全反式维甲酸联合三氧化二砷及蒽环类药物治疗急性早幼粒细胞白血病44例

目的 探讨全反式维甲酸(ATRA)与三氧化二砷(As2O3)联合蒽环类药物(ATC)治疗初治急性早幼粒细胞白血病(APL)的疗效和不良反应.方法 44例初发APL患者均符合FAB分型诊断标准,其中25例行荧光原位免疫杂交(FISH)检查PML-RARα融合基因均为阳性.均以ATRA+As2O3双诱导,白细胞>15×109/L时,加用ATC,达完全缓解(CR)后,每月以ATC联合阿糖胞苷(Ara-C)化疗1个疗程,共3个疗程,继以ATC联合化疗、ATRA、As2O3序贯.观察其疗效和不良反应.结果 44例APL患者,早期死亡1例(诱导治疗1周死于弥漫性血管内凝血并颅内出血),43例达CR,CR率97.73%,获得CR的时间(27.3±5.2)d,43例目前均持续CR,25例初诊时PML-RAR α融合基因阳性者,巩固化疗结束时均转为阴性,治疗过程中无严重不良反应发生.结论 ATRA与As2O3联合ATC治疗APL效果满意,不良反应少.     

复方黄黛片治疗急性早幼粒细胞白血病的系统评价

目的 评价复方黄黛片( CRNTT)治疗急性早幼粒细胞白血病(APL)的疗效与安全性。方法计算机检索SinoMed、CNKI、VIP、万方、CBA、PubMed、MEDLINE、EMBASE、Cochrane图书馆临床对照试验资料库,并辅以手工检索,收集国内外公开发表的CRNIT治疗APL的随机对照试验(RCT)文献,检索年限截至201 1年3月。按纳入标准与排除标准筛选文献并评价纳入研究的质量,以完全缓解(CR)率、达CR所需时间、复发率、病死率、不良反应率等为评价指标,采用RevMan 5.1软件进行Meta分析。结果纳入6项RCT,包括391例APL患者,其中2项RCT研究目的为CRNIT与三氧化二砷(ATO)的比较,4项RCT研究目的为CRNIT与全反式维甲酸(ATRA)的比较,其中1项RCT增设CRNIT+ ATRA与ATRA的比较。达CR所需时间：CRNIT比ATRA、ATO长[加权均数差(WMD)=3.14,95％CI 0.99 ～5.29,P=0.004];头痛发生率：CRNTT低于ATRA（OR=0.10,95％CI 0.02～0.45,P=0.003）;5年无病生存率：CRNIT优于ATRA（OR= 7.22,95％CI 1.40～37.25,P=0.02）;CR率、复发率、病死率和4项不良反应指标（胃肠道症状、肝肾功能损害、皮肤损害、发热）的Meta分析结果差异无统计学意义。结论服用CRNIT达CR所需时间比ATRA、ATO长,CRNIT近期疗效与ATRA、ATO相近。服用CRNIT的5年无病生存率可能优于ATRA。     

全反式维甲酸、三氧化二砷、化疗联合治疗急性早幼粒细胞白血病疗效观察

目的 评估全反式维甲酸(ATRA)、三氧化二砷(As2O3)、化疗联合治疗初诊急性早幼粒细胞白血病(APL)的疗效和患者不良反应.方法 对40例采用ATRA、As2O3、化疗三联疗法治疗的APL患者的临床资料进行回顾性分析,观察其疗效及不良反应.结果 总体CR率92.5%(37/40),完全缓解所需中位时间27(22～61)d;白细胞≥10×109/L组CR率72.7%(8/11),白细胞<10×109/L组CR率100%(29/29),差异有统计学意义(x2=8.550,P=0.004);治疗过程中无严重不良反应,仅1例发生维甲酸综合征.结论 ATRA、As2O3、化疗联合应用可作为APL患者的首选治疗方案.     

三氧化二砷联合全反式维甲酸治疗初发急性早幼粒细胞白血病的临床观察

目的 观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗初诊急性早幼粒细胞白血病(APL)的疗效及不良反应.方法 对ATRA每天25mg/m2联合As2O310mg/d(联合组)治疗的35例APL患者达完全缓解(CR)时间、CR率、早期病死率及不良反应进行观察,并与单用As2O3 10 mg/d(单药组)治疗的33例进行比较.结果 联合组CR率为94.3%(33/35),与单药组[90.9%(30/33)]比较差异无统计学意义(P>0.05);联合组获得CR时间为26.1 d,短于单药组的30.5 d,差异有统计学意义(P<0.05);联合组与单药组APL分化综合征及不良反应发生率、早期病死率比较,差异均无统计学意义(均P>0.05);高WBC组比中、低WBC组CR率低,死亡率高,差异均有统计学意义(均P<0.05),低WBC组与中WBC组差异无统计学意义(P>0.05).结论 As2O3联合ATRA较单用As2O3治疗初诊APL获得CR时间短,WBC>10×109/L为预后不良的因素,APL分化综合征应尽早发现,及时处理.     

治疗急性早幼粒细胞白血病的几个问题

急性早幼粒细胞白血病(APL)为急性髓系白血病的一个亚型,以进展快,易发生弥散性血管内凝血(DIC)和死亡率高为特征.95%以上APL患者有典型染色体易位t(15;17)形成PMLRARα融合基因.1986年以来,中国首创以全反式维甲酸(ATRA)和亚砷酸(ATO)治疗APL,使APL的转归大大改观,成为仅用药物可治愈的AML.结合作者经验讨论治疗APL中的有关问题.     

MT方案治疗急性单核细胞白血病的疗效及其与染色体核型的关系

目的 研究米托蒽醌联合替尼泊苷(MT)方案在急性单核细胞白血病(M5)诱导缓解中的疗效及患者不良反应,并观察疗效与白血病染色体核型的关系.方法 将33例M5患者按治疗史分两组:初治组23例(A组)、DA(柔红霉素联合阿糖胞苷)或HDA(三尖杉酯碱、柔红霉素和阿糖胞苷)1个疗程无效组10例(B组).按核型预后分两组:预后中等组29例(C组),预后不良组4例(D组),均采用MT方案2个疗程诱导缓解,分别统计4组的临床疗效及患者不良反应.结果 MT方案对A、B组的M5诱导完全缓解(CR)率分别为83%(19/23)及60%(6/10),有效率达91%(21/23)及70%(7/10).C、D组CR率分别为83%(24/29)及25%(1/4),有效率为88%(26/29)及50%(2/4),其中复杂核型CR率为0(0/3),非复杂核型的11q23染色体异常患者一次化疗达CR率100%(4/4).MT方案对M5化疗后白细胞最低点在第(7±3)天出现,为(0.4±0.2)×109/L,白细胞<1×109/L时间达(8±5)d,未见化疗相关死亡病例.结论 MT方案简单有效、较安全,是治疗M5的较佳化疗方案,对1个疗程DA、HDA方案无效者亦可试用.MT方案化疗疗效与核型预后分组有关,对11q23染色体异常的M5患者疗效较好,对复杂核型患者疗效欠佳.     

急性早幼粒细胞白血病的治疗选择:来自2010年美国血液学年会的报道

2010年美国血液学年会(ASH)会议中,与急性早幼粒细胞白血病(APL)治疗相关的文章共有17篇:以全反式维甲酸(ATRA)+常规化疗为主的4篇,以ATRA+三氧化二砷(ATO)为主的2篇,以ATO为主的6篇,与造血干细胞移植相关的3篇,与中枢神经系统白血病相关的2篇.     

三氧化二砷治疗血液病后合并带状疱疹的临床研究

目的 分析三氧化二砷(ATO)治疗血液病后合并带状疱疹感染患者的临床特征及其可能的发生机制.方法 将研究对象分为研究组(应用ATO)和对照组(未应用ATO),观察两组带状疱疹发病率,以及研究组中发生带状疱疹和未发生带状疱疹患者的平均化疗次数.结果 研究组带状疱疹发病率为23.95%(23/96),发生带状疱疹者平均化疗7.60次,未发生带状疱疹者平均化疗7.72次(Z=0.976,P=0.296);对照组带状疱疹发病率7.89%(3/38),两组间带状疱疹发病率差异有统计学意义(χ2=4.492,P=0.034).结论 ATO治疗血液疾病可以增加带状疱疹的发病率,可能与其激活水痘-带状疱疹病毒有关.     

沙利度胺治疗急性白血病的疗效及对血管调控因子水平的影响

目的 观察沙利度胺联合化疗治疗急性白血病的临床疗效及其对血浆血管内皮生长因子(VEGF)、血管内皮生长因子受体(VEGFR)、碱性成纤维细胞生长因子(bFGF)水平的影响.方法 急性白血病患者36例,随机分为试验组及对照组各18例.每组均予以常规化疗方案标准剂量化疗,试验组同时口服沙利度胺100 mg/d.治疗前及治疗后8周分别采集外周血,双抗体夹心酶联免疫吸附法(ELISA)检测血浆VEGF、VEGFR、bFGF含量.以15位健康体检者为健康对照组.结果 试验组与对照组有效率分别为88.9%(16/18)和77.8%(14/18),差异有统计学意义(x2=4.103,P＜0.05).试验组与对照组治疗前血浆VEGF水平分别为(389.78±249.94)和(318.54±125.78)pg/ml,高于健康组的(132.91±26.66)pg/ml(t=3.141、3.024,均P＜0.01);治疗后分别为(211.74±36.72)和(288.02±31.77)pg/ml,高于健康组(t=2.413、2.324,均P＜0.05);试验组与对照组治疗前VEGF差异无统计学意义(t=1.384,P＞0.05),治疗后差异有统计学意义(t=2.793,P＜0.05).试验组与对照组治疗前血浆VEGFR水平分别为(2490.75±1695.9)和(2322.78±1105.87)pg/ml,高于健康组的(1134.98±378.45)pg/ml(t=2.914、2.783,均P＜0.01);治疗后分别为(1359.71±390.24)和(1753.89±337.04)pg/ml,与健康组相比差异有统计学意义(t=2.572、2.447,均P＜0.05);试验组与对照组治疗前VEGFR差异无统计学意义(t=1.276,P＞0.05),治疗后差异有统计学意义(t=2.486,P＜0.05).试验组与对照组治疗前血浆bFGF水平分别为(2.43±0.27)和(2.4l±0.33)ng/ml,高于健康组的(1.83±0.44)ng/ml(t=4.982、4.171,均P＜0.05);治疗后分别为(2.09±0.17)和(2.11±0.31)ng/ml,与健康组相比差异有统计学意义(t=3.01l、2.773,均P＜0.05);试验组与对照组治疗前及治疗后相比差异无统计学意义(t=0.953、1.282,均P＞0.05).结论 沙利度胺联合化疗可提高急性白血病患者的缓解率,有可能成为一种通过抗血管新生从而抑制白血病细胞生长及浸润的有效治疗方法.     

内镜下钛夹联合中西药治疗上消化道穿孔的临床研究

目的:探讨内镜下钛夹联合中西药治疗上消化道穿孔的疗效.方法:将本院临床上胃镜检查诊断为上消化道穿孔的80例患者随机分为观察组(40例)和对照组(40例).观察组采用内镜下钛夹联合中西药治疗,对照组采取传统内科治疗方法.结果:两组有效率(Ⅰ级+Ⅱ级)分别为87.5%和80%,X2=4.258,观察组住院时间均值为9.5±5.2d,与对照组(12.4±4.5d)相比t=2.945,p＜0.05,并发症发生率和再穿孔率也显著低于对照组,X2=3.896,4.013,p＜0.05,提示组间比较存在显著差异性,有统计学意义.结论:内镜下钛夹联合中西药治疗上消化道穿孔的疗效确切,值得临床推广应用.     

Relapsed acute promyelocytic leukemia previously treated with all-trans retinoic acid: clinical experience with a new synthetic retinoid, Am-80

All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.     

Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.     

Treatment of acute promyelocytic leukemia--combined use of all-trans retinoic acid and granulocyte colony-stimulating factor

We evaluated the effect of treatment by all-trans retinoic acid (ATRA) in 9 patients with acute promyelocytic leukemia (APL). Of 6 patients who had circulating leukemic blasts before treatment, 3 initially received ATRA alone but died of respiratory failure due to retinoic acid syndrome (RAS). High dose steroid therapy did not rescue RAS in these patients. Another 3 who were given intensive chemotherapy followed by ATRA and/or granulocyte colony-stimulating factor (G-CSF) achieved complete remission (CR). Of 3 patients without peripheral leukemic blasts before treatment, 1 received intensive chemotherapy followed by G-CSF and reached CR, 1 who had been previously given ATRA did not respond to ATRA, and 1 did not initially respond sufficiently to ATRA alone but responded dramatically to ATRA plus G-CSF. In the treatment of APL, appropriate combination of ATRA, G-CSF and chemotherapy should always be taken into consideration. In addition, RAS have to be carefully avoided when applying ATRA therapy in patients who have circulating leukemic blasts before treatment.     

Treatment results of intermittent and cyclic regimen with ATRA and chemotherapy in childhood acute promyelocytic leukemia. Children's Cancer and Leukemia Study Group

An intermittent and cyclic regimen with All-Trans Retinoic Acid (ATRA) and intensive chemotherapy was conducted due to pharmacokinetic studies on ATRA for acute promyelocytic leukemia (APL) in children. We have treated 17 children with APL using ATRA for remission induction followed by an intermittent schedule of ATRA plus intensive chemotherapy (APL-ATRA protocol). There were 10 males and 7 females. The median age was 9.0 years old. The median baseline white blood cell count was 12.1 x 10(3)/microliter, hemoglobin 7.8 g/dl, platelet 4.5 x 10(4) microliters at diagnosis. Sixteen patients showed t(15; 17) translocation. RT-PCR analysis was available in 15 patients and showed PML/RAR alpha rearrangement in all patients. Overall, 13 or 17 newly diagnosed patients (88%) achieved complete remission and EFS was 67%. Compared to the control (same chemotherapy without ATRA regimen), remission induction and EFS were significantly increased. The toxicity of ATRA consisted of retinoic acid syndrome in 1 and pseudotumor cerebli in another. Other toxicities included headache, chelitis, gastrointestinal trouble and bone pain. These results suggest that intermittent and cyclic regimen with ATRA and intensive chemotherapy (APL-ATRA protocol) is highly effective for APL patients.