地西他滨联合IAG/DAG治疗急性髓系白血病的临床疗效

目的 探讨地西他滨（DAC）联合IAG/DAG治疗急性髓系白血病（AML）的临床疗效与安全性。方法 选取2017年6月至2019年12月安徽医科大学第一附属医院血液科收治的23例初治或复发AML患者,采用DAC联合IAG/DAG诱导治疗,统计分析临床疗效及安全性。结果 23例患者均予以DAC联合IAG/DAG诱导化疗,其中完全缓解13例,部分缓解2例,总有效率为65.22%。23例患者均出现Ⅲ～Ⅳ级的粒细胞和血小板减少,1例患者因严重脑出血死亡。结论 DAC联合IAG/DAG治疗AML临床疗效较好,且不良反应可耐受,安全性高,值得临床推广应用。     

伊达比星(4-去甲氧基柔红霉素)的结构研究.~1H-NMR和~(13)C-NMR的分析

伊达比星为新一代蒽环类抗肿瘤药物 ,目前国内已试制成功。我们对该品进行了 1 H-NMR、1 H- 1 H COSY、重水交换、1 3C- NMR、DEPT90°、DEPT135°、HMBC、HMQC和 NOSEY的测试 ,最终确定其构型为 α型 ,并对所有的 1 H和 1 3 C信号进行了归属。     

Prolonged survival of baboon renal allografts using idarubicin‐conjugated anti‐CD4 monoclonal antibodies

Abstract Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti‐CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T‐cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15‐25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti‐CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48‐h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h pre‐operatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti‐CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti‐CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti‐CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.     

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: A phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group

 Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2×500 mg/m²/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m²/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30–74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML. Received: 12 September 1995 / Accepted: 24 November 1995     

Subcutaneous low dose arabinosyl-cytosine and oral idarubicin in high risk adult acute myelogenous leukemia

In order to further explore low dose chemotherapy for high risk acute myelogeneous leukemia (AML), low dose Ara-C and oral idarubicin (LAI) were given to 33 patients of 24–84 (median 66) years with AML after myelodysplastic syndrome (MDS) (12 patients), refractory AML (13 patients), and AML with contraindications to intensive chemotherapy (8 patients). Patients received 1 to 4 cycles of Ara-C 10 mg/m² q 12 h s.c. inject. on days 1–14 and idarubicin 20 mg/m²/d orally days 3, 4, 5. Three patients attained complete remission, four patients partial remission and one patient minor response, whereas 11 patients succumbed to early mortality from hemorrhage (two patients) and/or infections (10 patients). Three of 13 patients with heavily pretreated refractory AML went into remission compared to 3/12 with AML after MDS and 1/8 with AML and contraindications against intensive treatment. Median duration of CR is 102 (70–488+) days. Thirty-two of 33 patients developed grade 4 hematological toxicity requiring platelet transfusions. The non-hematologic toxicity was acceptable. LAI provides a standardized therapeutic option especially for heavily pretreated patients with AML.     

Enhanced cellular delivery of idarubicin by surface modification of propyl starch nanoparticles employing pteroic acid conjugated polyvinyl alcohol

Enhanced intracellular internalization of the anti-cancer active idarubicin (IDA) was achieved through appropriate surface modification of IDA loaded propyl starch nanoparticles. This was conducted by synthesizing pteroic acid modified polyvinyl alcohol (ptPVA) and employing this stabilizer for formulating the said nanoparticles. Pteroic acid attached at the nanoparticles improved the surface protein adsorption of the nanoparticle, a condition which the nanoparticles would largely experience in vitro and in vivo and hence improve their cellular internalization.Spherical, homogenous IDA nanoparticles (214 ± 5 nm) with surface modified by ptPVA were formulated using the solvent emulsification-diffusion technique. The encapsulation efficiency and drug loading amounted around 85%. In vitro release studies indicated a controlled release of IDA. Safety and efficacy of the nanoparticles was confirmed by suitable cellular cytotoxicity assays. Protein binding studies indicated a higher adsorption of the model protein on nanoparticles formulated with ptPVA as compared to PVA. Cellular uptake studies by confocal laser scanning microscopy revealed a higher cellular uptake of ptPVA stabilized nanoparticles thus confirming the proposed hypothesis of higher protein adsorption being responsible for higher cellular internalization.     

IAG方案诱导治疗急性髓系白血病的临床效果观察

目的 探讨小剂量阿糖胞苷和去甲氧柔红霉素联合粒细胞集落刺激因子（G-CSF）组成的IAG预激方案治疗急性髓系白血病（AML）的疗效和患者不良反应.方法 回顾性分析25例AML患者在采用IAG预激方案诱导治疗1个疗程后的临床效果.IAG方案：去甲氧柔红霉素5 mg,静脉滴注,隔天1次,共7～8次;阿糖胞苷每12 h 10 mg/m2,皮下注射,第1天至第14天;G-CSF每天200 μg/m2,皮下注射,用药前一天至第14天.结果 化疗后总有效率80.0％（20/25）,完全缓解（CR）率60.0％（15/25）.初诊17例患者中,9例CR,4例部分缓解（PR）;复发难治患者8例中,6例CR,1例PR.骨髓增生异常综合征（MDS）转化的AML7例中,5例CR,2例PR;≥50岁的11例患者中,8例CR,1例PR.化疗的不良反应主要为骨髓抑制、胃肠道反应、肝肾功能损害;无早期死亡病例.结论 IAG预激方案是治疗AML（包括高危AML）的较有效、安全的方案.     

Mylotarg,fludarabine, cytarabine (ara-C), and cyclosporine (MFAC) regimen as post-remission therapy in acute myelogenous leukemia

Purpose Mylotarg, a humanized anti-CD33 antibody linked to an antitumor antibiotic, is approved for the treatment of patients with relapsed acute myeloid leukemia (AML). Its role as a component of post-remission therapy in AML has not been established. The Mylotarg, fludarabine, cytarabine, and cyclosporine (MFAC) regimen was evaluated in patients in complete remission following Mylotarg-containing regimens.Methods The MFAC regimen comprised: Mylotarg 4.5 mg/m² intravenously (i.v.) over 2 h after a loading dose of cyclosporine A (CSA) on day 1; fludarabine 15 mg/m² i.v. over 30 min every 12 h for six doses on days 2 through 4; ara-C 0.5 g/m² over 2 h every 12 h for six doses on days 2 through 4, 4 h after fludarabine started; CSA 6 mg/kg over 2 h, followed by 16 mg/kg continuous i.v. infusion on days 1 and 2. Patients in complete remission (CR) commenced idarubicin and ara-C (IA) alternating with MFAC or vice versa for 9 months from the date of CR. Idarubicin was administered at 8 mg/m² on days 1 and 2 and ara-C at 1.5 g/m² on days 1 and 2.Results A total of 22 patients received 76 courses of MFAC (35 courses) alternating with IA (41 courses) or vice versa. The interval between courses, and degrees of myelosuppression, were equivalent in the alternating regimens. Failure-free and 12-month survival rates of were 32% and 55%, respectively. Grade 3/4 toxicities, including sepsis, neutropenic fever, and nausea/vomiting, were equivalent with MFAC and IA.Conclusions Post-remission therapy with MFAC is feasible and well tolerated in patients with AML.     

Plasma Pharmacokinetics of Idarubicin and its 13-Hydroxymetabolite after Intravenous and Oral Administration under Fasting and Non-Fasting Conditions

The plasma pharmacokinetics of Idarubicin and its 13-hydroxymetabolite have been studied in 10 patients with solid tumours after intravenous and oral administration under fasting and non-fasting conditions in a randomized cross-over design. The plasma concentration time curves of Idarubicin after intravenous administration could be described by the open two or three compartment models. No pharmacokinetic modelling of Idarubicin was possible after oral administration. After oral administration of Idarubicin, the amount of intact drug was higher under non-fasting conditions. The extensive and long-lasting appearance of Idarubicinol suggests that this cytotoxic metabolite is of major clinical importance in i.v. and oral therapy with Idarubicin. The pharmacokinetics of Idarubicinol was not affected by food intake.     

高效液相色谱法测定盐酸伊达比星

用高效液相色谱法测定盐酸伊达比星（Ｉｄａｒｕｂｉｃｉｎｈｙｄｒｏｃｈｌｏｒｉｄｅ），ＯＤＳ柱，流动相为０．０１ｍｏｌ／Ｌ十二烷基硫酸钠溶液：异丙醇（５５：４５），ｐＨ３．０，检测波长２５４ｎｍ，以β－萘磺酸作内标，盐酸伊达比星含量在０．００５～０．５００ｍｇ／ｍｌ内峰面积与浓度线性关系良好，注射剂的平均回收率为９９．８％，重复进样相对标准差为０．４％，ｎ＝１０，方法简便，准确。