Mylotarg治疗第一次复发的CD33^＋急性髓系白血病患者的疗效和安全性

Mylotarg(Gemtuzumab Ozogamicin,CMA-676)是人源化抗CD33单克隆抗体与抗肿瘤抗生素Calicheamicin偶联而成的一个新的抗体导向化疗药药。作者报告单用该药治疗第一次复发未治CD33~+急性髓系白血病(AML)的疗效及安全性。 方法 北美及欧洲多中心研究观察142(男84、女58)例,CD33~+AML(CD33~+白血病细胞大于80％)第一次复发患者,中位年龄61(22～84)岁。Mylotarg每次9mg/m~2,持续静滴2h,每次用药间隔不少于14天,不超过28天,最多     

老年急性髓细胞白血病的治疗进展

老年急性髓细胞白血病(AML)多起源于更早期的造血祖细胞，具有不良的预后遗传学特征，且因年龄大、主要脏器功能衰退，治疗和预后不佳，病死率高。因此近年来老年AML治疗逐渐成为关注热点。     

美罗他格——CD33单抗偶联物治疗急性髓细胞白血病

CD33抗原大量表达于急性髓细胞白血病(AML)细胞表面,可成为靶向免疫治疗的目标。美罗他格是人源化抗CD33单克隆抗体与强效抗肿瘤抗生素——乙酰棘孢霉素偶联物,与髓性白血病细胞表面CD33抗原结合,进入细胞后释放棘孢霉素,对髓细胞白血病细胞有明显杀灭作用,用于治疗复发、难治的CD33 AML,获得良好疗效,与其它化疗药物联合应用治疗AML的临床试验正在进行中。美罗他格的耐受性一般较好,但肝脏毒性及肝静脉阻塞综合征等毒副反应值得关注。美罗他格的耐药机制可能来自多方面,其中包括P-糖蛋白介导的药物排出等。     

分子靶向治疗在急性髓系白血病中的研究进展

急性髓系白血病(acute myeloid leukemia, AML)是一种高度异质性的血液系统恶性肿瘤,常规治疗以细胞毒药物化疗为主,但总体疗效不理想,5年生存率不到30%。近年来随着对AML发病机制及基因突变认识的逐渐深入,一系列新型分子靶向药物相继问世。这些药物明显改善了AML患者的预后,为AML患者提供更多的治疗选择。本文就分子靶向治疗在AML中的研究进展作一综述。     

老年急性髓系白血病的治疗问题

急性髓系白血病（ＡＭＬ）是常见的造血系统恶性肿瘤,老年人易患。流行病学调查显示,除了儿科病例,老年人群ＡＭＬ发病率比总的人群发病率高出数倍［１］。近年来在ＡＭＬ治疗方面已有长足进展,但老年患者受益不多。首先,现有化学治疗用于老年ＡＭＬ的缓解率低,缓解时间短。如用标准的ＤＡ诱导化疗方案,即柔红霉素４５～６０ｍｇ／ｍ２连续３ｄ和阿糖胞苷（Ａｒａ－Ｃ）ｌ００～２００ｍｇ／ｍ２连续７ｄ,治疗老年ＡＭＬ的完全缓解（ＣＲ）率通常为４０％～６０％,低于一般成年人的ＣＲ率（６０％～７５％）。而且不论使用何种巩固…     

老年CD+56急性髓系白血病临床生物学特征

目的 研究CD+56老年急性髓系白血病(AML)的临床生物学意义.方法 对102例初治老年AML进行细胞形态学、免疫表型、多药耐药P糖蛋白(PgP)检测,并常规采用HAE方案诱导治疗,判定疗效.结果 老年急性髓系白血病,CD56阳性率39.22%.CD+56AML在FAB分型中以M2b、M5、M7多见,高白细胞计数(57.03×109/L vs 33.65×109/L,P=0.047),多表达PgP(62.50% vs 40.32%,P=0.042).CD+56AML患者髓外浸润现象明显(62.50% vs 37.09%,P=0.015),尤其是脾脏(42.50% vs 19.35%,P=0.014)显著受累,CD56表达与年龄、性别、血红蛋白含量、血小板计数及外周血幼稚细胞数无关,也不影响CR率(P值分别为0.306,0.840,0.564,0.302,0.686,0.547),但无病生存时间(DFS)(5.75个月 vs 30.00个月,P=0.048)和总生存时间(OS)(5.34个月 vs 22.03个月,P=0.032)较短.结论 CD+56AML具有独特的临床生物学特征,多表达耐药蛋白PgP,生物学侵袭性较强,生存期短,预后较差.建议初诊时监测CD56分子表达以判断预后.     

急性髓系白血病的治疗试验

美国国立癌症研究所(NCI)1988年8月26日组织了一次急性髓系白血病(AML)诊断和疗效标准专题讨论会，旨在规范AML临床试验的设计标准。随着对AML细胞生物学、遗传学、分子生物学特征认识的不断深入，此外，不同作用和毒理机制的新药不断发现，有必要对1988年提出的美国NCIAML诊断和疗效判断标准进行修订，为此，2001年5月23-25日在西班牙的马德里举行了一个国际工作组会议并提出了“国际工作组关于AML治疗试验的诊断、疗效标准的标准化、治疗结局和报告标准的修订建议”。     

老年急性髓系白血病的治疗现状

急性髓系白血病（AML）随着年龄的增长发病率逐渐升高。由于老年AML患者化疗完全缓解率低,治疗相关死亡率高,长期生存率低,预后差,尚缺乏统一有效的治疗策略。本文就目前老年AML治疗现状作简单综述,探讨传统化疗、造血干细胞移植及新的靶向药物在老年AML治疗中的应用。     

急性髓系白血病治疗后转型二例

例 1,男性 ,3 7岁 .因反复皮肤瘀点 ,牙龈出血伴乏力 10 d入院。曾在当地医院因贫血、血小板减少就诊。病程中无发热、骨痛。既往无特殊病史。查体 :T3 7.8℃ ,贫血貌 ,全身皮肤见散在瘀点、瘀斑 ,咽部稍红 ,浅表淋巴结不大 ,胸骨无压痛 ,心肺查体无异常发现 ,腹软 ,肝脾未触及 ,双下肢不肿。实验室检查 :WBC 15 .0× 10 9/ L ,Hb 78g/ L ,plt 2 0× 10 9/ L ;骨髓增生明显活跃 ,异常早幼粒细胞 0 .70 ;染色体发现存在 t( 15 ;17)易位。确诊为 ANL L - M3。应用全反式维甲酸 ( ATRA) 3 0 mg/ d达 CR,经Acla+ Ara- c(阿克拉霉素、阿…     

Critical pathway for the treatment of acute myelogenous leukemia

Based on analysis of data from 10 patients newly diagnosed as having acute myelogenous leukemia (AML), we developed a critical pathway (CP) to prevent infection and thus shorten the period of hospitalization. This CP shows laboratory test results, vital signs, chemotherapy regimen, concomitant supportive care and oral medications, gargling with antiseptic mouthwash, other anti-infection measures, diet, room conditions, patient education in anti-infection measures, outcome, and variance on the vertical axis and time on the horizontal axis. After introduction of the CP, 9 of the newly diagnosed AML patients did not experience severe treatment-related complications during a mean hospitalization of 29 days until remission and 95 days until discharge. These results suggest that the present CP makes it possible to shorten the hospital stay, reduce treatment costs, and improve the quality of life of AML patients.     

老年急性髓系白血病个体化治疗探讨

目的:探讨老年急性髓系白血病(AML)个体化治疗方案。方法:对我院1994~2005年收治老年AML患者(≥60岁)77例进行回顾性分析。根据化疗剂量将患者分为A(亚标准剂量)、B(减量化疗)及C(支持化疗)3组,并对3组的临床特征和治疗效果进行比较。结果:可评价患者A组45例,B组9例,C组9例。A组CR率高于B组(P<0.05),分别为53.3%和44.4%;平均生存期显著延长(P<0.05),分别为258、195d。但白细胞化疗后最低值A组要明显低于B组(分别为0.8×109/L,4.5×109/L),骨髓抑制时间明显延长(分别为19,13d),不良反应发生率明显增高(分别为97.8%,77.8%)。C组患者平均生存期231d,生存期与其他2组均差异无统计学意义(均P>0.05),但平均住院日明显缩短(P<0.05)。结论:老年AML对化疗反应差,缓解率低,生存期短,治疗方案宜个体化。     

C-kit as a target in the treatment of acute myelogenous leukemia

Acute myelogenous leukemia (AML) is a difficult disease to treat. Novel treatment strategies, including molecular targeted therapy, are currently being explored. The c-kit receptor represents a potential therapeutic target for AML. The receptor is expressed on more than 10% of blasts in 64% of de novo AMLs and 95% of relapsed AMLs. C-kit mediates proliferation and anti-apoptotic effects in AML. This review will discuss the biology of c-kit in normal and malignant hematopoiesis, and the recent clinical trials targeting c-kit in AML.     

Progress and controversies in the treatment of pediatric acute myelogenous leukemia

The outcome for children and adolescents with acute myelogenous leukemia (AML) has substantially improved during the past several decades, such that nearly 50% of these patients can be cured. A significant part of this improvement has occurred over the past 10 years, during which time, dose intensification has played a much greater role in therapeutic strategies. Although dose intensification increased the cure rate for pediatric patients with AML, there has also been increased treatment-related morbidity and mortality. Further, despite such toxicity, the primary cause of death is still leukemia. This article outlines some of the different strategies leading to our current treatments and presents several questions and controversies. These questions lead to what future therapeutic options and approaches will be pursued.     

Mitoxantrone in the treatment of acute myelogenous leukemia: a review

Mitoxantrone is an intravenous anthracenedione structurally related to the anthracycline antibiotics. This drug has been used for several years in the treatment of acute myelogenous leukemia (AML). Its use has been based on its pharmacological properties, its incomplete cross-resistance with other intercalating agents, and its better tolerance as predicted by preclinical studies. Various treatment schedules, using mitoxantrone alone and in combination with other anti-leukemic agents, have been used in clinical trials. Complete remission (CR) rates ranged from 14 to 44% in refractory AML and from 46 to 79% in relapsed patients. Although a superiority of mitoxantrone over anthracyclines has not been clearly demonstrated in newly diagnosed patients, mitoxantrone is now recognized as a useful drug in first line therapy. The tolerability profile of mitoxantrone indicates that it offers patients an acceptable quality of life compared with standard treatment regimens, and could be a good alternative to the anthracyclines. The development of new therapeutic concepts aiming at an optimization of its use is now in process and first results are promising.     

Hypocholesterolemia in acute myelogenous leukemia

Plasma-cholesterol concentrations were determined in 85 acute myelogenous leukemia patients. Measurements were repeated in 28 cases during remission. Mean plasma-cholesterol concentration (+/- SD) at diagnosis was 3.95 mmol/l (+/- 1.29). 47 patients (55.3%) had hypocholesterolemia (less than 3.87 mmol/l). Among the main clinical, hematologic and biochemical parameters, only high leukocyte counts were correlated with hypocholesterolemia. As far the FAB subtypes are concerned, the lowest cholesterol levels were observed in leukemias with monocytic component. However, although the same FAB subtypes showed significantly higher leucocytes counts than the other subtypes, both parameters were independently related to low cholesterol levels. Remission was associated with a significant increase in cholesterol levels in those patients with low cholesterol concentrations or high leukocyte counts at diagnosis. These results support the idea that initial hypocholesterolemia in acute myelogenous leukemia is related to the tumoral mass present at diagnosis.     

The role of immunotherapy in acute myelogenous leukemia

The use of immunotherapy for acute myelogenous leukemia (AML) is controversial. Twenty-four trials have been reported in which 1,491 patients with AML received various forms of immunotherapy, including BCG, methanol extract residue (MER) of BCG, or Corynebacterium parvum. Some patients were immunized with allogeneic or autologous leukemia blast cells. In only four of the 24 trials was a significant prolongation of remission reported. Pooled data from all 24 studies were analyzed further. No statistically significant difference in duration of remission between patients who received maintenance chemotherapy alone and those who received maintenance chemotherapy plus immunotherapy was found. A significant survival advantage for those patients who received BCG and chemotherapy for maintenance therapy was detected. A beneficial biologic effect for the patients treated with BCG is suggested but this was not a disease-free survival advantage, and had no impact on cure of patients with AML. Immunotherapy, as currently conceived, seems to have no substantial benefit for patients with AML receiving optimal chemotherapy.