亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床观察

目的 探讨亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床疗效.方法 28例急性早幼粒细胞白血病患者随机分为治疗组及联合组,其中治疗组患者采用亚砷酸进行诱导缓解治疗,联合组患者采用全反式维甲酸联合亚砷酸进行诱导缓解治疗.结果 2组患者治疗后其完全缓解例数差异无统计学意义(P>0.05),但达完全缓解的时间差异有统计学意义(P<0.05),2组患者出现并发症的机会差异无统计学意义(P>0.05).结论 对急性早幼粒细胞白血病患者采用亚砷酸联合全反式维甲酸进行诱导缓解治疗,可降低患者并发症的发生并缩短患者到达完全缓解的时间.     

全反式维甲酸联合三氧化二砷治疗初发急性早幼粒细胞白血病的近期疗效分析

目的分析全反式维甲酸与三氧化二砷联合治疗初发急性早幼粒细胞白血病的近期疗效。方法随机将我院2012年10月至2015年10月收治的90例初发急性早幼粒细胞白血病患者分为两组各45例,对照组患者给予全反式维甲酸治疗,观察组患者联合全反式维甲酸和三氧化二砷进行治疗,比较两组患者的近期疗效。结果观察组CR率为88.9%,对照组CR率为71.1%,比较具有统计学差异(P<0.05);观察组和对照组患者达CR时间、白细胞峰值及PML/RARα转阴率的对比具有统计学差异(P<0.05)。结论联合三氧化二砷与全反式维甲酸治疗急性早幼粒细胞白血病的近期疗效明显,值得临床推广和运用。     

中剂量激素抢救维甲酸综合征一例

维甲酸综合征是全反式维甲酸（ATRA）治疗急性早幼粒细胞白血病时出现的严重药物不良反应，国内相关报道较少。我们成功抢救1例维甲酸综合征患者，报告如下。 1病历摘要 患者男，42岁。因确诊急性早幼粒细胞白血病3年多，皮肤紫癜2d、第2次复发于2007年8月15口收住院。3年前患者凶皮肤出血点、紫癜入院。结合外周血常规、骨髓常规及组织化学等检查确诊急性早幼粒细胞白血病。     

全反式维甲酸、亚砷酸和柔红霉素方案治疗初诊急性早幼粒细胞白血病观察

目的探讨全反式维甲酸、亚砷酸和柔红霉素方案治疗初诊急性早幼粒细胞白血病的临床效果。方法选择桂林市医学院附属医院2005年1月至2010年1月急性早幼粒细胞白血病触诊患者32例,将上述患者分为两组,观察组和对照组。观察组患者给予亚砷酸10mg加入生理盐水500mL中静脉滴注,每天1次,连续用药到患者为完全缓解;给予全反式维甲酸每天30~60mg口服;给予柔红霉素每天20~40mg,在第1~3天和第15~17天静脉注射。对照组患者给予全反式维甲酸每天30~60mg口服。结果观察组治疗1周后早幼粒细胞和白细胞总数分别与对照组比较,差异有统计学意义(P<0.05);两组完全缓解率比较,差异有统计学意义(P<0.05)。结论全反式维甲酸、亚砷酸和柔红霉素方案能够显著提高初诊急性早幼粒细胞白血病完全缓解率,临床效果显著。     

全反式维甲酸协同治疗急性单核细胞白血病的初步报告

根据维甲酸(RA)能诱导人白血病细胞株HL—60和急性早幼粒细胞白血病(APL)患者的新鲜血白血病细胞分化成熟的体外研究结果,我们最近用国产全反式维甲酸协同其它联合化疗方案,对3例骨髓增生低下并处于粒细胞缺乏状态的急性单核细胞白血病(M_3)老年患者进行治疗,2例取得显著疗效,现报告于下。     

三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病29例

目的观察三氧化二砷（As2O3）联合全反式维甲酸（ATRA）治疗急性早幼粒细胞白血病（APL）的疗效及毒副反应。方法患者使用三氧化二砷联合全反式维甲酸双诱导治疗,对高白细胞患者加用单一化疗药物高三尖衫酯碱（H）或柔红霉素（DNR）,合并弥漫性血管内凝血（DIC）患者予以输注血浆／纤维蛋白原。结果29例患者中26例完全缓解,完全缓解（CR）率89．66％;3例死于颅内出血。结论三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病的疗效确切,患者耐受性较好。     

砒霜·白血病

用全反式维甲酸和三氧化二砷联合治疗急性早幼粒细胞白血病,患者5年无病生存率可达到90％以上,是目前国际上治疗急性早幼粒细胞白血病所取得的最好疗效。这一创新的治疗方案被国际社会称为“上海方案”,成为整个肿瘤治疗领域的典范。     

甘露聚糖肽序贯联合化疗治疗急性早幼粒细胞白血病的临床观察

目的观察甘露聚糖肽序贯与全反式维甲酸、三氧化二砷联合化疗治疗急性早幼粒细胞白血病的临床疗效及安全性。方法选择我院肿瘤血液科2003年1月至2007年12月初诊为急性早幼粒细胞白血病患者60例,随机分为治疗组、对照组、空白组,每组20例,3组患者均采用全反式维甲酸、三氧化二砷联合化疗法,治疗组患者在住院期间加用甘露聚糖肽注射液,出院后口服甘露聚糖肽口服液,对照组患者住院期间加用胸腺肽注射液,出院后口服胸腺肽肠溶片,空白组患者住院期间静脉滴注同体积的氯化钠注射液,出院后口服等量的安慰剂。结果治疗组患者总有效率为90%,与对照组、空白组比较差异均有统计学意义(P值<0.05)。治疗组患者胃肠道反应如恶心、呕吐发生率为30%,中性粒细胞、血小板等骨髓抑制反应发生率为25%,肝功能异常率为10%,其中胃肠道反应发生率、骨髓抑制反应发生率均较对照组、空白组显著降低(P<0.05)。随访发现,治疗组5年无病生存率、5年生存率均显著高于对照组、空白组(P<0.05)。结论甘露聚糖肽序贯与全反式维甲酸、三氧化二砷联合化疗治疗急性早幼粒细胞白血病,不仅能显著提高临床疗效,降低不良反应发生率,还能延长患者生存期。     

全反式维甲酸治疗急性早幼粒细胞白血病五例临床分析

近年来,国内外应用全反式维甲酸(RA)治疗急性早幼粒细胞白血病(APL)均获得良好疗效。我院自1988年以来应用 RA(由上海瑞金医院提供)治疗 APL 5例亦取得较满意疗效,并获得骨髓完全缓解,报告如下。     

全反式维甲酸治疗急性早幼粒型白血病的临床和实验研究

应用国产全反式维甲酸治疗急性早幼粒白血病患者,并同时进行骨髓原代培养细胞的体外诱导分化、正常粒单造血祖细胞集落检测、白血病原始细胞集落检测和白血病细胞核型R显带分析等实验研究。结果表明:维甲酸的疗效是通过使白血病细胞向终末期定向分化而丧失增殖能力来实现的。本组患者的骨髓完全缓解率达92.5％,但部分患者仍易复发。以传统化疗达到完全缓解的患者在复发后,维甲酸可以使患者再次达到完全缓解;但以维甲酸治疗达到完全缓解的患者复发后,第二次用维甲酸的疗效即显著降低,甚至完全无效。     

肝脂素对急性白血病骨髓基质细胞造血调控作用的研究

目的研究肝脂素对急性白血病骨髓基质细胞造血的调控作用。方法ELISA法检测细胞因子,光镜观察骨髓基质细胞形态。结果肝脂素可选择性作用于急性白血病骨髓基质细胞,使网状细胞转变为小梭形正常基质细胞。抑制急性白血病基质细胞集落的生长,使ALL与AML基质细胞集落生长情况与正常趋向一致,ALL与AML的TNFα分泌明显下降(P<0.05),AML的IL-6明显下降(P<0.01),IL-1升高。结论肝脂素能诱导急性白血病造血微环境中的基质细胞向正常转化,发挥正常造血调控作用,为急性白血病的脂类治疗提供了一种新的方法。     

全反式维甲酸-正丁酸（丙戊酸）前体药物的设计、合成及抗肿瘤活性研究

目的合成全反式维甲酸（ATRA）的前体药物，增强ATRA对急性早幼粒白血病（APL）细胞的分化诱导作用。方法以乙二醇、对苯二酚、乙醇胺及乙二胺等为连接物，通过酯键和酰胺键将分化诱导剂ATRA与组蛋白去乙酰酶（mAC）抑制剂正丁酸、丙戊酸连接起来，形成前体药物。结果合成了13个ATRA与正丁酸或丙戊酸相连接的前体药物，化合物的结构经^1H-NMR、MS和IR确证。结论考察部分化合物对急性早幼粒细胞白血病细胞株NB4的生长抑制作用和对急性早幼粒白血病（APL）细胞分化诱导作用，初步的药理实验结果表明，ATRA与丙戊酸通过酰胺键连接时，对NB4细胞分化诱导能力显著增加。     

Tamibarotene

Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials. Clinical trials held in Japan showed that tamibarotene had efficacy in APL patients who had relapsed from ATRA-induced complete remission. Recently, better understanding of the various mechanisms of action of retinoids has stimulated great interest in its potential use for treatment of various diseases. Tamibarotene is being investigated for treatment of multiple myeloma and Crohn's disease in clinical trials. This review focuses on tamibarotene's mechanisms of action, chemical properties, pharmacokinetics and its use in APL as well as its potential use in various disorders.     

急性早幼粒细胞白血病46例临床分析

目的：总结46例急性早幼粒细胞白血病（APL）的治疗、预后及不良反应,以达到提高缓解率,延长生存期的目的。方法：对46例APL患者治疗期间应用全反式维甲酸、亚砷酸、DA/MA/HA及复方黄黛片进行联合治疗。结果：本组46例APL患者除2例早期死亡外,其余44例均达到完全缓解（CR）,CR率为95.7%。结论：应用全反式维甲酸、亚砷酸及复方黄黛片联合治疗APL是安全有效的,对初治或复发患者均具有疗效高、耐受性好的特点。     

Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid

We report the first case of granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia (APL). Acute renal failure during treatment with ATRA has been previously reported as a part of an ATRA syndrome or a thrombotic complication of a hypercoagulable state. This case indicates an alternative mechanism of acute renal failure occurring during ATRA therapy.     

The use of hematopoietic growth factors in the treatment of acute leukemia

Cytokines are centrally involved in the regulation of normal hematopoiesis, the production of mature blood cells by bone marrow stem cells. Cytokines influence stem survival, proliferation, and differentiation commitment, as well as controlling the orderly maturation of progenitor cells into functional leucocytes, erythrocytes, and platelets. Acute leukemias result from malignant transformation of bone marrow stem cells. Although cytokines do not appear to be centrally involved in the pathogenesis of acute leukemias, leukemic cells express receptors for many of the cytokines regulating normal hematopoiesis, particularly G-CSF, GM-CSF, IL-3, and stem cell factor. These molecules have demonstrable effects on acute leukemia cells in vitro, inducing proliferation and enhancing survival, but their biological activity when administered as recombinant proteins in pharmaceutical doses to patients with active leukemia are less well understood. Because of the stimulatory effects of cytokines such as G-CSF and GM-CSF on normal hematopoiesis in vitro and in normal individuals, these two molecules have been extensively studied in randomised clinical trials of chemotherapy for cancer, including acute leukemia. Concerns about the potential for G-CSF and GM-CSF to accelerate the growth of acute myeloid leukemia, which expresses receptors for both molecules, have not been realised. Conversely, the concept of using either of these two cytokines to induce acute myeloid leukemia cells into active DNA synthesis, thus potentially sensitising them to the effects of S-phase-specific drugs, has not been shown to be clinically beneficial. Both G-CSF and GM-CSF have been demonstrated to accelerate the recovery of normal granulopoiesis after intensive initial cytotoxic chemotherapy for acute leukemia, significantly shortening the duration of severe treatment-induced neutropenia, and resulting in a number of tangible benefits including reduction in infection, use of intravenous antibiotics, and duration of hospital stay. However, the final role for these agents in the treatment of acute leukemia remains controversial and still to be fully defined.     

Cytoplasm prepared from all-trans retinoic acid (ATRA)-treated human hematopoietic progenitor cells induces differentiation of both ATRA sensitive and ATRA resistant leukemia cells

In this study, hematopoietic cells from human placental blood were treated with the differentiation-inducing drug all-trans retinoic acid (ATRA). Their cytoplasm was then used to culture the human myelogenous leukemia cell line HL60, NB(4) cells and the RA-resistant HL60-R and NB(4)-R(2) cells. All of these four kinds of leukemia cells underwent macrophage/monocyte differentiation and apoptosis, while their proliferation was inhibited. This suggests that the RA receptors were not essentially needed in this situation, and this method should be applicable in the treatment of RA-resistant promyelocytic leukemia as well as other kinds of leukemia.     

亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床分析

目的探讨亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床效果。方法将本院2008年1月～2013年9月收治的64例急性早幼粒细胞白血病患者随机分为4组,每组各16例。联合组给予亚砷酸和全反式维甲酸进行双诱导治疗,亚砷酸组给予亚砷酸治疗,维甲酸组给予全反式维甲酸治疗,化疗组给予常规化疗治疗。结果联合组、亚砷酸组的所有患者（100％）完全缓解,无死亡病例,维甲酸组13例（81．2％）患者达到完全缓解,1例死亡,化疗组仅6例（37．5％）完全缓解,2例死亡,前3组的完全缓解率均显著高于化疗组（P〈0.05）;联合组患者用药至完全缓解的时间明显短于亚砷酸组、维甲酸组（P〈0.05）;联合组患者凝血指标恢复正常所用的时间短于亚砷酸组、维甲酸组（P〈0.05）;肝功能损伤情况：联合组最严重,亚砷酸组次之,维甲酸组较轻,化疗组最轻（P〈0.05）,化疗组的胃肠道反应、皮肤损伤情况较严重,受影响患者明显多于其他3组（P〈0.05）。结论亚砷酸联合维甲酸治疗急性早幼粒细胞白血病短期效果显著,完全缓解率高,并可缩短患者的完全缓解时间。     

维甲酸和亚砷酸双诱导联合化疗对初诊急性早幼粒细胞白血病的治疗效果

目的观察维甲酸和亚砷酸双诱导联合化疗对急性早幼粒细胞白血病的临床治疗效果。方法将收录的52例急性早幼粒细胞白血病患者随机的分为4组,A组13例患者采取维甲酸和亚砷酸双诱导联合化疗;B组13例患者采取维甲酸联合化疗;C组13例患者采取亚砷酸联合化疗;D组13例患者采取化疗,观察4组的治疗效果。结果通过4组的治疗效果分析,A组患者的症状完全缓解率明显的高于B、C、D三组的情况,并且病死率也明显的低于C、D组的情况,比较具有明显的差异(P<0.05),统计学有意义;A组患者的高白细胞血症的持续时间与症状缓解时间均明显的低于B、C、D组的情况,比较具有明显的差异(P<0.05),统计学有意义。结论对初诊急性早幼粒细胞白血病患者采取维甲酸和亚砷酸双诱导联合化疗治疗效果明显,而且治疗更准确,可靠性强,值得临床中应用。