急性白血病中MDR1 MRP和bcl-2基因表达及其临床意义

目的:研究多药耐药基因(MDR1)、多药耐药相关蛋白基因(MRP)和调控细胞凋亡有重要作用的基因(bcl-2)在急性白血病(AL)中的表达以及它们与临床耐药之间的关系.方法:采用地高辛掺入的半定量逆转录聚合酶链反应(RT-PCR)及常规RT-PCR方法检测了54例急性白血病患者和10例正常人骨髓单核细胞中基因的表达情况.结果:54例AL中MDR1/MRP/bcl-2三基因表达阳性率为16.7%(9/54),MDR1/MRP/bcl-2三基因表达均阴性,发生频率为46.3%(25/54).46例资料完整的白血病患者中三基因表达均阴性者80.0%缓解(CR),MDR1/MRP或MDR1/MRP/bcl-2共表达者无1人CR(P＜0.01).单基因分析表明MDR1、MRP、bcl-2基因表达阳性率分别为28.3%、41.3%和47.8%,其中MDR1阳性者CR率7.7%,明显低于MDR1阴性者CR率72.7%(P＜0.01);MRP阳性CR率21.1%,明显低于阴性CR率77.8%(P＜0.01);bcl-2阳性CR率36.4%,亦低于阴性CR率70.8%(P＜0.05).结论:MDR1/MRP或MDR1/MRP/bcl-2共表达的患者不易获得CR,白血病患者的耐药除了与MDR1高表达密切相关外,还与非P-糖蛋白(P-gp)介导的MRP及bcl-2表达等因素相关.     

急性白血病中MDR1 MRP和bc1-2基因表达及其临床意义

目的:研究多药耐药基因(MDR1)、多药耐药相关蛋白基因(MRP)和调控细胞凋亡有重要作用的基因(bcl-2)在急性白血病(AL)中的表达以及它们与临床耐药之间的关系。方法:采用地高辛掺入的半定量逆转录聚合酶链反应(RT-PCR)及常规RT-PCR方法检测了54例急性白血病患者和10例正常人骨髓单核细胞中基因的表达情况。结果:54例AL中MDR1/MRP/bcl-2三基因表达阳性率为16.7%(9/54),MDR1/MRP/bcl-2三基因表达均阴性,发生频率为46.3%(25/54)。46例资料完整的白血病患者中三基因表达均阴性者80.0%缓解(CR),MDR1/MRP或MDR1/MRP/bcl-2共表达者无1人CR(P<0.01)。单基因分析表明MDR1、MRP、bcl-2基因表达阳性率分别为28.3%、41.3%和47.8%,其中MDR1阳性者CR率7.7%,明显低于MDR1阴性者CR率72.7%(P<0.01);MRP阳性CR率21.1%,明显低于阴性CR率77.8%(P<0.01);bcl-2阳性CR率36.4%,亦低于阴性CR率70.8%(P<0.05)。结论:MDR1/MRP或MDR1/MRP/bcl-2共表达的患者不易获得CR,白血病患者的耐药除了与MDR1高表达密切相关外,还与非P-糖蛋白(P-gp)介导的MRP及bcl-2表达等因素相关。     

非霍奇金淋巴瘤多药耐药的实验研究

目的 探讨初发非霍奇金淋巴瘤(NHL)mdrl mRNA及多药耐药蛋白P糖蛋白(P-gp)、肺耐药蛋白(LRP)和多药耐药相关蛋白(MRP)的表达频率及临床意义.方法 采用逆转录多聚酶链反应(RT-PCR)半定量方法检测41例初治NHL患者淋巴结活组织中瘤细胞mdrl mRNA的表达,采用流式细胞仪免疫荧光法检测P-gP、LRP、MRP的表达,以13例反应性增生淋巴结患者作为对照组.并分析多药耐药蛋白表达与NHL临床特征的关系.结果 41例NHL患者中,11例mdrl mRNA表达阳性,8例P-gP表达阳性,7例MRP表达阳性,15例LRP表达阳性.NHL组与对照组比较,MRP阳性率差异无统计学意义(P=0.887),LRP阳性率明显增高(P=0.047).NHL患者淋巴结组织P-gP、MRP、LRP表达两两之间均不存在相关关系,P-gP表达与mdrl mRNA表达正相关(r=0.396,P=0.01).P-gP表达与临床分期、LDH水平有关(均P<0.05),而与恶性分级无关.MRP表达与临床分期、恶性分级、血清乳酸脱氢酶(LDH)水平均无关(均P>0.05),而LRP表达与三者均有关(均P<0.05).P-gP和LRP表达阳性患者的完全缓解(CR)率分别为37.5%和53.3%,低于阴性表达者(均P<0.05),化疗疗效较差,而MRP表达与化疗疗效无关.结论 P-gP、LRP可能是NHL原发耐药的主要因素,影响NHL患者的化疗疗效,而MBP与NHL原发耐药无关,不影响NHL患者的化疗疗效.     

急性白血病mdr-1、bcl-2的表达及其临床意义

目的探讨mdr-1基因与bcl-2基因表达对急性白血病患者疗效判断的临床意义。方法应用逆转录-聚合酶链反应(RT-PCR)法检测51例急性白血病患者mdr-1基因及bcl-2基因的表达,结合临床分析,观察mdr-1基因及bcl-2基因的表达与临床化疗疗效的关系。结果51例急性白血病患者中mdr-1基因表达阳性21例(41.2%),bcl-2基因表达阳性28例(54.9%)。相关分析表明,mdr-1阳性表达与bcl-2阳性表达无相关关系(Pearsonγ=0.15,P>0.05)。mdr-1基因表达阴性者治疗完全缓解(CR)率达70.0%,明显高于表达阳性者CR率(19.0%)(P<0.05);bcl-2基因表达阴性者CR率为78.3%,明显高于表达阳性者的25%(P<0.05)。两者表达均为阳性者14例中CR1例,CR率为7.1%,表达均为阴性者16例中CR15例,CR率为93.8%,两者比较有极显著差异(P<0.01)。结论检测mdr-1基因或bcl-2基因对判断急性白血病的疗效有良好的预测作用,联合检测意义更大,可作为临床判断疗效的一项有意义的指标。     

非M3型急性白血病患者中MUC1基因和MDR1基因表达及其与临床疗效的关系

背景与目的:MUC1基因在胃癌、卵巢癌、多发性骨髓瘤、恶性淋巴瘤等肿瘤中有表达,在急性白血病患者中有较高的表达。但MUC1基因和多药耐药基因(MDR1)相互关系以及两者的表达与急性白血病治疗效果的关系尚有待探讨。本研究拟探讨MUC1基因与MDR1基因表达及其与非M3型急性白血病患者治疗效果的关系。方法:应用逆转录鄄聚合酶链反应(RT鄄PCR)法检测34例初治非M3型急性白血病患者MUC1和MDR1的表达,并观察两种基因表达及其与临床疗效的关系。结果:34例初治非M3型急性白血病患者中MUC1基因阳性率为50%,MDR1基因阳性率为29.4%。MUC1基因阳性患者的MDR1阳性率为52.9%,明显高于MUC1阴性者的5.9%(P=0.003)。MUC1基因阴性者完全缓解(CR)率达94.1%,阳性患者CR率52.9%,两组有显著性差异(P<0.05);MDR1基因阴性者CR率为91.7%,明显高于阳性患者的50.0%(P<0.05)。MUC1基因和MDR1基因均阳性者CR率为55.6%,MUC1基因和MDR1基因均阴性者16例,全部获得CR。结论:非M3型急性白血病MUC1基因阳性者MDR1基因表达率较高,MUC1基因及MDR1基因均为阴性者治疗缓解率高。提示联合检测MUC1基因和MDR1基因对判断初治非M3型急性白血病的疗效有良好的预测作用,可作为临床判断疗效的一项有意义的指标。     

SSX2基因在急性白血病中表达的临床意义

目的:研究滑膜肉瘤X断裂点基因2(SSX2)在急性白血病中的表达及临床意义.方法:逆转录聚合酶链反应检测72例急性白血病(AL)中SSX2的表达,包括23例急性淋巴细胞白血病(ALL)及急性髓细胞白血病(AML).结果:在72例AL患者中有38例SSX2表达阳性(52.78%),在ALL中SSX2表达阳性率为56.52%,而在AML中SSX2表达阳性率为51.02%,两者之间没有显著性差别(P<0.05).在非M3型AML患者中SSX2表达阳性的完全缓解率(CR)为60.87%,而在SSX2表达阴性的完全缓解率为89.47%.在随访的16例SSX2表达阳性患者观察治疗后的SSX2表达阳性率,完全缓解后SSX2表达可以转为阴性,SSX2表达持续阳性的患者会较早复发.如果患者没有完全缓解,则SSX2表达不会转为阴性.结论:在AML及ALL患者中SSX2表达没有差别(P>0.05),SSX2阳性表达非M3型AML患者中CR率较低,SSX2可以作为AML患者较差的预后指标.     

初治急性白血病患者p170和MRP蛋白表达与预后的关系

目的：探讨多药耐药蛋白(p170)和多药耐药相关蛋白(MRP)表达与初治急性白血病(AL)患者化疗效果的关系。方法：用流式细胞仪检测29例初治AL患者骨髓单个核细胞中p170和MRP蛋白表达。结果：初治AL患者p170和MRP蛋白表达率分别为37.9％和41.4％；MRP蛋白阳性与阴性患者的首次完全缓解(CR)差异无显著性(P＞0.05)；而p170蛋白阳性与阴性患者的首次完全缓解(CR)有显著性差异(P ＜0.05)；p170和MRP蛋白两者之间无相关性。结论：作为预测初治AL患者化疗效果的敏感性指标，p170明显优于MRP蛋白。     

急性白血病耐药蛋白表达与临床疗效及预后的关系

目的:研究急性白血病(AL)耐药蛋白表达与临床疗效及预后的关系。方法:采用免疫组化法对40例初发AL耐药蛋白PGP、MRP1的表达进行检测,并分析其与病人预后的关系。结果:PGP表达阳性的AL中CR率36.36%,PGP表达阴性的AL中CR率92.85%(P<0.01);MRP1表达阳性的AL中CR率44.44%,MRP1表达阴性的AL中CR率为95.45%(P<0.01);PGP、MRP1同时表达阳性,CR率42.85%,全阴性的AL,CR率100%(P<0.01)。结论:PGP和MRP1的表达与白血病疗效及预后之间存在着一定的相关性。     

HOX11原癌基因的活化对儿童急性白血病预后的影响

目的:探讨HOX11原癌基因的活化对儿童急性白血病(acute leukemia,AL)预后的影响。方法:对HOX11原癌基因表达阳性和阴性的282例初治急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)及82例急性髓细胞白血病(acute mye-locytic leukemia,AML)患儿正规化疗后的治疗效应进行研究和分析。结果:在标危、中危、高危组ALL患儿的正规化疗中,HOX11原癌基因阳性表达患儿的复发或死亡率均明显高于表达阴性的患儿(分别为P<0.005,P<0.01,P<0.005);在AML患儿中,HOX11原癌基因阳性表达患儿的复发或死亡率虽与HOX11表达阴性患儿相比较差异无统计学意义P>0.05),但HOX11原癌基因活化的AML患儿临床化疗效果差。结论:HOX11原癌基因的活化可能影响AL的预后。     

鼻NK/T细胞淋巴瘤耐药基因相关蛋白的检测

目的:探讨鼻NK/T细胞淋巴瘤耐药基因相关蛋白的表达情况,为选择化疗方案提供帮助.方法:免疫组化染色选用的抗体有5种耐药基因相关蛋白,包括:P-糖蛋白(P-170),多药耐药相关蛋白(MRP),肺耐药相关蛋白(LRP),拓扑异构酶Ⅱ(TopoⅡ),谷胱甘肽-S-转移酶(GST～π).结果:68例NK/T细胞淋巴瘤的耐药基因相关蛋白表达P-170和MRP均为阴性;GST-π阳性33例(48.53%),其中强阳性16例(23.53%),阳性17例(25.00%);LRP阳性14例(20.59%),其中强阳性3例(4.41%),阳性11例(16.18%);TopoⅡ染色Ⅰ级24例(35.29%),Ⅱ级25例(36.76%),Ⅲ级12例(17.65%),Ⅳ级7例(10.29%).GST-π、LRP和TopoⅡ表达两两比较,其结果均无统计学差异.结论:P-170和MRP可能存在共同的调节因子,且与NK/T细胞淋巴瘤耐药无关.LRP、TopoⅡ和GST-π与NK/T细胞淋巴瘤化疗疗效密切相关.检测NK/T细胞淋巴瘤耐药基因相关蛋白的表达对临床化疗方案的选择提供帮助.     

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome.     

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     

Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas.

Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.     

Evaluation of 58 patients with acute leukemia]

We made a retrospective study of 44 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) admitted to our hospital from September 1984 to May 1991. The complete remission (CR) rate of ANLL was 90.9%, against 85.7% for ALL. The 5-year survival of ANLL was 50.7%, and that of ANLL under age 60 years was 70.3%. The 2-year median survival of ALL was 35.1%. These results were obtained with response-oriented individualized therapy, and intensive chemotherapy with a view to eradication of residual leukemic cells. Eight elderly patients with ANLL were treated with cytosine arabinoside in low doses. Complete remission was achieved in 6 patients, but these cases relapsed. These treatments should be reconsidered for long CR duration. Our schedules of response-oriented individualized therapy were too flexible to apply at another institute so they should be arranged for general application.     

Clinical trials with daunorubincin-DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood,acute nonlymphoblastic leukemia,and bronchogenic carcinoma

Summary Treatment with daunorubicin-DNA (DNR-DNA) or adriamycin-DNA (ADM-DNA) has been evaluated in acute lymphoblastic leukemia of childhood (ALL), acute nonlymphoblastic leukemia (ANLL) and bronchogenic carcinoma (BC). The Five-year survival rate in 69 children with ALL was 73.7% when ADM-DNA was introduced in the treatment and 38% with DNR-DNA (P=0.03).A randomization between free DNR and DNR-DNA for remission induction in 26 patients with ANLL has shown that the drugs were of equivalent effectiveness. The one-year survival rate was 66% for the DNR group and 64% for the DNR-DNA group.In 59 patients with BC, a randomized trial between ADM-DNA and cyclophosphamide-vinblastine (CTX-VLB) did not show an advantage infavor of one of these treatments. In anaplastic BC (51 patients), there was no difference in survival rate or remission rate between patients treated with ADM or ADM-DNA.No cardiotoxicity was noted among the patients treated with the complexed drugs. ADM-DNA and DNR-DNA are as effective as the free drugs. Cardiotoxicity appears to be reduced.Aspirant du Fonds National de la Recherche Scientifique de Belgique     

老年人急性髓细胞白血病多药耐药蛋白过度表达的实验与临床研究

 目的　初步分析老年急性髓细胞白血病（AML）患者P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）、肺耐药蛋白（LRP）的表达及其在预后中的意义。方法　流式细胞仪活细胞直接或间接免疫荧光法检测12例初治老年AML（M2a 4例,其中1例由MDS转化而来;M4a 2例;M5a 5例;M6 1例）患者骨髓白血病细胞P-gp、MRP、LRP表达情况。分析这些多药耐药蛋白表达与预后的关系。结果　P-gp、MRP、LRP的表达率分别为58.33 %、8.33 %、50 %;P-gp(+)、MRP(+)0,P-gp(+)、LRP(+)33.33 %,MRP(+)、LRP(+)0,P-gp(+)、MRP(+)、LRP(+)8.33 %,P-gp(-)、MRP(-)、LRP(-)33.33 %,其中P-gp、LRP单独和二者共表达频率较高。P-gp(+)者的完全缓解（CR）率与2年总生存率（OS）均显著低于P-gp(-)者（P＝0.01）,LRP(+)者的CR率与2年OS亦均低于LRP(-)者。结论　老年AML患者 P-gp、LRP单独及二者共表达频率均较高。P-gp、LRP过度表达是老年AML患者的不良预后因素。     

EB病毒在儿童白血病患者中的感染状况及其临床意义——附35例报告

背景与目的:Epstein-Barr病毒(EBV)与多种肿瘤的发生密切相关,为此我们探讨在儿童白血病中EBV的感染及其临床意义.方法:采用荧光定量聚合酶链反应(fluorescence quantitative-polymerase chin reaction,FQ-PCR)技术,检测35例儿童白血病[其中急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)26例(初治24例,复治2例);急性非淋巴细胞性白血病(acute nonlymphocytic leukemia,ANLL)8例;慢性淋巴细胞性白血病(chronic lymphocytic leukemia,CLL)1例]及14例正常儿童外周血单核细胞EBV-DNA的含量,并结合患儿的临床表现、泼尼松敏感试验、诱导治疗完全缓解率,分析在儿童白血病患者血中EBV的感染及其临床意义.结果:35例儿童白血病患儿中8例(22.86%)有EBV感染.其中26例ALL中7例(26.92%)EBV感染,EBV-DNA含量为(5.14±6.91)×105 copy/ml;8例ANLL中1例(12.5%)EBV感染,EBV-DNA含量为4.031×103 copy/ml;1例CLL及14例正常对照儿童未检测到EBV-DNA的含量.EBV感染的儿童白血病患儿白细胞数[(144.64±46.41)×109 /L]和肝脾肋下≥5 cm发生率87.5%均高于非EBV感染患儿[(31.04±60.27)×109 /L和7.4%,P＜0.001].感染EBV和非EBV感染的ALL患儿泼尼松疗效者分别为100%、26.32%(P=0.001);诱导治疗完全缓解率分别为28.57%、84.21%(P=0.003).ANLL患儿中,1例感染EBV者的诱导治疗完全缓解率(100%)和早期复发率(100%)较未感染EBV的7例(84.21%,28.57%)高,二者无显著性差异(P＞0.05).结论:EBV感染组儿童白血病患儿肝脾肿大明显,外周血白细胞数明显高于非EBV感染者,EBV感染ALL组对泼尼松敏感试验反应差,诱导治疗获得完全缓解率低.     

Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia.

In vitro resistance to anthracyclines is related to a poor prognosis in childhood acute lymphoblastic leukemia (ALL), but the underlying mechanisms are poorly understood. Using flow cytometry, we studied the contribution of daunorubicin (DNR) accumulation and retention, cell size, expression of the major vault protein/lung resistance protein (LRP), P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) to the cytotoxicity of DNR (by MTT assay) in childhood ALL. The accumulated and retained DNR content was not related to the degree of DNR resistance, nor did the content differ between 53 initial and 20 relapse ALL samples (P >0. 05), although the latter were median two-fold more resistant to DNR (P = 0.004). Leukemic cell volume correlated with resistance to the anthracyclines DNR (Rs 0.32, P = 0.012) and idarubicin (Rs 0.46, P = 0.011) but not to other classes of drugs such as prednisolone, vincristine, L-asparaginase and etoposide. Relapsed patients had 1. 5-fold larger cells than patients at initial diagnosis of ALL (P = 0. 001). After cell volume correction, the intracellular DNR concentration was lower in relapsed compared with initial ALL cells (eg 60 min accumulation, P = 0.003). Moreover, the intracellular DNR concentration inversely correlated with DNR resistance, both in the accumulation (Rs -0.44, P < 0.001) and retention (Rs -0.33, P = 0. 016) test condition. The accumulated DNR concentration inversely correlated with expression of LRP (Rs -0.36, P = 0.012) but not with P-gp and MRP. Expression of LRP, but not of P-gp and MRP, significantly correlated with DNR resistance in childhood ALL (Rs 0. 33, P = 0.03). In conclusion, the intracellular DNR concentration and the expression level of LRP may contribute to DNR resistance in childhood ALL. The strength of the correlations also indicates that resistance to anthracyclines can not be explained by one single mechanism.     

Mitoxantrone for refractory and relapsed acute leukemia

Seventy-seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily X 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first-line therapy in ANLL.     

改良FLAG方案治疗33例难治复发性急性白血病的初步分析

背景与目的:FLAG方案用于治疗难治复发性急性非淋巴细胞性白血病(acute non-lymphocytic leukemia,ANLL)已有多年,大多报道的CR率为50%～64%.本研究探讨改良FLAG方案(减少合并应用Ara-C剂量并在化疗前不用G-CSF)能否达到同样疗效,并减轻不良反应.方法:33例成人急性白血病中难治性ANLL 16例,难治性急性淋巴细胞白血病(ALL)12例,复发性ALL 5例.全部病例接受氟达拉宾30 mg@(m2@d)-1,静滴,第1～5天;其中合并Ara-C 200 mg@d-1有18例,Ara-C 500 mg@d-1有5例,Ara-C 1 000 mg@d-1有10例,全部静脉滴注5～7天为1疗程.应用Ara-C 200 mg@d-1组和ALL组化疗前不用G-CSF,ALL患者每周加用长春新碱2 mg,共2次;强的松60～80 mg@d-1,共14天.化疗后WBC＜1.0×10 9/L者加用G-CSF,剂量均为300μg@d-1,皮下注射至WBC 3.0×10 9/L以上.每疗程完成后复查骨髓.结果:16例难治性ANLL的CR率为56.3%,而12例难治性ALL的CR率为8.3%(P＜0.01);难治性ANLL患者中Ara-C 200 mg@d-1组的CR率高于500～1 000 mg@d-1组(70%:33%),但无统计学差异(P＞0.05).化疗后WBC 0.6×10 9/L和血小板15.6×10 9/L的平均持续时间分别为5天和4.3天,Ara-C 200 mg@d-1组感染发生率明显低于500～1 000 mg@d-1Ara-C组(58.0%:85.7%)(P＜0.05).结论:与经典的FLAG方案相比,改良FLAG方案的CR率有增高、感染发生率降低.