DCAP方案治疗成人难治性急性淋巴细胞白血病临床观察

难治性白血病经标准化疗两个疗程后未能缓解通常选择与原用药物无交叉耐药的药物组成新的治疗方案，1995年2月～2002年12月，我们采用DCAP方案治疗26例成人难治性急性淋巴细胞白血病(ALL)，现报告如下。     

小儿急性淋巴细胞白血病的药物治疗

小儿白血病可分为急性淋巴细胞白血病(ALL)和急性非淋巴细胞白血病(ANLL)2大类,其中ANLL的治疗尚未取得突破性进展.白血病患儿绝大多数是ALL,治疗的疗效很好,应用有效的化学治疗方案,其5年存活率可达70%以上[1].现对小儿ALL的药物治疗作一简要介绍,供参考.     

MEA治疗难治性白血病及其核基质的变化研究

探索了用米托蒽醌、VP-16、阿糖胞苷联合化疗治疗难治性急性淋巴细胞白血病及其前后细胞核基质蛋白的变化.结果三药联用的有效率为66.7%,明显高于对照组.说明米托蒽醌、VP-16、阿糖胞苷联合化疗对治疗难治性急性淋巴细胞白血病有效,核基质是某些抗癌药物的作用点,分子量为180KD的核基质蛋白缺失可能与细胞耐药性有关.     

急性白血病体外药敏试验的临床应用

急性白血病体外药敏试验的临床应用何争春，周挚，梁瑞琼关键词急性白血病，化疗药物，药敏试验化疗迄今仍是治疗白血病的主要手段，如何能在体外短期内选择敏感的药物，从而组成对白血病细胞有最大杀伤力的治疗方案，一直是临床迫切需要解决的问题。笔者于１９９１年１０...     

蒽环类抗生素在抗白血病中的地位与现状

自Skipper的细胞增殖动力学的发现．使恶性肿瘤和白血病的治疗取得了革命性的突破。新药的不断发现，新方案的组成使恶性肿瘤的治疗展现了鼓舞人心的前景。以急性非淋巴细胞性白血病(ANLL)为例．60年代我国ANLL患的中数生存期是11～15d，而现今40%～70%的ANLL患可获完全缓解(CR)，其中20%～30%的患通过化疗可望长期生存。尤其是儿童非高危急性淋巴细胞性白血病(ALL)患，     

去甲氧柔红霉素联合化疗方案治疗初治儿童急性非淋巴细胞白血病

目的 探讨4-去甲氧柔红霉素(IDA)对初治儿童急性非淋巴细胞白血病(ANLL)的治疗效果和毒、副作用。方法 对使用IDA联合Ara-C方寨诱导化疗的儿童ANLL 25例进行临床分析。结果 25例患儿CR17例：PR3例、NR3例;2例早期死亡,总CR章78．9％．第一疗程CR率65.21％,总有效率86．95％。随防23例中16例(69．57％)持续缓解。儿童使用IDA的主要毒、副作用是骨髓抑制、出血、感染、口腔粘膜炎,心脏、肝毒性较轻。结论 IDA联合化疗方案治疗初治儿童急性非淋巴细胞白血病的疗效较好。     

MA方案治疗成人急性非淋巴细胞白血病的疗效分析

目的 评价米托蒽醌、阿糖胞苷(MA)方案作诱导治疗成人急性非淋巴细胞白血病(ANLL)初治患者的疗效.方法 采用米托嗯醌(mitoxantrone)和阿糖胞苷(cytarabine)对35例成人ANLL患者进行联合化疗.结果 临床和血液学完全缓解(CR)15例(42.9%),部分缓解(PR)9例(25.7%),总有效率68.6%.结论 在强力支持治疗的基础上,MA方案治疗成人难治性急性非淋巴细胞白血病有较好的疗效,其毒副作用可以耐受.     

去甲氧柔红霉素治疗难治和复发小儿急性白血病疗效探讨(附11例报告)

去甲氧柔红霉素(ID)是一种新的蒽环类药物,我们自1995年2月至1998年12月采用以ID为主化疗方案治疗11例难治和复发小儿急性白血病取得一定疗效,现报告如下。1　一般资料本组11例均为住院患儿,男7例,女4例;年龄3～12岁。急性淋巴细胞白血病(ALL)7例,其中难治性2例,复发5例,有2例第二次复发。急性非淋巴细胞白血病(ANLL)4例,其中难治性2例,复发2例。11例均接受两个疗程以上治疗。难治性ALL曾接受DOCP或VDLP方案4周未取得缓解。难治性ANLL曾接受标准剂量DA或EA方案两个疗程。复发病例系完全缓解后而在重新诱导治疗中使用过标准剂量…     

IEA方案治疗难治性急性淋巴细胞白血病疗效观察

目的观察IEA方案治疗难治性急性淋巴细胞白血病的疗效和不良反应。方法 15例难治性急性淋巴细胞白血病患者均给予IEA方案(IDA10mg/d,第1～3天,第15～17天;足叶乙苷(VP16)0.1g/d,第1-5天;阿糖胞苷Ara-C0.2g/d,第1～7天。结果 13例患者中,第1疗程获CR8例,CR率61.3%,PR1例,总有效率69.2%;NR4例。结论 IEA方案治疗难治性急性淋巴细胞白血病的疗效好,不良反应轻。     

老年急性白血病37例临床分析

[目的]分析老年急性白血病临床特点,化疗方案及预后疗效等.[方法]对2003年至2010年间初治老年急性白血病37例进行分析,中位年龄71岁(60 ～ 93岁),男16例,女21例.急性淋巴细胞白血病(ALL)5例;急性非淋巴细胞白血病(AML)32例,以M2 (40.6％)为主.26例患者接受联合化疗,治疗予NA、TA及NAOP 方案进行联合化疗.[结果]完全缓解率26.9％,2年存活率11.5％,死亡率81％.[结论]老年急性白血病总体缓解率低,死亡率高,化疗耐受性差.     

Activity of etoposide (VP-16) and teniposide (VM-26) in exponential and plateau phase human tumor cell cultures.

The effects of etoposide (VP-16) and teniposide (VM-26) have been evaluated in human epidermoid carcinoma cells (A431, ME180 and HEp3) grown as exponential and plateau phase cultures. A significant increase in resistance to both these chemotherapeutic agents was observed in unfed plateau compared with exponential phase cells. The large differences in cell killing could not be explained by cell cycle specific toxicities resulting from variations in the cell cycle distributions. Rather the differences in the treatment efficacies probably reflect the 5- to 15-fold increase in the proportion of quiescent cells measured in the plateau phase cultures. These findings suggest that non-proliferating cells in tumors may be preferentially spared in treatments utilizing VP-16 and VM-26.     

Novobiocin-induced VP-16 accumulation and MRP expression in human leukemia and ovarian carcinoma cells

We have previously reported that novobiocin potentiates the cytotoxic activity of etoposide (VP-16) and teniposide (VM-26) in a number of experimental tumor cell lines by inhibition of the efflux of the epipodophyllotoxins by an ATP-requiring transporter. In leukemia cells from 12/19 patients and in ovarian carcinoma cells from 2/4 patients, novobiocin, in a concentration range of 150-1000 microM, increased the intracellular accumulation of VP-16 by 30-250% by inhibiting its efflux. Novobiocin did not significantly increase the intracellular concentration of VP-16 in human mononuclear bone marrow cells from two individuals with normal bone marrow, suggesting that it might be possible to selectively modulate the intracellular accumulation of the epipodophyllotoxin in tumor cells relative to normal hematopoietic tissue. Previous findings from our laboratory have provided evidence that the membrane transporter for VP-16 which is inhibited by novobiocin is distinct from the P-glycoprotein. The expression of MRP, measured by immunoblotting, was variable in novobiocin-responsive and non-responsive leukemia cells, indicating that no direct relationship existed between the modulatory activity of novobiocin on the transport of VP-16 and the expression of the MRP gene. The findings indicate that the novobiocin-sensitive VP-16 transporter is (i) present in high frequency in leukemia and ovarian carcinoma cells, and (ii) probably not the P-glycoprotein or MRP.     

白血病患者P27(Kip1)表达的初步研究

目的：研究白血病患P27（Kipl)的表达及其与白血病预后的关系。方法：用蛋白印迹法（Western blot)加化学发光法研究23例急性白血病患骨髓或外周血中白血病细胞的P27（Kipl)蛋白表达。结果：P27（Kipl)总阳性率为78．26％（18／23），但表达强度不一。急性非淋巴细胞白血病（ANLL）阳性率82．35％（14／17），4例急性淋巴细胞白血病（ALL）中2例阳性一，1例慢性粒细胞白血病急变期（CML－BC）为阳性，1例淋巴肉瘤白血病为阳性。P27（Kipl)低表达组与高表达组生存率无显差异。13例已死亡的ANLL中P27（Kipl)高表达组总生存期长于低表达组（秩和检验P＝0．05）。所有进行化疗的18例患达到完全缓解（CR）P27（Kipl)平均表达强度高于未完全缓解（NR），但无统计学意义（秩和检验P＞0．05）。诊断时外周血白细胞数、血乳酸脱氢酶水平与P27（Kipl)无相关性。结论：P27（Kipl)的表达与ANLL的预后可能相关，高P27（Kipl)预后好。     

Components of intrinsic drug resistance in the rat hepatoma.

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.     

替尼泊苷联合卡铂与依托泊苷联合卡铂一线治疗小细胞肺癌的长期随访研究

目的 长期随访比较替尼泊苷（Teniposide,VM-26）联合卡铂（Carboplatin,CBP）（TC方案）与依托泊苷（Etoposide,VP-16）联合卡铂（EC方案）一线治疗小细胞肺癌（Small cell lung cancer,SCLC）的疗效及对脑转移的预防作用。方法 102例初治、无脑转移的SCLC患者接受治疗,其中EC方案（VP-16组）64例,TC方案（VM-26组）38例,患者一般临床特征经χ2检验,两组具有可比性（P﹥0.05）。化疗后达PR或CR者给予预防性脑照射（prophylactic cranial irradiation, PCI）。结果 VM-26组CR 4例,PR 26例,SD 7例,PD 1例,ORR为78.9%,DCR为97.4%,中位PFS为10个月,中位OS为18个月;VP-16组CR 7例,PR 42例,SD 12例,PD 3例,ORR为76.6%,DCR 95.3%,中位PFS为9个月,中位OS为16个月。VM-26组1、2、3年OS分别为73.7%、36.8%和18.4%;VP-16组1、2、3年OS分别为71.9%、37.5%和18.8%。两组有效率、疾病控制率及生存期均无统计学差异（P﹥0.05）。VM-26组脑转移发生率为21.1%,VP-16组为43.8%,VP-16组明显高于VM-26组,有统计学差异（P=0.020）。不良反应主要是骨髓抑制,多为I、II度,两组比较无统计学差异（ P﹥0.05）。结论 TC方案治疗SCLC疗效肯定,其近期疗效和长期生存与EC方案相似,且该方案一定程度上可降低脑转移发生率,耐受性较好,可作为初治SCLC的一线治疗方案。     

Inhibitory effect of curcumin onMDR1 gene expression in patient leukemic cells

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1(MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of 10 microM curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.     

异搏定对化疗药物体外净化白血病细胞的增强效应

用体外克隆形成培养技术研究异搏定（ＶＰＬ）对化疗药物阿霉素（ＡＤＭ）、长春新碱（ＶＣＲ）及足叶乙甙（ＶＰ－１６）体外净化白血病细胞作用的影响，结果显示ＶＰＬ能明显提高不同浓度的３种药物体外对Ｋ５６２、Ｒａｊｉ及Ｌ－ＣＦＵ的杀伤敏感性，而不增加其对ＧＭ－ＣＦＵ的毒性。２．２０μｍｏｌ·Ｌ－１ＶＰＬ联用０．９２μｍｏｌ·Ｌ－１ＡＤＭ、０．０２５μｍｏｌ·Ｌ－１ＶＣＲ或１．７１μｍｏｌ·Ｌ－１ＶＰ－１６对Ｌ－ＣＦＵ的杀伤作用分别为不加ＶＰＬ组的１．９６、１．６５及１．９５倍，而ＧＭＣＦＵ集落存活率则无明显改变，提示ＶＰＬ能选择性提高上述化疗药物的体外净化白血病细胞效果。     

Phase I–II trial of mitoxantrone in acute leukemia: an interim report

Summary We evaluated the effect of mitoxantrone (Novantrone®; dihydroxyanthracenedione) in the treatment of refractory acute leukemia and acute leukemia in relapse. In this study, 70 patients are currently evaluable. Of the 25 patients who received mitoxantrone 10 mg/m² × 5, two of 10 with ANLL in relapse, one of five with ALL in relapse achieved complete remission, and one of seven with blastic phase CML responded. At a dose of 12 mg/m² × 5, nine of 22 patients with ANLL in relapse, one of five patients with blastic phase CML and none of the nine patients with ALL responded. At this dose all remissions occurred after one course of treatment. None of the patients with ANLL or ALL refractory to primary therapy achieved a remission. Toxicities encountered with both dose levels were comparable. However, second courses at 12 mg/m² × 5 led to severe stomatitis and prolonged cytopenia. We conclude that mitoxantrone is effective therapy for ANLL in relapse and that 12 mg/m² per day × 5 is the optimal dose schedule. A randomized trial comparing daunorubicin with mitoxantrone in combination with cytarabine in untreated patients with ANLL should answer whether mitoxantrone is less toxic and whether it should replace daunorubicin in standard induction therapy in ANLL.See Table 1