亚砷酸联合维甲酸治疗急性早幼粒细胞白血病的疗效和观察

目的探讨亚砷酸联合维甲酸治疗急性早幼粒细胞白血病的疗效。方法将45例急性早幼粒细胞性白血病患者随机分为双诱导组(亚砷酸联+维甲酸)、维甲酸组、常规化疗组,观察各组白细胞总数、早幼粒细胞、缓解时间和药物不良反应。结果双诱导组治疗1周后早幼粒细胞比率、白细胞总数、CR与维甲酸组、常规化疗组比较,差异有显著性(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疗效显著,完全缓解率高。     

Acute promyelocytic leukemia: current strategies for the treatment of newly diagnosed disease

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia that comprises about 10% of cases. It is characterized by the accumulation of granulocytic cells blocked at the promyelocytic stage of differentiation in the bone marrow and the peripheral blood, life-threatening coagulopathy, and a remarkable response to treatment with all-trans-retinoic acid (ATRA), arsenic trioxide, and anthracyclines. Current treatment strategies with ATRA and anthracycline-based chemotherapy has dramatically transformed APL into the most curable of all acute leukemias. Advances in supportive care together with the early recognition of treatment-related complications have also contributed significantly to increased cure rates. In this review we explore current treatment strategies in the management of newly diagnosed APL. We also highlight practical points that may serve as a guideline for the treating physician and address current controversies in the choice of treatment.     

Complete Atrioventricular Block after Arsenic Trioxide Treatment in an Acute Promyelocytic Leukemic Patient

A V block after arsenic trioxide (As₂O₃) treatment for refractory acute promyelocytic leukemia is very rare. In this patient, the block was at A-H level and manifested with complete AV block and Wenckebach second-degree type 3:2 block. The junctional recovery time during complete AV block did not significantly prolong after administration of more arsenic trioxide. The effect of heart block of arsenic trioxide seemed reversible after the discontinuation of arsenic trioxide and was not correlated to the leukemic status as observed in this patient.     

急性早幼粒细胞白血病的治疗

急性早幼粒细胞白血病(APL)是急性髓细胞白血病的一种特殊亚型.全反式维甲酸(ATRA)的应用使其从一种高度凶险的疾病转变成为一种高度可治愈的疾病.三氧化二砷(ATO)在治疗复发难治性APL取得成功后,也逐渐被引入APL的一线诱导治疗.危险度分层治疗的提出、口服砷剂的使用进一步提高了APL的疗效.本文就APL的治疗现状及其最新进展进行简要综述.     

三氧化二砷应用于淋巴瘤的基础及临床研究进展

三氧化二砷治疗急性早幼粒细胞白血病取得成功后又被实验性用于淋巴瘤的治疗，近年来国内外学者在此方面做了大量研究工作，发现三氧化二砷通过多种途径发挥抗淋巴瘤效应，且很多物质能够增强或减弱这种效应，三氧化二砷治疗对其他化疗药物不敏感的复发及难治性淋巴瘤仍有一定效果且毒副作用小，提示三氧化二砷是一种极具潜力的治疗淋巴瘤的新型药物，现就相关基础及临床研究成果进行综述，     

伴Ph染色体阳性的急性早幼粒细胞白血病诊治反思

目的探讨伴Ph染色体阳性急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)的临床特征及诊治措施,以减少误诊误治。方法回顾性分析我院收治的1例骨髓形态、免疫组织化学及免疫表型极似急性粒单核细胞白血病且Ph染色体阳性APL的临床资料。结果本例因发热3周余就诊,根据骨髓形态学、免疫组织化学及免疫分型结果,初诊为急性粒单核细胞白血病,给予标准IDA方案(伊达比星加阿糖胞苷)化学治疗效果不佳。复查骨髓形态学并结合细胞遗传学检查,确诊为伴Ph染色体阳性APL,经维A酸(ATRA)联合三氧化二砷(ATO)治疗达完全缓解(CR),巩固治疗4个疗程。随访8个月仍处于CR,PML-RARA融合基因转阴,但BCR-ABL融合基因仍阳性。结论细胞遗传学检查应作为拟诊急性白血病患者的必要检查,可减少误诊,提高治疗效果。     

三氧化二砷和阿糖胞苷交替治疗急性早幼粒细胞性白血病的护理

目的 :总结三氧化二砷和阿糖胞苷交替治疗急性早幼粒细胞性白血病 (M3 )的护理经验。方法 :对 2 1例M3 患者进行三氧化二砷和阿糖胞苷交替治疗并采取有效的护理措施。结果 :2 1例M3 患者治疗总有效率95 2 4 % ,3年生存率 71 4 3% ,5年生存率 5 7 14 % ,生存质量明显提高。结论 :熟悉三氧化二砷和阿糖胞苷的药理作用、药物动力学特点及M3 病理生理特点 ,积极采取有针对性的护理措施有利于提高患者生存率和生存质量。     

Current status and future prospects of nanomedicine for arsenic trioxide delivery to solid tumors

Despite having a rich history as a poison, arsenic and its compounds have also gained a great reputation as promising anticancer drugs. As a pioneer, arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Many in vitro studies suggested that arsenic trioxide could also be used in the treatment of solid tumors. However, the transition from bench to bedside turned out to be challenging, especially in terms of the drug bioavailability and concentration reaching tumor tissues. To address these issues, nanomedicine tools have been proposed. As nanocarriers of arsenic trioxide, various materials have been examined including liposomes, polymer, and inorganic nanoparticles, and many other materials. This review gives an overview of the existing strategies of delivery of arsenic trioxide in cancer treatment with a focus on the drug encapsulation approaches and medicinal impact in the treatment of solid tumors. It focuses on the progress in the last years and gives an outlook and suggestions for further improvements including theragnostic approaches and targeted delivery.     

Arsenic trioxide as effective therapy for relapsed acute promyelocytic leukemia

The standard of treatment for newly diagnosed patients with acute promyelocytic leukemia (APL) is all-trans retinoic acid (ATRA) plus anthracycline-based cytotoxic chemotherapy, a combination that is highly effective for remission induction. However, 20%-30% of patients relapse and require salvage therapy. Reports from China on the striking efficacy and safety of arsenic trioxide in patients with APL led to clinical trials in the United States, which culminated in U.S. Food and Drug Administration approval in September 2000. Trisenox (Cell Therapeutics, Inc., Seattle, WA) is an injectable formulation of arsenic trioxide indicated in the treatment of refractory or relapsed APL. The common side effects of Trisenox therapy are mostly mild and self-limiting and do not require interruption of therapy. Serious adverse effects that can occur include hyperleukocytosis, electrocardiographic abnormalities, and APL differentiation syndrome. These effects can be prevented or managed successfully with careful patient monitoring during treatment. Trisenox has no known cross-resistance with ATRA or other anticancer agents. It does not cause hair loss and is not myelosuppressive in patients with APL. Oncology nurses can play a major role in educating patients about this new drug, explaining its clinical benefits and side effects and the precautions that are necessary for its use.     

Successful treatment of acute promyelocytic leukemia in a patient undergoing hemodialysis with arsenic trioxide

A man undergoing hemodialysis was diagnosed with acute promyelocytic leukemia (APL). He received arsenic trioxide as a single agent and achieved complete molecular remission without severe adverse events. Arsenic trioxide can be used safely and effectively for patients with APL under hemodialysis.     

Successful treatment of acute promyelocytic leukemia in a patient under hemodialysis with arsenic trioxide

A man with chronic kidney disease (CKD) under hemodialysis was diagnosed with acute promyelocytic leukemia (APL). He received arsenic trioxide as a single agent and achieved complete molecular remission without severe adverse events. Arsenic trioxide (ATO) can be used safely and effectively for APL with CKD.     

Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia

In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers differentiation while arsenic trioxide (arsenic) induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, these two drugs both induce the catabolism of the oncogenic promyelocytic leukemia (PML)/RARalpha fusion protein. While APL cell lines resistant to one agent are sensitive to the other, the benefit of combining RA and arsenic in cell culture is controversial, and thus far, no data are available in patients. Using syngenic grafts of leukemic blasts from PML/RARalpha transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival. Furthermore, combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold, associating the two drugs leads to tumor clearance after a 9-mo relapse-free period. These studies establishing RA/arsenic synergy in vivo prompt the use of combined arsenic/RA treatments in APL patients and exemplify how mouse models of human leukemia can be used to design or optimize therapies.     

全反式维甲酸与三氧化二砷治疗急性早幼粒细胞白血病疗效观察

目的：探讨全反式维甲酸(ATRI)与三氧化二砷(As2O3)并用治疗7例初治急性早幼粒细胞白血病(APL)的疗效及副反应。方法：7例采用ATRI 30mg--60mg／d，0．1％As2O3 10mg溶于15％葡萄糖500ml持续滴注3—4小时，30天为1疗程。结果：7例中6例于34天左右CR，未出现明显高白细胞综合症及维甲酸综台症，肝肾损害轻，无病生存期长，结论：ATRI与As2O3并用治疗初治APL疗效好，副反应少，无病生存期长。     

CNS relapses of acute promyelocytic leukemia after all-trans retinoic acid

OBJECTIVE: To review the role of all-trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL). CASE SUMMARY: A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia-retinoic acid receptoralpha (PML-RARalpha) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RARalpha fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood. DISCUSSION: APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85-95% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30-40%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966-January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS. CONCLUSIONS: The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.     

联合三氧化二砷序贯治疗急性早幼粒细胞白血病临床观察

目的:观察三氧化二砷(As2O3)序贯治疗急性早幼粒细胞白血病(acute promyelocytic leuk-emia,APL)的疗效.方法:8例初发APL患者经维A酸诱导缓解后,再予DA方案(柔红霉素、阿糖胞苷)、维A酸和As2O3序贯巩固强化治疗3年,观察持续缓解时间及As2O3的不良反应.结果:8例中,7例随访4～42个月,1例失访.随访的7例均处于完全缓解中,中数缓解时间为17个月.随访超过24个月者3例,仍持续缓解,持续缓解时间最长者已达42个月.此疗法不良反应轻.结论:联合As2O3序贯治疗APL,疗效良好,有望延长APL患者的持续缓解时间及无病生存时间.     

Acute promyelocytic leukemia: an overview with implications for oncology nurses

Acute promyelocytic leukemia (APL), once described as the form of leukemia with the highest mortality, is now the most potentially curable subtype of adult acute myeloid leukemia. A brief review of the history of APL will describe the advances in research and clinical practice and their impact on patient outcomes. Oncology nurses should familiarize themselves with the nuances of APL because of the critical role nurses play in providing support for patients. This article provides an overview of APL, including the epidemiology and pathophysiology that distinguishes APL from other types of acute leukemia. Clinical presentation and diagnostic workup for patients suspected of having APL will be reviewed, as will the treatment course. Nursing implications and management will be provided related to potential treatment complications specific to APL, including coagulopathies, differentiation syndrome, and QT prolongation with the use of arsenic trioxide, as will the side effects and complications that can occur in any patient with leukemia, such as infection, hyperleukocytosis, tumor lysis, and increased intracranial pressure.     

亚砷酸注射液治疗急性早幼粒细胞白血病副反应的观察与护理

目的探讨AS2O3治疗急性早幼粒细胞白血病(APL)的安全性.方法对36例用AS2O3治疗的APL患者的副反应进行了观察和护理.结果常见副反应中,白细胞过多综合征发生率为66.67%,胃肠道反应发生率为55.56%;皮肤指(趾)甲改变发生率为41.67%.性别、年龄及初治、复治因素对副反应发生无影响.结论加强对患者的观察,及时做好心理护理,对提高砷剂的疗效和安全性有重要意义.     

三氧化二砷联合沙利度胺治疗骨髓增生异常综合征的初步临床观察

目的初步观察三氧化二砷联合沙利度胺方案治疗骨髓增生异常综合征(MDS)的疗效及不良反应。方法共14例患者,7例给予三氧化二砷及反应停治疗,另7例仅给予对症处理及输血等支持治疗。结果接受治疗的7例患者中3例达PR,2例获得血液学改善。无严重不良反应。结论三氧化二砷联合沙利度胺是一种可选择的治疗MDS的方法,病人耐受性好。     

Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing

In the field of oncology, clinical molecular diagnostics and biomarker discoveries are constantly advancing as the intricate molecular mechanisms that transform a normal cell into an aberrant state in concert with the dysregulation of alternative complementary pathways are increasingly understood. Progress in biomarker technology, coupled with the companion clinical diagnostic laboratory tests, continue to advance this field, where individualized and customized treatment appropriate for each individual patient define the standard of care. Here, we discuss the current commonly used predictive pharmacogenetic biomarkers in clinical oncology molecular testing: BRAF V600E for vemurafenib in melanoma; EML4-ALK for crizotinib and EGFR for erlotinib and gefitinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; ERBB2 (HER2/neu) for trastuzumab in breast cancer; BCR-ABL for tyrosine kinase inhibitors in chronic myeloid leukemia; and PML/RARα for all-trans-retinoic acid and arsenic trioxide treatment for acute promyelocytic leukemia.     

三氧化二砷对急性早幼粒细胞白血病细胞凋亡相关基因表达的影响

本研究采用微矩阵基因芯片技术探讨三氧化二砷（As2O3）对NB4细胞凋亡的相关基因表达谱的影响。As2O3作用NB4细胞48小时，用改进的TRlzOL试剂一步法抽提As2O3作用前后的NB4细胞总RNA；经逆转录．聚合酶链反应后用Cy3标记的脱氧三磷酸尿苷（Cy32dUTP）和Cy52dUTP两种不同的荧光染料，将As2O3作用前后的NB4细胞mRNA分别标记成两种DNA探针，并与载有一组凋亡相关基因的表达谱芯片进行杂交，扫描分析筛选As2O3作用前后NB4细胞表达差异的凋亡基因；采用逆转录实时定量聚舍酶链反应（RQ—PCR）检测p2l，survivin，cdc2及WeelHu等方法检测细胞凋亡。结果表明：从As2O3作用后NB4细胞中筛选出表达差异的凋亡相关基因共18条，包括p21，survivin，cdc2及WeelHu等，表达上调的有6条，表达下调有12条；p21、survivin、cdc2及WeelHu可能与As20，诱导NB-4细胞的分化和（或）凋亡有关。结论：As203介导的NB4细胞凋亡的发生机制中、p21、sur-vivin、cdc2及Weel可能发挥着重要作用。