维甲酸联合三氧化二砷及小剂量HA方案治疗急性早幼粒细胞白血病25例分析

2002年12月～2007年12月我们用全反式维甲酸（ATRA）、三氧化二砷（As2O3）与小剂量HA方案化疗联合治疗急性早幼粒细胞白血病（APL）25例，现报道如下。     

全反式维甲酸联合三氧化二砷治疗急性早幼粒细胞白血病疗效观察

目的观察全反式维甲酸（ATRA）联合三氧化二砷（As2O3）治疗初发急性早幼粒细胞白血病（APL）的疗效和不良反应。方法25例初发APL患者，采用ATRA联合As2O3治疗。用药方法：ATRA A30-60mg／d；0．1％As2O3注射液10ml溶解于5％葡萄糖注射液500ml中，持续静脉滴注4-5h，1次/d，28d为1个疗程。观察完全缓解率、获得完全缓解的时间、不良反应等。结果25例初发APL患者早期死亡2例，23例获完全缓解，完全缓解率为92％；获得完全缓解的平均时间为（25．5±4．5）d；15例（60％）患者在治疗开始后出现WBC升高，调整ATRA和As2O3的剂量后均能恢复；10例（40％）患者出现轻度肝功能异常，经调整剂量及应用护肝药物后均能恢复。随访至2005年12月（4-28个月），23例获完全缓解的患者无一例复发。结论ATRA联合As2O3治疗初发APL疗效好，不良反应少，而且能缩短达完全缓解的时间。     

全反式维甲酸、三氧化二砷治疗急性早幼粒细胞白血病疗效分析

目的观察全反式维甲酸(ATRA)、三氧化二砷(As2O3)治疗急性早幼粒细胞白血病(APL)的临床疗效。方法将39例APL患者随机分为两组,分别应用ATRA、As2O3诱导治疗,完全缓解(CR)后给予联合化疗、ATRA及As2O3序贯治疗。结果ATRA组和As2O3组CR率分别为79%和90%(P>0.05)。两组高白细胞综合症发生率分别为52.6%和40%(P>0.05)。ATRA组6例DIC死亡4例,As2O3组6例DIC死亡1例。As2O3治疗4例复发APL达CR3例。结论ATRA、As2O3治疗APL的CR率及高白细胞综合症的发生率无差异,As2O3治疗复发APL及ATRA耐药的患者疗效好,可降低APL合并DIC患者的死亡率,以联合化疗、ATRA与As2O3序贯治疗作为APL达CR后的巩固强化治疗手段是可行的。     

全反式维甲酸联合三氧化二砷治疗急性早幼粒细胞白血病疗效观察

目的观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗初发急性早幼粒细胞白血病(APL)的疗效和不良反应。方法25例初发APL患者,采用ATRA联合As2O3治疗。用药方法:ATRA30～60mg/d;0.1%As2O3注射液10ml溶解于5%葡萄糖注射液500ml中,持续静脉滴注4～5h,1次/d,28d为1个疗程。观察完全缓解率、获得完全缓解的时间、不良反应等。结果25例初发APL患者早期死亡2例,23例获完全缓解,完全缓解率为92%;获得完全缓解的平均时间为(25.5±4.5)d;15例(60%)患者在治疗开始后出现WBC升高,调整ATRA和As2O3的剂量后均能恢复;10例(40%)患者出现轻度肝功能异常,经调整剂量及应用护肝药物后均能恢复。随访至2005年12月(4～28个月),23例获完全缓解的患者无一例复发。结论ATRA联合As2O3治疗初发APL疗效好,不良反应少,而且能缩短达完全缓解的时间。     

急性早幼粒细胞白血病的联合治疗方法

2004年1月至2007年5月我院采用全反式维甲酸(ATRA)联合三氧化二砷(AS2O3)治疗急性早幼粒细胞白血病(APL)26例,取得较好的效果,现报告如下.     

维甲酸加化疗和小剂量肝素治疗急性早幼粒细胞白血病15例临床观察

目的总结维甲酸、化疗、小剂量肝素合用治疗急性早幼粒细胞白血病（APL）并预防弥漫性血管内凝血（DIC）的疗效。方法15例APL患者,采用全反式维甲酸（ATRA）、适量化疗诱导分化至完全缓解（CR）,同时予以小剂量肝素。结果APL的完全缓解率达86．7％,平均缓解时间达37．4d,无一例DIC发生。结论维甲酸、化疗、小剂量肝素合用治疗急性早幼粒细胞白血病并预防DIC效果满意。     

三氧化二砷治疗复发性急性早幼粒细胞白血病的疗效研究

目的　观察三氧化二砷 (As2 O3)治疗复发性急性早幼粒细胞白血病 (APL)的临床疗效。方法　总结和临床观察 2 8例复发性APL患者的临床特点、随访 8年。结果　 2 8例中的 2 3例获得完全缓解 (CR) ,CR率为 82 .1%。 6例维持治疗 8个月失去随访 ;8例CR后 1年复发放弃治疗 ;2例CR4 分别为 3.5个月、5个月再复发合并颅内出血而死亡。 7例仍存活。结论　As2 O3治疗复发性APL的CR率高 ,不良反应轻 ,与全反式维甲酸 (ATRA)和其他化疗药物无交叉耐药现象 ,适合用于耐ATRA的病例和经As2 O3诱导缓解后复发病例 ,并可用于维持治疗。     

全反氏维甲酸、联合三氧化二砷及联合化疗治疗急性早幼粒细胞性白血病12例疗效观察

急性早幼粒细胞性自血病（APL）是起病凶险部分患者可以治愈的一种自血病亚型，全反氏维甲酸（ATRA）或三氧化二砷（As2O3）的临床应用，使APL患者的早期死亡率明显降低，完全缓解率（CR）显著提高。大宗病例的研究结果显示ATRA合用或不合用化疗的CR牢已高达92％～95％。五年存活率已达60％～70％。但以上治疗方案都未能根除APL白血病细胞克隆，仍有60％左右患者最终复发。如何发挥现有药物的作用．提高缓解率和长期生存率，是医务人员关注的问题．2002年以来．我们采取ATRA、联合As2O3及联合细胞毒药物治疗APL12例，取得了良好的效果，现报告如下：     

三氧化二砷、维甲酸联合化疗序贯治疗对急性早幼粒细胞白血病的长期疗效

目的总结三氧化二砷（As2O3）、全反式维甲酸（ATRA）及化疗的序贯巩固方案对急性早幼粒细胞白血病（APL）的远期疗效。方法对我院1996～2006年间诊断为APL的40例患者,缓解后用序贯方案进行巩固治疗的24例,回顾性地与单用维甲酸进行巩固治疗的16例作比较,随访时间至少超过5年,评价两组间的复发率及5年无病生存率的差异。结果接受序贯巩固治疗患者的复发率仅4%,单用维甲酸组复发率为26.6%,5年生存率两组分别为96%及81%。结论接受序贯巩固方案有利于减低APL的复发率,提高患者的5年无病生存率。     

42例急性早幼粒细胞白血病患者的治疗方案和疗效分析

目的探讨急性早幼粒细胞性白血病的治疗方案及疗效。方法将本院血液内科收治的急性早幼粒细胞白血病患者共42例,平均分为3组,采用不同化疗方案治疗,A组单独使用全反式维甲酸诱导治疗,B组应用全反式维甲酸和三氧化二砷诱导治疗,C组应用全反式维甲酸联合柔红霉素诱导治疗,比较3组的疗效和副作用。结果3组患者的一般情况和实验室检查结果比较差异无统计学意义。B、C组患者的治疗效果优于A组,3组均出现不同程度的副作用,经比较差异无统计学意义。结论全反式维甲酸联合三氧化二砷、全反式维甲酸联合柔红霉素组两种联合治疗方案优于全反式维甲酸单独治疗方案,对急性早幼粒细胞白血病应该使用联合治疗。     

Pharmacokinetics of low-dose all-trans retinoic acid in Japanese children with cancer

All-trans retinoic acid (ATRA) is used as differentiation therapy for acute promyelocytic leukemia (APL). The two major adverse effects of ATRA therapy are hyperleukocytosis and retinoic acid syndrome. In order to prevent these adverse effects, low-dose ATRA therapy (25 mg/m2/d) has been tried in adults. Accordingly we assessed the pharmacokinetics of low-dose ATRA in children with cancer. Four children (one with APL and three with other advanced cancer) were administered ATRA and its pharmacokinetics were evaluated. In three patients, the pharmacokinetic parameters of ATRA were similar to those previously determined for APL patients in remission, but the values were lower in one patient. Low-dose ATRA was effective for APL, but not for the solid tumors. This therapy did not cause any severe toxicity. Further studies are needed to determine the optimum ATRA regimen and to evaluate low-dose ATRA combined with chemotherapy in children with APL.     

应用流式细胞技术(FCM)检测儿童APL微小残留病

目的研究应用流式细胞技术(FCM)检测APL病人的白血病微小残留病(MRD),评价其临床意义。方法应用FCM检测和分析36例APL病儿在初发期和完全缓解期的CD13、CD33、CD34和TdT表达,全部APL病人每日输入AS2O3治疗,直到完全缓解(CR)。结果36例APL病人在初发期CD13、CD33表达均明显高于对照组(P<0.05),其阳性表达率分别为63.88%(23/36)和80.55%(29/36),CD34和TdT均为低表达,经AS2O3治疗的CR期有34例APL病人CD13和CD34阳性细胞为10‰左右,其余2例仍为高表达(CD13和CD33抗原阳性细胞>10%~20%),并于3个月内复发。结论研究结果推断,应用FCM检测APL病人CD13和CD33表达可预测复发,FCM分析结果可提高检测MRD的敏感性并可估计APL病人的预后,CD13和CD33双表达可能预后不良。     

三氧化二砷联合全反式维甲酸对人卵巢癌细胞的抑制作用

目的:探讨三氧化二砷(AS2O3)联合全反式维甲酸(ATRA)对人浆液性卵巢癌细胞株SKOV3的抑制作用及其机制。方法;四甲基偶氮唑蓝光吸收法(MTT)、流式细胞术及免疫荧光法检测体外培养的SKOV3细胞在AS2O3单独作用及联合ATRA作用下对卵巢癌细胞生长的抑制及促凋亡作用。结果:单用ATRA对SKOV3细胞的生长无影响;单用AS2O3可以抑制SKOV3细胞的生长;联合使用AS2O3和ATRA较单用AS2O3对SKOV3细胞的抑制作用强(P<0.05);流式细胞术证实:5.0μmol/LAS2O3联合1.0μmol/LATRA作用48h时,SKOV3细胞出现G2/M期阻滞增强、S期减低(P<0.05);AnnffxinV染色检测到早期凋亡细胞增多,晚期凋亡及继发性坏死细胞减低(P<0.05)。结论:AS2O3能上调SKOV3细胞中细胞周期抑制蛋白P27的表达,ATRA联合AS2O3可以增强上述效应。故ATRA对诱导SKOV3细胞凋亡有增敏效应,该效应过程可能依赖于细胞周期负性调控因子P27蛋白的过度表达。     

Pseudotumor cerebri with all-trans retinoic acid. A case report

The diagnosis of pseudotumor cerebri (PC) is based on the triad of: (1) papilledema, (2) elevated intracranial pressure with a normal cerebrospinal constituency and (3) normal central nervous system imaging studies. It is an uncommon complication of all-trans-retinoic acid (ATRA) therapy in children treated for acute promyelocytic leukaemia (APL). Its occurrence is rare among adult patients with APL and treated with ATRA . We report a case of an adult with APL who developed PC during induction therapy with ATRA-PC was managed with repeated lumbar punctures and corticotherapy.     

Treatment of acute promyelocytic leukemia: a single institution experience

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.     

Therapeutic results with apl 93 protocol in acute promyelocytic leukemia (34 cases)

BACKGROUND: Acute promyelocytic leukaemia (APL) account for approximately 10% to 15% of all AML in most reports. Clinical features includes the presence in 80% to 90% of patients of a severe hemorrhagic syndrome, a specific balanced translocation between chromosomes 15 and 17 with a fusion of a large pert of the retinoic acid receptor a gene (RARa) on chromosome 17 to a part of the promyelocytic leukaemia (PML) gene on chromosome 15.More than 75% of patients (under 65 years of age) can be cured, with the application of a combination of anthracyclines and all-trans retinoic acid (ATRA), followed by maintenance therapy. AIM: of the study was to assess of the therapeutic management of APL 93 protocol in acute promyelocytic leukemia. METHODS: We present here the results of a retrospective study concerning 34 patients with APL included between 1998 and 2004 in the APL 93 protocol : 20 in group B and 14 in group C. CR was 82 %. RESULTS: Failure is only due to toxic death (18%) Event free survival at 4 years is 63,47% with relapse rate at 14.25%. Overall survival at 4 years is 69,72%. Our results are acceptable and can be improved with reduction of failure due to toxic death, probably with omission of cytarabine from induction and consolidation adapted by the Spanish PETHEMA Group.     

儿童感染相关噬血细胞综合征继发急性早幼粒细胞白血病一例并文献复习

 目的 探讨噬血细胞综合征(HLH)治疗后继发急性早幼粒细胞白血病(APL)的临床特征及预后。方法 收集1例表皮短杆菌感染相关HLH患儿在接受依托泊苷(VP16)治疗后继发APL的临床资料,并结合国内外报道的17例病例进行文献复习。结果 某院收治1例表皮短杆菌感染相关HLH,接受HLH-04方案治疗后继发APL,给予化疗后APL缓解并存活。复习文献纳入17例HLH治疗后继发白血病病例,共18例:男性13例,女性5例,首次诊断HLH年龄为0~19岁,中位年龄为3岁,HLH类型中EB病毒感染相关HLH (EBV-HLH)占61%,VP16累积剂量为400~20 500 mg/m²,中位数为3 100 mg/m²;继发白血病潜伏时间为6~72个月,中位时间为26个月。18例患者中死亡6例,存活12例,其中6例M3接受化疗后均完全缓解并存活。结论 感染相关HLH是HLH继发白血病中较常见的原发病类型,在继发白血病中,以APL发生率较高。在HLH治疗期间,需要关注VP16累积剂量、应用频率、联合方案以及患者个体差异等情况,骨髓的分子生物学有助于监测继发白血病的发生。     

Arsenic trioxide, a new drug for the treatment of acute promyelocytic leukemia resistant to tretinoine]

Chinese clinical investigators in 1986 demonstrated the therapeutic potential of tretinoin and in 1992 that of arsenic trioxide in the treatment of acute promyelocytic leukaemia. These observations have been confirmed in European and American centres. In acute promyelocytic leukaemia there is an abnormal receptor for retinoids, designated PML/RAR-alpha. This receptor binds retinoids inadequately so that extra retinoids (in the form of tretinoin) are required to restart the normal cellular maturation, after which the promyelocytes can mature into granulocytes. Arsenic trioxide has a different mode of action, possibly related to its effects on sulfhydryl-rich proteins, resulting in dysplastic leukaemic promyelocytes, ending up in apoptotic cell death. Since 1990 tretinoin has been included worldwide in the treatment of acute promyelocytic leukaemia. The use of arsenic trioxide has not yet been included in treatment protocols for promyelocytic leukaemia in western medicine.