复方青黛片治疗难治性、复发性急性早幼粒细胞白血病(附36例报告)

将71例难治性或复发性急性早幼粒细胞白血病（APL）患者随机分两组,治疗组用复方青黛片治疗,对照组用常规化疗或全反式维甲酸（ATRA）治疗,观察两组临床疗效及骨髓CD34^＋细胞bcl-2表达情况。结果治疗组完全缓解率、部分缓解率明显高于对照组（P均〈0.01）;两组骨髓CD34^＋细胞bcl-2蛋白产物的阳性率和OD值治疗后均降低,但治疗组降低幅度大于对照组（P〈0.01）。提示复方青黛片治疗难治性或复发性APL疗效确切;其机制可能是下调凋亡抑制基因bcl-2表达,诱导或促进骨髓CD34^＋细胞的分化和凋亡。     

全反式维甲酸与三氧化二砷治疗急性早幼粒细胞白血病临床分析

目的:观察全反式维甲酸(ATRA)与三氧化二砷(As2O3 )联合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:As2O3 联合ATRA治疗初治APL患者16 例,As2O3 0.1%注射液10 ml加入5%葡萄糖溶液500 ml静脉点滴,持续4~5 h,1 次/d;ATRA 25 mg·m-2·d-1,分3 次口服,观察CR率、获得CR所需时间、不良反应。结果:15例患者获得完全缓解(CR),CR率93.8%,获得缓解时间(27.3±3.6) d,没有发现明显的不良反应。结论:As2O3 联合ATRA治疗初发APL患者疗效好,能缩短CR的时间,长期CR时间需要进一步观察。     

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)治疗急性早幼粒细胞白血病(APL)的完全缓解(CR)率和不良反应。方法ATRA25mg.m-2.d-1,As2O3(0.1%溶液)10mL/d联合治疗初发APL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ATRA和As2O3的剂量。结果29例初发APL患者,早期死亡2例,27例获得CR,CR率93.1%。获得CR的平均时间为(25.2±3.5)d。没有发现严重不良反应。结论ATRA联合As2O3治疗初发APL疗效好,不良反应患者能耐受。     

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临床观察

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:对联合应用ATRA和As2O3治疗的55例APL患者的完全缓解(CR)率、达CR所需时间、早期病死率和不良反应进行观察,并与单独应用ATRA组31例和As2O3组26例进行比较。联合用药组治疗方法为ATRA25mg·m-2.d-1,As2O30.16mg·kg-1.d-1直至CR,根据外周血白细胞计数、不良反应调整ATRA和As2O3的剂量。结果:联合用药组与单独应用ATRA、As2O3组相比,CR率无统计学意义(分别为96.3%、83.9%、84.6%,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25d、47d、41d,均P<0.05),早期死亡率亦低于单独用药组(分别为3.6%、12.9%、11.5%,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。     

全反式维甲酸治疗急性早幼粒细胞性白血病致Sweet综合征--病例报告及文献复习

目的:提高对全反式维甲酸(ATRA)治疗急性早幼粒细胞性白血病(APL)少见副作用的认识。方法:报告1例ATRA治疗APL致Sweet综合征的病例及治疗过程,并对相关文献进行复习总结。结果:ATRA治疗APL可以导致Sweet's综合征,采用糖皮质激素治疗有效。结论:Sweet综合征是维甲酸的少见副作用,临床上应提高对该综合征的早期诊断。     

亚砷酸联合维甲酸治疗急性早幼粒细胞白血病6年临床观察

目的:观察亚砷酸(AS2O3)联合维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL)的疗效和特点.方法:对APL住院患者随机分为2组,治疗组38例,单纯AS2O3加ATRA,从诱导治疗、巩固治疗到停药观察6年.对照组36例,AS2O3加ATRA加化疗(DA或MA),观察6年.结果:治疗组38例,初治诱导缓解治疗达完全缓解率(CR)为100%.3年复发率为2.6%,6年持续缓解率(CCR)为94.6%.对照组36例初治诱导缓解率为81.3%,3年复发率为30.7%,6年CCR为61.5%.治疗相关不良反应治疗组比对照组较轻而少(P＜0.01),3年治疗相关死亡率为0,而对照组为16.7%(6/36).结论:亚砷酸联合维甲酸治疗APL,具有协同增强作用,疗效高,复发率低,治疗相关不良反应少,未见耐药性产生.     

复方青黛片治疗复发性急性早幼粒细胞白血病疗效观察

总结应用复方青黛片治疗复发性急性早幼粒细胞白血病１２例疗效观察，结果完全缓解率９１．７％，部分缓解率８．３％。认为疗铲优于化疗及全反式维甲酸。     

AIDA方案治疗急性早幼粒细胞白血病分子生物学疗效初步观察

目的：观察全反式维甲酸加去甲氧柔红霉素加阿糖胞苷（AIDA）方案治疗急性早幼粒细胞白血病（APL）患者的分子生物学疗效。方法：在全反式维甲酸（ATRA）诱导缓解后的32例APL患者中,予去甲氧柔红霉素（IDA）加阿糖胞苷巩固化疗2个疗程,治疗前后检测PML／RARα融合基因水平。结果：临床和血液学安全缓解29例（91％）,部分缓解2例（6％）,总有效率97％。分子生物学缓解率达31％,10例转阴者随访1年内连续2次检测基因持续阴性者3例（30％）。结论：AIDA方案是治疗APL达到分子生物学缓解的有效方法;年龄、治疗前白细胞数、ATRA诱导缓解时间及IDA应用的疗程和剂量,是影响APL患者分子生物学缓解的重要因素。     

ATRA、ATO联合小剂量HHT治疗急性早幼粒细胞白血病疗效观察

目的探讨急性早幼粒细胞白血病（APL）的最佳治疗方案。方法将初诊的24例APL患者随机分为观察组13例和对照组11例。观察组予全反式维甲酸（ATRA）、三氧化二砷（ATO）联合小剂量高三尖杉酯碱（HHT）诱导治疗,HA方案巩固治疗2个疗程;对照组予ATRA＋ATO＋柔红霉素（DNR）治疗,DA方案巩固治疗2个疗程。治疗结束比较两组相关指标变化。结果诱导及巩固治疗结束时两组血液学缓解率、PML/RARa融合基因转阴率均无显著差异;观察组累计血浆输注量及血小板输注量、败血症发生率及平均住院费用均明显低于对照组,P均〈0.01。结论 ATRA、ATO联合小剂量HHT治疗初诊APL效果确切;且并发症发生率低,治疗费用少。     

全反式维甲酸治疗急性早幼粒细胞白血病不良反应的护理

全反式维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL)完全缓解率高,不引起骨髓抑制,能改善DIC状态,已被广泛应用.良好的护理可减轻甚至消除ATRA应用过程中产生的不良反应.1993年～2000年,我科共收治初治APL患者52例,出现ATRA治疗相关不良反应71例次,现将护理体会报告如下.……     

原发高白细胞型急性早幼粒细胞白血病66例临床特征及治疗研究

目的探讨原发高白细胞型急性早幼粒细胞白血病(APL)的临床特点及有效的治疗方法。方法回顾性分析1993年10月至2006年8月苏州大学附属第一医院收治的66例原发高白细胞型APL患者和152例非高白细胞型APL患者的临床资料,并对高白细胞型患者按治疗方案的不同进行了分组比较。结果高白细胞组APL患者早期病死率、弥散性血管内凝血(DIC)和维甲酸综合征(RAS)发生率分别为30.3%,57.6%和31.8%,均高于非高白细胞组(7.2%,38.1%和21.1%)(P<0.05),而完全缓解(CR)率较低(63.6%对88.2%)(P<0.05)。高白细胞组患者中61例接受了诱导治疗,其中31例单用维甲酸治疗,21例维甲酸联合亚砷酸治疗,9例单用亚砷酸治疗,各组早期病死率分别为27.3%,14.3%和55.6%,CR率分别为67.7%,81.0%和44.4%。61例患者中41例在接受诱导分化治疗的同时加用化疗,其CR率为80.5%,总病死率为19.5%;而未加用化疗的20例患者其CR率为45.0%,总病死率为55.0%,两组比较差异有显著性意义(P<0.05)。结论原发高白细胞型APL较非高白细胞型APLCR率低,早期病死率高,DIC、RAS发生率高。维甲酸加亚砷酸双诱导并联合小剂量化疗是治疗高白细胞型APL的最有效的方案,可明显减少早期病死率,提高CR率。     

Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia

It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.     

Therapy-related myelodysplastic syndrome-acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem.

The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS-AML). Of these, 3 of 46 (6.5%) patients received front-line chemotherapy with or without ATRA and acquired tMDS-AML while in first remission of APL. Two underwent repeated chemotherapy cycles with ATRA because of APL relapse and acquired tMDS-AML while in the second or third remission of APL. In 2 patients, clinical and biologic characteristics of tMDS-AML were as expected for postalkylating forms (long latency, MDS phase preceding AML, karyotypic aberrations involving chromosomes 5 or 7), even though one of them had not previously received alkylating drugs. Three of the 5 patients died shortly after tMDS-AML diagnosis, one is alive with tMDS, and one is alive and in CR after allogeneic bone marrow transplantation. The occurrence of tMDS-AML after successful therapy for APL is an emerging problem. The availability of prognostic score systems at initial diagnosis and monitoring of residual disease by polymerase chain reaction might allow better tailoring of treatment intensity in APL to spare unnecessary toxicity and to minimize the risk for tMDS-AML in patients who are presumably cured.     

Successful treatment of relapsed and refractory acute promyelocytic leukemia with arsenic trioxide (As2O3)

It has been shown that arsenic trioxide (As2O3) may induce hematologic remissions in patients with acute promyelocytic leukemia (APL) refractory to all-trans retinoic acid (ATRA). We reported on a patient with ATRA and drug-resistant APL that was successfully treated with As2O3. The patient had been given a diagnosis of typical APL and was treated with ATRA and chemotherapy for 12 months. He achieved complete remission (CR), but leukemia relapsed with 43% APL cells in the bone marrow in the 16th month of treatment. ATRA and cytarabine plus daunorubicin were administered; however, the APL cells in the bone marrow increased to 97.2%. As2O3 was initiated intravenously, and bone marrow showed a decrease of APL cells (6.7%) and a partial differentiation after 9 days. The patient received idarubicin (IDA) and steroid pulse because of the development of ATRA-like syndrome, and achieved CR 37 days after the initiation of As2O3. He received an additional 2 courses of As2O3 with IDA, and is in CR. These results demonstrated the therapeutic efficacy of As2O3 in treating ATRA and drug-resistant APL.     

Acute promyelocytic leukemia: All-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA. Am. J. Hematol. 60:87–93, 1999. © 1999 Wiley-Liss, Inc.     

Acute myelogenous leukemia with a t(2;17;4)(p13;q21;p16) aberration: effective treatment with all-trans retinoic acid and granulocyte colony-stimulating factor

The efficacy of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL) has been well documented. However, ATRA is not as effective against other types of acute myelogenous leukemia (AML) or myelodysplastic syndromes. We present a patient with AML (FAB: M2) associated with a t(2;17;4)(p13;q21;p16) chromosomal defect in which the 17q21 breakpoint was not within the retinoic acid receptor alpha locus which is typically rearranged in APL. This patient was successfully treated with ATRA and granulocyte colony-stimulating factor and improvement of hematological parameters lasted for 19 months without the use of cytotoxic agents.     

三联方案治疗初诊急性早幼粒细胞白血病临床效果分析

目的观察全反式维甲酸（ATRA）、亚砷酸（ATO）及柔红霉素（DNR）三联方案治疗急性早幼粒性白血病（APL）的疗效及安全性。方法将61例采用四种不同诱导方案治疗的临床初诊APL患者根据化疗方案不同分为四组,其中采用ATRA＋ATO＋DNR者为观察组、ATO＋DNR者为对照1组、ATRA＋DNR者为对照2组、DNR＋阿糖胞苷（Ara-c）为对照3组,对完全缓解（CR）率、病死率及毒副作用进行回顾性分析。结果观察组CR率显著高于其他三组,病死率显著低于对照3组,高白细胞血症持续时间显著短于对照1、2组,与对照1、2组比较维甲酸综合征（RAS）发生率无明显差异,肝功能损伤（均为可逆性）发生率显著高于其他三组。结论 ATRA、ATO及DNR三联方案治疗初诊APL患者疗效显著,且安全性较高。     

Treatment of older adults with acute promyelocytic leukaemia

Only 15 to 20% of acute promyelocytic leukaemia (APL) patients are older than 60 years, and the characteristics and outcome of APL in that age range are not well known. Published studies show that APL in elderly patients has haematological features similar to those of APL in younger patients. However, using the current combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy, the outcome for these patients, although it has much improved, remains less favourable than that for younger patients. This is due to a higher incidence of early deaths and deaths in complete remission (CR), during consolidation chemotherapy courses, whereas the relapse rate appears similar in older and younger adults.Treatment approaches with more limited myelosuppression, especially consolidation chemotherapy with an anthracycline alone (without Ara-C), low-dose maintenance treatment with 6-mercaptopurine, methotrexate and ATRA, and consolidation with arsenic trioxide, should be tested especially in elderly patients in order to replace more toxic 'classical' anthracycline-Ara-C consolidation treatment, after achieving CR with ATRA.