ｏ３ 均可下调 Ａ Ｐ Ｌ 细胞 Ｔ Ｆ的表达并降低其 Ｐ Ｃ Ａ,改善 Ａ Ｐ Ｌ患者的弥散性血管内凝血（ Ｄ Ｉ Ｃ） 出血症状; Ａｓ２ Ｏ３ 和 Ｄ Ｎ Ｒ 对 Ａ Ｐ Ｌ凝血障碍不同效应的作用机制至少部分与药物对 Ａ Ｐ Ｌ细胞 Ｔ Ｆ 表达和 Ｐ Ｃ Ａ 的不同调节作用有关。     

不同急性早幼粒细胞白血病诊断性检验项目的周转时间及总消耗时间的比较

目的比较急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)诊断性检验项目的周转时间(turn around time,TAT)及总消耗时间(the elapsed time,TET),为APL的早期诊治提供指导。方法分别比较20例初诊APL患者确诊过程中的外周血形态及骨髓MICM(Morphology、Immunology、Cytogenetics、Molecular,MICM)分型检查的TAT,及每项实验和首次全反式维甲酸(all-trans retinoic acid,ATRA)治疗的TET(从入院开始计时)。结果 APL诊断性检验项目的 TAT/TET分别为:外周血形态外周血形态(2.6±2.6)h/(5.8±5.5)h,骨髓形态(初步)(2.4±0.5)h/(20.6±12.3)h,骨髓形态(正式)(26.9±19.9)h/(40.4±24.9)h,免疫分型(23.5±9.1)h/(62.1±32.2)h,染色体(259.9±82.8)h/(283.1±94.4)h、PML/RARa基因为(67.4±26.4)h/(98.5±39.6)h。分别与外周血形态的TAT及TET比较,除骨髓形态(初步)的TAT无统计学差异(P=0.246)外,其他项目的 TAT及TET均有显著性统计学差异(P0.01)。同时ATRA首次治疗的TET为(7.0±29.1)h,与外周血形态TET相比无统计学差异(P=0.778)。结论外周血形态能较快地为APL诊断提供方向,并有利于为骨髓形态的初步报告缩短TAT,两者联合能有效地为APL的及早ATRA救治提供实验依据,从而为降低早期死亡率(early death rate,EDR)创造条件。     

CNS relapses of acute promyelocytic leukemia after all-trans retinoic acid

OBJECTIVE: To review the role of all-trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL). CASE SUMMARY: A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia-retinoic acid receptoralpha (PML-RARalpha) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RARalpha fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood. DISCUSSION: APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85-95% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30-40%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966-January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS. CONCLUSIONS: The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.     

Clinical roundtable monograph. Early death in patients with acute promyelocytic leukemia

With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide, acute promyelocytic leukemia (APL) has become a highly curable malignancy. Approximately 90% of patients achieve complete remission with induction, which generally includes ATRA and an anthracycline-based chemotherapy. Early death, either before treatment is initiated or during induction, has emerged as one of the most critical issues involved in the current care of patients with APL. The main cause of early death in APL is bleeding, often intracranial. It has become increasingly clear that induction therapy should be initiated in patients at the earliest time possible, even before confirmation of the diagnosis of APL has been made. In this roundtable, several experts discuss important insights into the high rate of early death observed in APL. In addition to the importance of rapid diagnosis, the pathophysiology of the coagulopathy associated with APL will be discussed, as will factors that may be predictive of early death and potential interventions to prevent this important limitation to the cure of many, if not most, patients.     

Role of interleukin-8 and growth-regulated oncogene-alpha in the chemotactic migration of all-trans retinoic acid-treated promyelocytic leukemic cells toward alveolar epithelial cells

OBJECTIVE: Although all-trans retinoic acid (ATRA) can treat acute promyelocytic leukemia (APL), it also causes retinoic acid syndrome with presentations similar to acute respiratory distress syndrome. We investigated the role of interleukin (IL)-8 and growth-regulated oncogene (GRO)-alpha in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells. DESIGN: An in vitro human cell culture study. SETTING: University hospital research laboratories. SUBJECTS: NB4 and A549 cells. INTERVENTIONS: NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone for 1-3 days. NB4 or ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium located in a lower plate. MEASUREMENTS AND MAIN RESULTS: ATRA stimulated NB4 cells to transmigrate toward the A549 cells in a time- and dose-dependent manner. Replacement of A459 condition medium by its original medium abrogated this transmigration. Only A549 cells constitutively secreted GRO-alpha, and both A549 and NB4 cells constitutively secreted IL-8, which was enhanced by ATRA. Exogenous administration of IL-8 or GRO-alpha also promoted the ATRA-NB4 transmigration. The binding assay demonstrated that ATRA-NB4 cells bound IL-8, but not GRO-alpha, more avidly. Pretreatment with antibodies directed against IL-8 and GRO-alpha receptors reduced ATRA-NB4 transmigration by about 60%. Dexamethasone did not suppress their IL-8 secretion and transmigration in ATRA-NB4 cells, but when applied to A549 cells, IL-8 secretion was suppressed but not GRO-alpha secretion, and there was attenuation of ATRA-NB4 transmigration. CONCLUSIONS: IL-8 and GRO-alpha secreted from alveolar epithelial cells play an important role in the cell-cell interaction involved in the chemotactic transmigration of ATRA-treated APL cells toward alveolar epithelial cells.     

急性早幼粒细胞白血病基因分析

目的：分析急性早幼粒细胞白血病（ＡＰＬ）患者经全反式维甲酸（ＡＴＲＡ）联合细胞毒药物及异基因骨髓移植（ａｌｏ－ＢＭＴ）治疗后融合基因的变化。方法：采用逆转录－多聚酶链反应（ＲＴ－ＰＣＲ）对２２例ＡＰＬ患者治疗前后ＲＡＲα／ＰＭＬ融合基因进行检测。其中１２例患者为单纯化疗，１０例接受了ａｌｏ－ＢＭＴ，９例患者于第１次完全缓解（ＣＲ１）期、１例于第１次复发（ＲＲ１）期接受了ａｌｏ－ＢＭＴ。结果：单纯维甲酸诱导完全缓解时，７５％ＡＰＬ患者融合基因仍然阳性；继用强化疗后８３％患者融合基因转为阴性，ＲＴ－ＰＣＲ转阴时间为发病后１～３９个月；ａｌｏ－ＢＭＴ后４个月内及４个月后，分别有６２．５％及８５．７％患者融合基因转阴。结论：化疗及ＢＭＴ均可使患者融合基因转阴，ａｌｏ－ＢＭＴ似乎能更快地清除体内白血病细胞     

Treatment of acute promyelocytic leukemia with gemtuzumab ozogamicin

Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar biologic features and a unique sensitivity to differentiation therapy with all-trans retinoic acid (ATRA). Modern treatment approaches to APL include simultaneous combination of ATRA and anthracycline-based chemotherapy. Gemtuzumab ozogamicin is a calicheamicin-conjugated monoclonal antibody directed against CD33, a cell surface antigen highly expressed on APL cells. Engagement of CD33 by gemtuzumab results in immunoconjugate internalization and hydrolytic release of calicheamicin, which, in turn, causes irreversible DNA damage and cell death. A number of preliminary reports have highlighted the sensitivity of APL to gemtuzumab given alone or in combination with other agents. Several reasons may account for the efficacy of gemtuzumab in APL, including: (1) CD33 is detectable in virtually 100% of APL cases; (2) calicheamicin belongs to the anthracycline family, a group of chemotherapeutic agents known to be highly effective in APL; and (3) the APL blast cells lack the multidrug resistance glycoprotein 170. Due to the availability of other highly effective agents (ATRA, arsenic trioxide), relatively few APL patients have been treated thus far with gemtuzumab, and their follow-up is still short. However, it is conceivable that the use of this agent in APL will increase in the near future in light of its capability to induce molecular remission even in advanced disease. Furthermore, the use of low doses of gemtuzumab in high-risk patients might be relevant in order to reduce treatment toxicity due to conventional anthracyclines. This review summarizes the mechanism of action and toxicity profile of gemtuzumab as well as the published experience with this compound in patients with newly diagnosed and relapsed APL.     

全反式维甲酸诱导APL细胞分化过程中钙信号途径基因表达水平的变化

为研究钙信号途径在髓系分化中的作用,采用基因芯片技术检测了钙信号途径相关基因在全反式维甲酸(ATRA)诱导急性早幼粒细胞性白血病(APL)细胞株NB4细胞分化过程中的表达情况,并运用实时定量RT-PCR验证基因芯片部分结果,同时检测这些基因在ATRA和8-CPT-cAMP单独和联合作用于NB4-R1细胞和ATRA诱导APL初诊患者原代细胞分化时的表达情况。结果发现:在ATRA诱导NB4细胞分化过程中,许多能直接调节胞内钙离子浓度的基因发生了变化,同时发现许多钙信号途径下游的效应分子的表达上调,并得到实时定量RT-PCR验证。这些基因在ATRA和8-CPT-cAMP单独作用于NB4-R1细胞时变化不大,而在ATRA和8-CPT-cAMP联合作用于NB4-R1细胞分化时与ATRA诱导NB4细胞分化时的表达变化相似。另外,以上基因在ATRA诱导APL初诊患者原代细胞分化的变化情况与诱导NB4细胞分化时相似。结论:钙信号途径可能参与了ATRA诱导的APL细胞分化。     

急性白血病患者血浆TF、TFPI及IL-1β；动态变化分析

本研究旨在探讨血浆组织因子（TF）、组织因子途径抑制物（TFPI）和白介素-1β（IL-1β）在急性白血病（AL）患者病情进展、疗效观察及预后判断中的意义。用酶联免疫吸附方法（ELISA）测定20例健康体检者及24例AL患者化疗前血浆TF、TFPI、和IL-1β的含量，并测定初治AL患者在进行化疗第72小时、缓解3个阶段血浆TF、TFPI、和IL-1β的含量。结果表明：24例初治AL患者首次诱导化疗前血浆TF、TFPI、和IL-1β含量较正常对照组高，差异有显著性（P〈0．01）；化疗第72小时血浆TF和IL-1β含量明显高于首次诱导化疗前，有显著性差异（P〈0．05），但血浆TFPI与化疗前相比明显下降，也有显著性差异（P〈0．01）；24例初治AL患者16例缓解，缓解组血浆TF、TFPI和IL-1β含量降至正常，与正常对照组比无显著性差异（P〉0．05）。结论：TF、TFPI和IL-1β是判断急性白血病患者病情进展、疗效观察及预后的重要指标。     

维 A 酸联合亚砷酸并化疗的序贯疗法治疗急性早幼粒细胞白血病疗效分析

目的研究全反式维A酸(ATRA)联合三氧化二砷(ATO)双诱导缓解方案与单用ATRA诱导缓解方案治疗急性早幼粒细胞性白血病(APL)疗效及副作用的差异,并探讨缓解后采用联合ATRA,ATO和化疗的序贯疗法对患者长期生存的影响。方法回顾性分析2000~2003年采用ATRA单诱导方案和缓解后ATRA/化疗的APL患者和2003~2006年采用双诱导和缓解后序贯治疗的APL患者,统计分析各方案的疗效及副作用。结果ATO和ATRA双诱导与ATRA单诱导方案相比,2者完全缓解(CR)率相似,但双诱导方案明显缩短达到CR所需时间,并缩短患者血小板及凝血参数恢复所需时间,而副作用未增加。CR后采用序贯治疗较ATRA/化疗可明显延长患者无病生存期。结论ATO与ATRA双诱导缓解及缓解后序贯治疗方案较ATRA单诱导及缓解后ATRA/化疗方案治疗APL更为有效。     

Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia: mechanisms of action and resistance,safety and efficacy

Introduction: Acute promyelocytic leukemia (APL) is characterized by peculiar biological features and high sensitivity to therapeutic agents such as anthracyclines, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Because cure rates of up to 80 – 90% have been reported using various combinations of the above agents, future strategies will probably aim at reducing therapy-related toxicity while maintaining therapeutic efficacy. Gemtuzumab ozogamicin (GO) is a calicheamicin-conjugated mAb directed against CD33, a surface antigen highly expressed on APL blasts. GO has been shown to be effective in this disease and better tolerated than conventional chemotherapy.

Areas covered: This review looks at the mechanism of action, pathways associated with resistance and toxicity profile of GO. Reported experience on the use of GO for relapsed or newly diagnosed APL is also discussed along with evidence on its efficacy and relative tolerability in APL management. In addition to its activity in advanced disease, data suggest that GO in various combinations may replace chemotherapy in APL front-line therapy. This should apply in particular to some subsets such as elderly patients or those unfit to receive conventional chemotherapy.

Expert opinion: GO has proven effective and relatively safe as a single agent in advanced APL. In combinations with ATRA and/or ATO, GO may substitute for conventional chemotherapy of APL, particularly in unfit patients.     

全反式维甲酸治疗急性早幼粒细胞白血病并发Sweet''s综合征(附一例报告并文献复习)

目的 讨论并鉴别全反式维甲酸（ATRA）引起的少见的不良反应，提高急性早幼粒细胞白血病（APL）早期治疗的效果。方法 报告国内首例ATRA治疗APL并发Sweet’s综合征的病例，并进行相关文献复习。结果 文献报道共有13例APL患者发生与ATRA治疗相关的Sweet’s综合征。包括本例在内的14例患者，中位年龄49．5（9～84）岁，女10例，男4例。10例患者单独累及皮肤，4例除皮肤外还累及肌肉、肺部、肾脏。皮肤累及以上肢为多（11例），其他部位包括下肢、面部、颈部、背部、腹部、会阴部等。患者出现Sweet’s综合征时，ATRA治疗中位时间为18（6～34）d，外周血中位白细胞计数为7．05（0．80—23．00）×10^9／L。有4例患者未中断ATRA治疗，共有13例患者给予糖皮质激素治疗，12例有效。1例患者自发缓解。在全部14例患者中，有2例出现维甲酸综合征。结论 Sweet’s综合征为ATRA治疗APL患者过程中少见的并发症，与皮肤组织的炎症和感染不易鉴别，其发生的机制与维甲酸综合征之间的关系尚不清楚。糖皮质激素治疗有效，再次应用ATRA后未见复发。     

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初步观察

目的　观察三氧化二砷 (As2 O3 )联合全反式维甲酸 (ATRA)治疗急性早幼粒细胞白血病(APL)的疗效和不良反应。方法　As2 O3 联合ATRA治疗初治和复发APL患者 2 0例 (可评价的患者 18例 )。治疗方法如下 :As2 O3 (0 .1%溶液 ) 10ml加入 5 0g L葡萄糖溶液 5 0 0ml静脉点滴 ,持续 4～ 6h ,1次 d ;ATRA 2 5mg·m- 2 ·d- 1 ,分 2～ 3次服用。结果　 17例患者获得完全缓解 (CR) ,CR率 94.4%。 14例初治患者均获得CR ,4例复发患者中 3例取得CR。均在 30d内达CR。没有发现明显的不良反应。结论　ATRA联合As2 O3 治疗APL患者不仅能获得好的疗效 ,而且能缩短达CR的时间。