去甲氧柔红霉素与柔红霉素方案对初治白血病疗效比较

目的:比较去甲氧柔红霉素(ID)与柔红霉素(DNR)联合阿糖胞苷2种化疗方案对初治急性髓系白血病(AML)的诱导缓解疗效及不良反应。方法:回顾性分析41例初治AML患者应用IDA方案和DA方案治疗的临床资料,比较2组病例的临床疗效、不良反应等指标上的差异。结果:IDA方案组22例中完全缓解(CR)15例,部分缓解(PR)2例,未缓解(NR)5例,有效率77.3%;DA方案组19例中CR6例,PR3例,NR10例,有效率47.4%,2组疗效差异有统计学意义(P<0.05)。IDA组22例中初次完全缓解(CR1)>1年的患者14例(63.6%),DA组19例中CR1>1年的患者7例(36.8%)。2组不良反应差异无统计学意义,主要是较强烈的骨髓抑制。结论:IDA组与DA组治疗初治AML疗效差异有统计学意义,不良反应差异无统计学意义,疗程中支持治疗非常重要。     

去甲氧柔红霉素联合HA方案治疗急性髓细胞白血病初治患者的临床观察

目的:探讨去甲氧柔红霉素(IDA)联合HA方案[(高三尖杉酯碱(HH)加阿糖胞苷(Ara-C)]治疗初发急性髓细胞白血病(AML)的疗效和不良反应。方法:14例AML患者,年龄17～62岁(中位年龄40岁),男8例,女6例,均为初治AML病例。诱导方案为IDA10mg/d,第1～3天,HH3mg/d第1～7天,Ara-C100mg.m-2.d-1第1～7天,静脉滴注。结果:总有效率92.9(13/14),完全缓解率78.6(11/14),治疗过程中未发生早期死亡。化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非造血系统不良反应。结论:IDA联合HA方案为初治AML的高效、安全的方案。     

去甲氧柔红霉素与柔红霉素治疗老年急性非淋巴细胞白血病的疗效比较

<正>与年轻急性非淋巴细胞白血病(ANLL)患者相比,老年ANLL患者由于年龄、身体等因素,无法进行造血干细胞移植治疗,并且往往无法耐受常规剂量的联合化疗,同时容易发生严重的感染、出血、肝肾衰竭等并发症,因此预后相对较差,完全缓解率较低〔1〕,因此有必要寻找疗效好且易耐受的针对老年ANLL的诱导缓解方案。去甲氧柔红霉素(IDA)是由柔红霉素(DRN)衍生的一种新型蒽环类药物,其抗肿瘤效果、亲脂性以及半衰期显著优于DRN。已有报道表明IDA治疗ANLL可以获得较高的缓解率〔2〕。本研究回顾性分析接受IDA+Ara-C(IA)方案和DNR+Ara-C(DA)治疗老年ANLL的疗效及其对预后的影响。     

标准剂量去甲氧柔红霉素联合阿糖胞苷治疗急性髓细胞白血病

目的:探讨标准剂量的去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)治疗急性髓细胞白血病(AML)的疗效和不良反应。方法:14例AML患者,年龄13～70岁(中位年龄36岁),男8例,女6例。初治AML10例,难治、复发AML4例。所有患者均在治疗前进行染色体核型分析,4例染色体异常。诱导方案为IDA 12 mg·m-2·d-1,第1～3天,Ara-C 100 mg·m-2·d-1,持续静脉点滴,第1～7天。结果:1个疗程结束后总有效率92．9％(13／14),完全缓解率85．7％(12／14),其中初治AML的CR率为90．0％(9／10),复发、难治AML的CR率为75．0％(3／4),3例染色体异常患者达细胞遗传学缓解,未发生早期死亡。化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非造血系统不良反应。结论:标准剂量的IDA联合Ara-C 24 h持续静脉点滴,为初治、复发难治AML的高效、安全的方案。     

减低剂量IA方案治疗老年急性髓细胞白血病患者的疗效观察

目的:探讨减低剂量去甲氧柔红霉素联合阿糖胞苷(IA)方案治疗老年急性髓细胞白血病(AML)患者的疗效和不良反应.方法:42例老年AML患者分别以减低剂量IA方案、标准剂量IA方案和标准剂量米托蒽醌联合阿糖胞苷方案(MA)治疗,比较3组病例在临床疗效、不良反应、病死率等指标上的差异.结果:减低剂量IA组完全缓解(CR)6...     

去甲氧柔红霉素联合方案补救治疗难治复发性急性白血病

目的：探讨使用去甲氧柔红霉素为主联合化疗方案补救治疗难治、复发性急性白血病（AL）的疗效及不良反应。方法：急性非淋巴细胞白血病（ANLL）患者及慢性粒细胞白血病患者，采用IA方案治疗，急性淋巴细胞白血病（ALL）患者使用VILP方案治疗。结果：29例患者完全缓解13例、部分缓解5例，完全缓解率44．8％．部分缓解率17．2％，总有效率62．0％。全部患者均出现骨髓抑制，血象最低时间为用药后第10～30天，第19～35天恢复，绝大部分患者出现消化道反应，2例出现心脏毒性，死亡原因为严重感染及出血。结论：去甲氧柔红霉素为主的联合化疗方案是治疗难治、复发性AL的有效药物，临床应注意加强支持治疗、注意环境保护，以降低并发症导致的死亡率。     

预激方案和标准方案治疗初治急性髓系白血病的临床观察

目的:比较预激方案与标准化学治疗(化疗)方案治疗初治急性髓系白血病(AML)的疗效、不良反应和生存情况。方法:回顾性分析175例可随访的初治AML患者,分成预激方案组(n=60)和标准方案组(n=115),标准方案组采用IA(去甲氧柔红霉素、阿糖胞苷)或DA(柔红霉素、阿糖胞苷),预激方案组采用CAG(阿克拉霉素、阿糖胞苷和粒细胞集落刺激因子)或IAG(去甲氧柔红霉素、阿糖胞苷和粒细胞集落刺激因子)诱导治疗,2组患者均为一疗程缓解,同方案巩固2个疗程,或2个疗程缓解,同方案巩固一疗程,随后进入巩固维持治疗阶段。结果:预激方案组与标准方案组在完全缓解率、无病生存率和总生存率方面差异无统计学意义(均P0.05),但预激方案组患者化疗后骨髓恢复时间、感染发生率及单采血小板的输注量均低于标准方案组患者(均P0.05)。结论:预激方案在治疗初治AML的临床疗效和患者生存情况与标准方案相类似,但骨髓抑制及感染发生等不良反应较标准方案轻微,故可作为初治AML患者诱导治疗的可选方案之一。     

去甲氧柔红霉素治疗急性髓系白血病疗效的Meta分析

目的:评价去甲氧柔红霉素治疗急性髓系白血病(AML)的疗效与安全性。方法:采用Cochrane系统评价方法,计算机检索筛选获取所有去甲氧柔红霉素治疗初诊AML的随机对照试验(RCT)文献,评价纳入研究的方法学质量并进行资料提取后,采用RevMan 5.2软件进行Meta分析。结果:共纳入9项RCT研究。Meta分析结果显示:1去甲氧柔红霉素组与柔红霉素组比较,二者完全缓解率虽差异无统计学意义(P=0.120),但前者可明显降低患者耐药率(P=0.006)及复发率(P=0.020),提高患者总生存率(P=0.007)及无病生存率(P=0.005);2去甲氧柔红霉素组与米托蒽醌组比较,二者完全缓解率、耐药率、复发率、总生存率、无病生存率均差异无统计学意义;33组化疗药物不良反应率均差异无统计学意义。结论:初诊AML患者诱导缓解治疗,去甲氧柔红霉素为主的联合化疗方案与米托蒽醌组疗效及安全性均无差异,但疗效均优于柔红霉素。     

去甲氧柔红霉素与预激方案联合治疗首发性老年急性髓细胞白血病的疗效

目的探讨去甲氧柔红霉素(IDA)与预激方案(CAG)联合治疗首发性老年急性髓细胞白血病(AML)的临床效果。方法收集该院2008年6月到2012年1月收治的AML患者80例,按照随机数字表法分为观察组和对照组,每组40例,均给予相应的支持治疗,观察组给予IDA与CAG方案联合治疗,对照组给予柔红霉素(DA)方案治疗,观察两组治疗效果、生存时间及不良反应。结果观察组治疗有效率为92.5%,控制率为97.5%,高于对照组的67.5%,82.5%(P0.05)。观察组平均生存时间高于对照组(P0.05),观察组1、2、3年生存率分别为84.6%、58.9%、41.8%,明显高于对照组的61.0%、36.8%、26.4%(均P0.05)。两组血红蛋白减少、血小板减少、恶性、呕吐、肾功能异常、骨髓抑制时间具有统计学差异(P0.05),肺部感染、直肠、膀胱炎、肝功能损害无统计学差异(P0.05)。结论 IDA与CAG联合治疗首发性老年AML效果显著,毒副反应少,具有一定安全性。     

去甲氧柔红霉素和柔红霉素分别联用阿糖胞苷治疗初诊成人急性髓性白血病的随机比较试验结果

柔红霉素(DNR)去掉发色基环第4位的甲氧基后即为去甲氧柔红霉素(IDR)。IDR 单独或与阿糖胞苷(Ara-C)联合治疗成人急性髓性白血病(AML)的效果已得到肯定。作者对 IDR联合 Ara-C(IDR/Ara-C)和 DNR 联合 Ara-C(DNR/Ara-C)治疗初诊成人 AML 患者进行随机比较研究,以进一步明确 IDR/Ara-C 的临床     

FLAG-IDA方案可改善高危急性髓细胞性白血病患者初始诱导缓解治疗的疗效

目的: 分析高危急性髓细胞性白血病（AML）患者采用FLAG-IDA方案 [甲氧柔红霉素（IDA）联合氟达拉滨（Flu）、阿糖胞苷（Ara-C）和粒细胞集落刺激因子（G-CSF）]进行初始诱导缓解治疗的临床疗效及预后。方法：将2010年1月至2017年1月廊坊市中医医院急诊科诊治的80例AML患者纳入研究，采用随机数字表法将患者分为FLAG-IDA组（41例）和对照组（39例），FLAG-IDA组予甲氧柔红霉素、氟达拉滨、阿糖胞苷及粒细胞集落刺激因子进行初始诱导缓解治疗，对照组予甲氧柔红霉素联合阿糖胞苷组成的IA/DA（3+7）方案进行初始诱导缓解治疗，记录患者治疗过程中出现的不良反应，比较2组患者在第一次诱导治疗结束后的临床疗效，并在患者第一次初始诱导缓解治疗结束后对患者进行为期24个月的随访，记录患者疾病复发或进展情况，比较2组临床疗效及预后。结果：FLAG-IDA组第一次诱导治疗后的完全缓解率、总有效率、总生存率及无病生存率明显高于对照组，未缓解率明显低于对照组（P均＜0.05）；2组部分缓解率及总不良反应发生率比较，差异无明显统计学意义（P均＞0.05）。结论：FLAG-IDA方案用于高危AML患者初始诱导缓解治疗具有较好的临床疗效，且近期总生存率及无病生存率较高，无严重不良反应。     

FLAG方案再诱导化疗急性髓细胞白血病临床观察

目的:初步探讨氟达拉滨(FDR)、高剂量阿糖胞苷(Ara-C)和粒细胞集落刺激因子(G-CSF)即FLAG方案在急性髓细胞白血病(AML)再诱导化疗中的疗效及不良反应。方法:12例经标准HA、DA、MA或IA方案化疗1疗程后未达完全缓解(CR)、骨髓原始细胞下降低于60%的AML患者,予FLAG方案再诱导化疗,即FDR30mg.m-2.d-1静脉滴注,d1～5;Ara-C1g/m2,静脉滴注,每12h1次,d1～5;G-CSF300μg/d皮下注射,第0天开始至白细胞恢复正常。结果:9例(75%)患者获得CR,3例(25%)患者获得部分缓解(PR)。主要不良反应为骨髓抑制,非血液学不良反应不明显。结论:FLAG方案再诱导化疗AML耐受性较好,有效率较高,不良反应可耐受。     

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60‐65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.     

米托蒽醌为主的化疗方案对CD34+高表达急性髓细胞性白血病疗效观察

目的：探索米托蒽醌(MTZ)在急性髓细胞性白血病(AML)化疗中的作用特点，提高AML的疗效和无病生存率(FDS)。方法：80例免疫分型中有CD34^ 抗原高表达的AML，随机选择(MA／MAE、DA／DAE和HA／HAE)方案，联合化疗1～2个疗程后分别比较CR率、骨髓抑制及其它毒副作用；同时对白血病细胞进行体外药物杀伤效应实验，分别比较MTZ、柔红霉素(DNR)、高三尖杉酯碱(HHT)对白血病细胞不同分化阶段的抑制作用。结果：CD34抗原高表达的AML中，1～2个疗程CR率，以MA／MAE方案最高。为80．0％(24／30)．白血病细胞体外药物杀伤实验显示，MTZ对CD34^ 高表达的AML的抑制显著高于DNR和HHT。结论：MTZ具有较强的抗AML活性，临床骨髓抑制明显上述特点可能与其主要作用于AML白血病细胞的分化较早阶段有关。     

Etoposide in remission induction of adult acute myeloid leukemia

96 consecutive acute myelogenous leukemia (AML) patients were analyzed retrospectively with regard to the regimen used for remission induction. 35 patients received daunorubicin for 3 days, cytosine arabinoside and 6-thioguanine for 7 days. 61 were treated with the same regimen but 6-thioguanine was replaced by etoposide. Complete remission was achieved in 57 and 72% of patients, respectively (p = 0.06). In leukemias with monocytic phenotype (M4-M5), the remission rate was significantly higher with the etoposide-containing regimen (p = 0.02). Our findings suggest that the replacement of thioguanine by etoposide could be useful in induction therapy of AML.     

A multicenter,open, non-comparative,phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine,and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG)

OBJECTIVES: To evaluate the efficacy and toxicity of cladribine (2-chlorodeoxyadenosine, 2-CdA), cytarabine (Ara-C), and granulocyte-colony stimulating factor (G-CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study. METHODS: The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C2 g/m2, and G-CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara-C, mitoxantrone or idarubicine, with or without 2-CdA. RESULTS: Fifty-eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara-C as the first-line induction therapy (DA-7), 10 received additional 2-CdA (DAC-7). The CR rates after CLAG were 58% and 10%, respectively in each group (P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease-free survival (DFS, 1 yr) was 29%. Only first-line induction treatment with DA-7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS. CONCLUSION: CLAG regimen has significant anti-leukemic activity and an acceptable toxicity in refractory AML. The addition of 2-CdA to the first-line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.     

A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia

The feasibility of combining gemtuzumab ozogamicin (GO) with intensive chemotherapy as first-line treatment of acute myeloid leukemia (AML) was assessed in 72 patients, aged 17 to 59 years, as a prelude to the United Kingdom Medical Research Council (MRC) AML15 trial. Sixty-four patients received induction chemotherapy (DAT [daunorubicin, ara-C, thioguanine], DA [daunorubicin, ara-C], or FLAG-Ida [fludarabine, ara-C, G-CSF, idarubicin]) with GO on day 1. It was possible to give GO 3 mg/m2 with course 1, but 6 mg/m2 with course 1 or GO in a dose of 3 mg/m2 with consecutive courses was not feasible because of hepatotoxicity and delayed hematopoietic recovery. Thirty-one patients who were treated in consolidation with MACE (amsacrine, ara-C, etoposide) or HidAC (HidAC) and GO (3 mg/m2), and 23 in induction and consolidation, tolerated GO (3 mg/m2) well. Grade 4 liver toxicity and sinusoidal obstructive syndrome was more common in thioguanine-containing schedules (P =.007). Remission with course 1 was seen in 86% of patients. DA or FLAG-Ida with GO in induction achieved complete remission in 91% of patients and 78% of these patients are in continuous complete remission at 8 months. GO given with induction (DA or FLAG-Ida) and consolidation (MACE or HidAC) was well tolerated. These schedules are now being compared in the MRC AML15 trial in patients younger than 60 years.     

P-Glycoprotein Expression in Acute Myeloid Leukaemia Cells at Diagnosis: Its relationship to Daunorubicin or Idarubicin Induction Therapy and Survival

We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo diagnosed acute myeloid leukaemia (AML) and the relationship between presence of P-gp in leukaemic cells and efficacy, as remission induction and survival rate, of two different anthracyclines, daunorubicin (DNR) and idarubicin (IDR).

We found that 30 out of 50 patients (60%) were negative (Group 1) and 20 (40%) were positive (Group 2) for P-gp expression evaluated by mean of MRK16 MoAb using a cut-off of 10% positive cells. Thirty-five out of 50 patients (70%) obtained complete remission (CR); depending on P-gp expression, the CR rate was 80% for group 1 and 45% for group 2 (p lt; 0.005).

The median duration of overall survival was 20 months for patients in Group 1 as compared with 10 months for patients of Group 2 (p < 0.005).

Regarding the anthracycline used, no significant difference in CR was observed in patients of Group 1 (75% of CR with DNR vs. 90% with IDR); Group 2 obtained 40% of CR with DNR vs. 70% with IDR (p < 0.005). The median duration of overall survival (OS) with the two regimens was comparable in Group 1, while it was significantly longer in patients of Group 2 treated with IDR compared with DNR regimen (p < 0.005).

These results confirm the prognostic value of P-gp expression in AML at first appearance and we suggest that idarubicin could be a valid anthracycline drug in the treatment of AML to be evaluated as potential drug of choice in patients with primary or drug-induced multidrug resistance.     

粒细胞集落刺激因子的应用对急性白血病患者预后的影响

目的观察粒细胞集落刺激因子(GCSF)的应用对急性白血病(AL)患者预后的可能影响。方法回顾性研究171例可评价AL患者。分别采用χ2、Cox回归、KaplanMeier等方法分析1疗程完全缓解(CR)率、总CR率、治疗有效率、化疗后WBC减少时间、CR期、生存期及其影响因素;采用等级相关分析GCSF用量与CR期及生存期的关系。急性髓系白血病(AML)患者交替采用以柔红霉素 阿糖胞苷(DA)或高三尖杉酯碱 阿糖胞苷(HA)或米托蒽醌 阿糖胞苷(MA)为主的方案进行诱导缓解和缓解后治疗。急性淋巴细胞白血病(ALL)患者交替采用以长春新碱 柔红霉素 泼尼松(VDP)或长春新碱 阿霉素 泼尼松(VAP)或长春新碱 米托蒽醌 泼尼松(VMP)或环磷酰胺 长春新碱 柔红霉素 泼尼松(CODP)为主的方案进行诱导缓解和缓解后治疗。用药组均在患者WBC<1.0×109/L时予以重组人GCSF(rhGCSF)(1.5～6.0μg·kg-1·d-1),一般WBC达2.5×109/L时停用。结果(1)AL患者化疗后应用GCSF可使化疗后WBC减少时间明显缩短;但不影响患者的1疗程CR率、CR率和治疗有效率;(2)使用GCSF不影响ALL患者CR期,但明显缩短AML患者CR期;(3)使用GCSF不影响ALL患者的生存期,但缩短AML患者的生存期;(4)尚未发现使用GCSF的AML患者中因子用量多少与CR期及生存期存在相关关系。结论AML患者必须非常慎用GCSF。     

Contrasting in vitro effects for the combination of fludarabine, cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (FLAG) compared with daunorubicin and Ara-C in P-glycoprotein-positive and P-glycoprotein-negative acute myeloblastic leukaemia

It has been suggested that the FLAG remission induction regimen comprising fludarabine (F-ara), cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (G-CSF) may be capable of overcoming P-glycoprotein (P-gp)-related multidrug resistance (MDR) in patients with acute myeloblastic leukaemia (AML). We have investigated the in vitro response of P-gp-positive and -negative AML clones to FLAG and compared this with their response to treatment with Ara-C and daunorubicin (DNR). Twenty-four cryopreserved samples from patients with AML were studied using a flow cytometric technique for the enumeration of viable (7-amino actinomycin D negative) cells. Samples consisted of 12 P-gp-positive and 12 P-gp-negative cases, as measured by the MRK16 antibody. The results were analysed by calculating the comparative drug resistance (CDR), i.e. the percentage cell death caused by Ara-C + DNR subtracted from the percentage cell death, caused by FLAG after 48 h incubation in suspension culture. P-gp-positive clones were shown to have a significantly higher CDR than P-gp-negative clones (P = 0. 001). Furthermore, a significant positive correlation (r2 = 0.40, P < 0.01) was found between P-gp protein expression and CDR. However, P-gp function, measured using cyclosporin modulation of rhodamine 123 (R123) uptake, was not associated with the CDR, demonstrating that there are other properties of P-gp, besides its role in drug efflux, that modulate the responsiveness of AML blasts to chemotherapy. These results are consistent with a potential benefit for FLAG in P-gp-positive AML, but not P-gp-negative AML, compared with standard anthracycline and Ara-C therapy.