去甲氧柔红霉素治疗急性髓系白血病的临床观察

目的:观察去甲氧柔红霉素(IDA)与柔红霉素(DNR)、米托蒽醌(MTN)、吡柔比星(THP)治疗急性髓系白血病的疗效和毒副反应。方法:选择我院2005年4月～2010年4月住院的62例急性髓系白血病患者,随机分为2组,治疗组30例采用IDA+阿糖胞苷(Ara-C)治疗,对照组32例采用DNR(或MTN、THP)+Ara-C治疗。结果:治疗组和对照组完全缓解率(CR)分别为80.0%和43.8%,总有效率(RR)分别为93.3%和68.8%,临床严重感染率分别为36.7%和34.4%。2组CR和RR比较,差异有统计学意义(P<0.05),但2组的严重感染率比较,差异无统计学意义(P>0.05)。结论:以IDA组成的联合化疗方案治疗急性髓系白血病疗效较好。     

去甲氧柔红霉素联合Ara-C治疗难治性白血病

目的 :应用去甲氧柔霉素 ( IDA)联合 Ara- C组成的 IA方案治疗难治性白血病观察其疗效。方法 :IDA5 mg/ d～ 10 mg/ d ivgtt连续 3 d,Ara- C10 0 mg/ d～ 2 0 0 mg/ d ivgtt连续 5 d为一疗程。结果 :5例难治性白血病 (急淋 4例 ,急非淋 1例 ) ,采用 IA方案治疗 1个～ 2个疗程后 ,完全缓解 3例 ,部分缓解 2例。结论 :应用 IA方案治疗难治性白血病取得较好疗效 ,主要副作用为骨髓抑制 ,粒细胞减少 ,未发现心、肝、肾毒副作用     

伊达比星加强预处理异基因造血干细胞移植治疗难治性急性髓系白血病的临床研究

 　目的　探讨预处理方案中加伊达比星增强预处理的异基因造血干细胞移植（allo-HSCT）治疗难治性急性髓系白血病的疗效和安全性。方法　选择北京军区总医院血液科2010年8月至2012年12月在预处理方案中增加伊达比星的allo-HSCT治疗的27例难治性急性髓系白血病患者,其中男13例,女14例,年龄2～53岁,平均年龄24.6岁;FAB分型包括M1型1例,M2型10例,M3型1例,M4型1例,M5型11例,M6型3例;移植时复发未缓解18例,复发后取得2次或者3次缓解9例;22例采用骨髓加外周血干细胞联合移植,5例仅采用外周血干细胞移植;预处理方案为在以氟达拉滨替代环磷酰胺的改良白消安＋环磷酰胺方案基础上,加用伊达比星（15 mg／m2,连续用3 d）,移植后观察患者不良反应、并发症和无病生存等情况。结果　全部患者均获重建造血,能较好耐受此预处理方案,无因预处理相关不良反应而早期死亡者,未发生心脏毒性事件,移植后粒细胞植活平均时间为15 d（11～23 d）,植入证据示均为完全供者造血。随访至2013年5月,中位随访时间12个月（5～33个月）,13例发生急性GVHD,11例发生慢性GVHD,因急性GVHD死亡2例,发生严重感染的13例中死亡1例,复发的7例中死亡5例;共死亡8例,其余19例患者生存。全组患者治疗相关死亡率、复发相关死亡率和总体生存率分别为11.1 %（3／27）、18.5 %（5／27）和70.4 %（19／27）。结论　allo-HSCT预处理方案中加入伊达比星的增强方案安全可行,患者耐受良好,可降低难治性白血病的复发率,提高长期生存率,移植后并发症并未增加。     

阿糖胞苷分别联合伊达比星、柔红霉素治疗急性非淋巴细胞白血病成本效果的比较分析

比较伊达比星联合阿糖胞苷（IA组）与柔红霉素联合阿糖胞苷（DA组）治疗成人急性非淋巴细胞白血病的效果、住院总费用并进行成本效果分析。选取了102例成人急性非淋巴细胞白血病患者,分别给予伊达比星联合阿糖胞苷和柔红霉素联合阿糖胞苷的一疗程（3+7）模式治疗,统计治疗效果和住院期间各项费用,结果IA组完全缓解率和有效率均高于DA组（60.00%vs.30.56%,86.67% vs.69.44%）,虽然伊达比星的费用远高于柔红霉素,IA组患者住院总费用显著高于DA组（P<0.05）,但成本效果分析显示IA方案优于DA方案,也就是说在与阿糖胞苷联用时,伊达比星与柔红霉素相比更为有效、经济,值得在临床上推广应用。     

伊达比星加中剂量阿糖胞苷强化疗对急性髓系白血病预后的影响

目的：观察伊达比星加中剂量阿糖胞苷强化疗治疗急性髓系白血病（AML）的疗效和安全性。方法以北京军区总医院血液科2010年1月至2015年1月应用中剂量阿糖胞苷（2 g／m2,1次／12 h,第1天至第3天）联合伊达比星（12 mg／m2第1天）强化巩固治疗的50例诱导化疗缓解的 AML 患者为试验组,选择同期单药阿糖胞苷（2 g／m2,1次／12 h,第1天至第3天）治疗的50例患者为对照组。两组患者均序贯治疗6个疗程,试验组男性28例,女性22例,平均年龄27.6岁（18～52岁）,原发病包括M1型3例,M2型27例,M4型8例,M5型12例;对照组男性30例,女性20例,平均年龄26.8岁（16～50岁）,原发病包括 M1型2例,M2型30例,M4型8例,M5型10例。观察两组患者化疗并发症和无病生存等情况。结果随访至2015年6月,试验组1例死于肺部感染,2例死于感染性休克;对照组3例死于肺部感染,1例死于感染性休克。试验组和对照组患者治疗相关死亡率分别为6%（3／50）、8%（4／50）（P＞0.05）,复发率分别为32%（16／50）、52%（26／50）（P＜0.05）,无病生存率分别为62%（31／50）、40%（20／50）（P＜0.05）。结论伊达比星加中剂量阿糖胞苷强化疗治疗 AML 与单药阿糖胞苷相比复发率降低,无病生存率显著提高,且治疗相关死亡未增加,值得临床进一步应用。     

联合去甲氧柔红霉素治疗急性白血病的临床研究

采用以４－去甲氧基柔红霉素（ＩＤＡ）为主组成的联合化疗方案，治疗３３例初发和复发的急性白血病，其中急性淋巴细胞白血病（ＡＬＬ）７例，急性非淋巴细胞白血病（ＡＮＬＬ）２６例。结果：总有效率７０％。初治２３例ＡＮＬＬ患者，完全缓解（ＣＲ）１６例，部分缓解（ＰＲ）２例，有效率为７９％。５例初治ＡＬＬ患者，４例ＣＲ，１例ＰＲ。而复发的２例ＡＬＬ和３例ＡＮＬＬ患者均未缓解。ＩＤＡ主要副作用表现为骨髓抑制及心脏毒性。认为以ＩＤＡ组成联合化疗方案治疗初发的急性白血病具有较好的疗效     

Combination chemotherapy with 5-Fluorouracil,oral Idarubicin,and cyclophosphamide (FIC) in metastatic breast cancer—an open Phase II study

Summary Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxydaunorubicin), have shown antitumor activity in 23%–31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m² p.o. on days 1, 2, 3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received >2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean=51 years). In 25 patients a performance status of 0–2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m² i.v. days 1 and 8, Idarubicin 15 mg/m² p.o. days 1,2 and 3, and cyclophosphamide 500 mg/m² i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3–16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I–II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.     

Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia

Fourteen patients with poor-risk acute myelogenous leukaemia (AML) and five patients with accelerated phase/blast crisis chronic myeloid leukaemia (CML) were treated with 3 days of oral idarubicin (25 mg/m2/day). No complete remissions or return to chronic phase CML were observed. A fall in the peripheral blast count was seen in all patients with the first cycle of treatment, and with subsequent cycles in CML patients, but all responses were transient, with eventual reemergence of peripheral blasts. In some patients, there was a clear cut improvement in symptoms such as bone and splenic pain. Five of the AML patients and all of the CML patients were treated as out-patients. In this group of patients oral idarubicin was found to be a useful drug for palliative treatment.     

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。     

In Vitro Evaluation of Cytochrome P450-mediated Drug Interactions between Cytarabine,Idarubicin, Itraconazole and Caspofungin

Purpose: Antifungal prophylaxis is an important component of induction therapy for patients with acute myeloid leukemia (AML). Azole antifungal agents are increasingly used in this context. In vitro assays were performed to assess whether cytochrome P450 (CYP450) enzymes were affected by combinations of cytarabine or idarubicin with itraconazole or caspofungin.

Methods: The high throughput microtiter assay was used to determine whether cytarabine, idarubicin and itraconazole or caspofungin were CYP450 isoenzyme substrates, inhibitors of CYP450 isoenzymes, and to determine potential CYP450 metabolism interactions between these agents.

Results: Idarubicin is a substrate for CYP450 2D6 and 2C9. Cytarabine is a substrate of CYP450 3A4. Idarubicin inhibits CYP450 2D6, and cytarabine, itraconazole, and caspofungin inhibit CYP450 3A4. Cytarabine metabolism was significantly decreased when combined with caspofungin or itraconazole.

Conclusions: The inhibition of cytarabine metabolism may have important clinical implications. These in vitro findings warrant investigation with in vivo pharmacokinetic studies.