儿童急性早幼粒细胞白血病临床特点和预后分析

儿童急性早幼粒细胞性白血病（acute prom yetocytic leukemia,APL）的发病率约为儿童急性髓细胞性白血病（acute myeloid leukemia,AML）的10%,其高白细胞的发生率很高,PML/PARα融合基因常见。临床上,该病患儿往往具有严重出血倾向,甚至发生颅内出血、弥散性血管内凝血（DIC）而危及生命。全反式维甲酸（ATRA）及三氧化二砷（AS2O3）的出现极大改变了APL的治疗效果,使其成为各种ANLL中治疗效果相对较好的一种。目前全反式维甲酸联合化疗能治愈至少70%～75%的初诊APL。     

急性早幼粒细胞白血病治疗进展

急性早幼粒细胞白血病(APL)占儿童AML0%,具有和成人APL相同的临床表现、细胞形态学、遗传学和分子生物学特征。约95%患者携带t(15;17)染色体易位,白血病细胞分化阻滞在早幼粒细胞阶段,临床出血征明显,常伴弥散性血管内凝血(DIC),肝脾淋巴结肿大少见。免疫分型CD9、CD13、CD33阳性,而CD34、HLA-DR阴性。由于儿童APL病例数相对较少,因此目前儿童APL都采用与成人APL相同的治疗方案,本文分析综述近年来APL治疗进展,期望对儿童APL的治疗有借鉴和指导作用。诱导缓解治疗由于全反式维甲酸(ATRA)靶向治疗的基础是APL t(15;17)形…     

急性早幼粒细胞性白血病端粒酶活性变化及其临床意义

目的 寻求新的肿瘤监测指标，探索端粒酶活性在急性早幼粒细胞性白血病化疗过程中的动态变化，并评判酶活性与预后的相关性。方法 用TRAP Elisa PCR方法对照研究10例早幼粒白血病患者起病初及经全反式维甲酸等治疗诱导缓解后的端粒酶活性，并比较肿瘤负荷、年龄、治疗措施及缓解时间对端粒酶活性的影响。结果 与正常同龄者相比，白血病患者骨髓细胞具有明显增高的端粒酶活性；经治疗缓解后，患者的端粒酶活性明显下降并几乎恢复正常；1例缓解后端粒酶活性仍较明显升高者，疾病很快复发；单纯维甲酸治疗与维甲酸结合化疗者达到缓解时端粒酶活性无明显差异；不同年龄、不同时间达到诱导缓解者端粒酶活性也无明显差异。结论 端粒酶活性是急性早幼粒细胞性白血病细胞的普遍标记，酶活性强度与肿瘤负荷明显相关，端粒酶活性有可能成为监测残留肿瘤细胞、评价治疗效果、预测肿瘤预后的指标。     

维甲酸治疗儿童急性早幼粒细胞白血病5例临床报告

本文报道单用维甲政治疗5例小儿急性早幼粒细胞白血病,均获完全缓解,剂量为60～100mg/m~2/d。体外骨髓细胞培养中维甲酸能明显诱导早幼粒白血病细胞的形态和功能成熟,因此是诱导急性早幼粒细胞白血病达到完全缓解的有效药物。     

“713”注射液可长期缓解儿童复发性早幼粒细胞型白血病──附2例报告

急性早幼粒细胞白血病（APL）在儿童白血病中发病率较低，但其病情与成人一样比较凶险，死亡率较高。按传统的治疗方法使用细胞毒药物（化疗）杀伤白血病细胞，易导致严重出血，造成死亡。86年以来，我国采用全反式维甲酸（ATRA）诱导分化治疗该病以来，其完全缓解率（CR）明显提高。但是A－TRA不能单独用于维持治疗，经研究发现，APL经ATRA治疗缓解后，若继续使用则极易早期复发，再用ATRA往往失效。虽然加用化疗方法可使复发病例的缓解率略有升高，但效果也不尽人意。我们用"713"注射液治疗了2例复发性的早幼粒细胞性白血病（"7…     

儿童急性早幼粒细胞性白血病并发DIC的临床研究

目的 回顾性分析26例急性早幼粒细胞性白血病(APL)患儿合并DIC的发生率、临床特点及预后情况.方法 26例初诊APL患儿以骨髓形态学及免疫学分型确诊.应用三氧化二砷(As2O3)进行诱导缓解,监测血常规及DIC指标.结果 23例患儿发生DIC(88%),诊断时即发生DIC 12例(52%),As2O3治疗2周内发生DIC 9例(39%),2周后发生DIC 2例(9%).DIC出血19例(73%),以皮肤出血9例(47%)为著,颅内出血2例(11%)均死亡.DIC指标以血小板下降最为敏感(100%),凝血酶原时间及部分凝血酶原时间延长者22例(96%),也有较高敏感性.DIC指标转阴需4～46d.结论 儿童APL合并DIC发生率较高,出血风险大,以诊断及治疗2周内为危险期,需积极监测DIC指标,在治疗APL基础上抗DIC治疗,以度过DIC期,保证诱导缓解期治疗的安全性.     

肿瘤

051280急性早幼粒细胞性白血病端粒酶活性变化及其临床意义/陈静…∥临床儿科杂志.-2004,22(2).-76～78用TRAPElisaPCR方法对照研究10例早幼粒白血病患者起病初及经全反式维甲酸等治疗诱导缓解后的端粒酶活性,并比较肿瘤负荷、年龄,治疗措施及缓解时间对端粒酶活性的影响。观察经治疗缓解后端粒酶活性的变化。结果表明,端粒酶活性是急性早幼粒细胞白血病细胞的普遍标记,酶活性强度与肿瘤负荷明显相关,端粒酶活性有可能成为监测残留肿瘤细胞,评价治疗效果,预测肿瘤预后的指标。表1参12(何燕)051281大剂量甲氨蝶呤预防标危型儿童急性淋巴…     

全反式维甲酸治疗小儿急性早幼粒细胞性白血病(附9例报告)

急性早幼粒细胞性白血病(APL)发病急,病情重,易出血并易发生DIC,单用化疗效果欠佳。近年来应用诱导分化剂治疗取得满意效果。现将我们应用全反式维甲酸治疗9例小儿APL报告如下,临床资料一、一般资料:男性3例,女性6例。年龄均在5～12岁内。二、临床表现:9例病人均有不同程度的出血,表现为皮肤淤点、淤斑、鼻衄、齿龈出血和便血,大     

儿童急性淋巴细胞白血病诱导化疗前凝血指标改变意义探讨

目的分析儿童急性淋巴细胞白血病诱导化疗前凝血指标改变及相关因素,指导治疗、减少并发症发生。方法检测北京儿童医院血液病中心一病房2004年收治的初发急性淋巴细胞白血病63例病人的诱导化疗前凝血指标、免疫分型、临床指标及诱导治疗早期(2周内)并发症,分析它们之间关系。结果有30例(47.6%)病人化疗前有凝血指标改变:1、与临床出血表现、血小板减少无明显关系(P>0.05),2、与白细胞增多、肾脏浸润、谷草转氨酶/尿酸升高无明显关系(P>0.05)、与组织肿瘤负荷大、乳酸脱氢酶上升有明显关系(P<0.05);与免疫分型T细胞型有明显关系;与危险度无明显关系(P>0.05)。3、诱导化疗前凝血指标异常与诱导化疗2周内出现的与DIC发生倾向有明显关系(P<0.01),与高尿酸血症、肾功能不全无明显关系(P>0.05)。结论儿童急性淋巴细胞白血病诱导化疗前可有凝血指标改变,1、临床出血表现、血小板数量并不能反映、替代凝血指标改变,2、发生凝血指标改变的高危因素可能有高肿瘤负荷、高LDH、T细胞型白血病,3、凝血指标的改变提示了诱导化疗2周内DIC发生的可能性。因此要重视其变化,积极纠正,是减少临床相关并发症的有效方法。     

儿童急性非淋巴细胞白血病疗效观察：附31例分析

本文总结了３１例儿童急性非淋巴细胞白血病的疗效：Ｍ３组１３例，均予全反式维甲酸诱导分化缓解，再予ＡＴＲＡ及化疗交替维持强治疗。     

All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia

All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.     

Use of all-trans retinoic acid to treat acute promyelocytic leukemia: A case with very severe features at the onset in Nicaragua

We observed a child with acute promyelocytic leukemia (APL) who, at the onset, had extremely severe hemorrhagic and septic complications. According to our experience in Nicaragua, there was a very high risk of early death. The patient was successfully treated with a program that included all-trans retinoic acid (ATRA) followed by cytotoxic chemotherapy. ATRA has two important features: it is effective in initial treatment of APL and it is inexpensive. Because of the high cost and the need for extensive supportive care, optimal myeloablative therapy used in patients with various types of acute myeloid leukemia generally cannot be given in developing countries. ATRA treatment for APL is affordable everywhere. © 1996 Wiley-Liss, Inc.     

Effect of dialysis on all trans retinoic acid levels in a child with acute promyelocytic leukemia and renal failure

All trans retinoic acid (ATRA) combined with chemotherapy has become the mainstay of treatment for patients with acute promyelocytic leukemia (APL). Renal dysfunction (RD) is commonly seen in patients with APL. We describe a patient with APL and multi-organ failure, who was on chronic veno-venous hemofiltration followed by hemodialysis (HD) and later peritoneal dialysis (PD), who received ATRA. ATRA levels were assessed as the body clearance of ATRA in children on HD and/or PD was unknown. Neither HD nor PD significantly affected ATRA levels, suggesting that dose modifications of ATRA may not be necessary for children with these forms of renal replacement therapy.     

Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid

In this study, we show that all-trans retinoic acid (ATRA) treatment leads to a rapid decrease in telomerase activity, which was associated with the reduction in myeloblasts and occurs before the appearance of myelocytes, in a patient with acute promyelocytic leukemia (APL). Microarray analysis by ATRA treatment for 48 hr in peripheral blood mononuclear cells (in vivo) and in cultured bone marrow mononuclear cells (in vitro) from a patient with APL revealed upregulation of CD11b, CD11c, CCAAT enhancer binding protein epsilon, Rb1, Mad, and tumor necrosis factor-related genes; and downregulation of hTERT, c-Myc, WT1, bcl-2, and eukaryotic translation elongation factor 1alpha2. The results might offer the potential to define the molecular mechanism underlying ATRA-induced granulocytic differentiation in patients with APL, and provide clues to identify novel molecular therapeutic targets.     

Successful treatment of retinoic acid syndrome with high-dose dexamethasone pulse therapy in a child with acute promyelocytic leukemia treated with ATRA

A 5 year old female developed femoral pain, fever, and hemorrhagic tendency. She was diagnosed as having acute promyelocytic leukemia (APL). Approximately 2 weeks after the administration of all-trans retinoic acid (ATRA), she developed a high fever, edema, and respiratory distress which met the criteria for retinoic acid syndrome. At first, we tried to treat the patient with oral corticosteroid, however, this approach was unsuccessful. Considering the worsening of her condition, we then chose to administer a large dose of intravenous dexamethasone therapy for 3 days. Immediately after this therapy, she became afebrile, respiratory distress and edema disappeared, and there was a general improvement of the symptoms. All-trans retinoic acid at the reduced dose of 25 mg/m², was continued for an additional 6 weeks and then discontinued. Since the cessation of dexamethasone and ATRA, there has been no relapse of APL in this patient. Although based on only one case, we recommend the intravenous high-dose dexamethasone pulse therapy (13 mg/m² per day, for 3 days) for treating retinoic acid syndrome which develops in pediatric APL patients treated with ATRA.     

儿童急性早幼粒细胞白血病76例随访报告

目的 探讨儿童急性早幼粒细胞白血病(APL)的治疗及预后,并评估砷剂在儿童APL中的疗效.方法 对76例初治APL患儿进行疗效及预后相关因素分析.采用SPSS10.0软件进行统计学分析.结果 本组76例APL患儿,6例早期死亡.其余70例患儿依据诱导方案的不同分成3组:1组44例,单用全反式维甲酸(ATRA);2组7例,单用三氧化二砷(As_2O_3);3组19例,联合应用ATRA和As_2O_3.1组的完全缓解率为100%,2组+3组的完全缓解率为100%.6例临床复发,2例分子生物学复发,复发部位均为骨髓.5年累计复发率为13.8%,5年累积无事件生存(EFS)率、无病生存(DFS)率、总生存(OS)率分别为79.5%、86.3%和90.5%.在1组与2组+3组之间的5年EFS、DFS没有明显差异.初诊时白细胞计数可能是影响儿童预后最主要的因素.结论 ATRA治疗儿童APL疗效好.砷剂治疗儿童APL的疗效亦较好,耐受性好.砷剂可以用于不能耐受ATRA副作用的患儿,亦可用于初治和复发的儿童APL.     

Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia

All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.     

GENITAL ULCERS AFTER TREATMENT WITH ALL-trans-RETINOIC ACID IN A CHILD WITH ACUTE PROMYELOCYTIC LEUKEMIA

All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.     

儿童急性早幼粒细胞白血病PML-RARα融合基因跟踪检测的临床意义(英文)

目的　探讨跟踪检测急性早幼粒细胞白血病 (APL)特有的PML RARα融合基因在发现APL早期复发和指导APL临床治疗方面的意义。方法　 1 0例APL患儿用全反式维甲酸 (ATRA)和 (或 )其它化疗药物进行诱导缓解、巩固治疗和维持治疗 ,并进行随访。在病程的不同阶段采集骨髓标本进行形态学检查 ,并应用RT PCR方法检测PML RARα融合基因。结果　随访时间为 1 4～ 1 5 6月 (中位时间 4 2月 ) ,5年无病生存率为 5 6 .0 %±1 6 .5 %。 1 0例APL患儿完全缓解 (CR)率为 90 % ,早期死亡 1例。 9例CR病人中 4例在CR后 1 4～ 4 2月复发 ,4例在连续完全缓解 4～ 5年后已停药 ,停止治疗时间为 1 8～ 96月。 1例CR ,仍在继续治疗中。 9例CR患儿中 ,8例在病程中PML RARα转为阴性 ,1例持续阳性。 4例复发病人中 ,2例复发前持续阳性 ,2例在病程中由阴性转为阳性。 5例仍生存的患儿中 ,1例在病程中PML RARα由阴性转为阳性 ,2例分别在持续完全缓解 36和 4 2月仍呈阳性 ,这 3例患儿经治疗干预后均转阴 ,且长期生存。结论　对APL患儿跟踪检测PML RARα可早期发现分子复发 ,及时干预治疗可避免血液学复发。