阿糖胞苷在全反式维甲酸和三氧化二砷联合治疗儿童急性早幼粒细胞白血病中的作用：一项随机对照试验。
Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial.
机构信息
State Key Laboratory of Experimental Hematology, Department of Paediatrics Haematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
出版信息
BMC Cancer. 2018 Apr 3;18(1):374. doi: 10.1186/s12885-018-4280-2.
BACKGROUND
The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children.
METHODS
We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016. All of the patients were assigned to receive ATRA plus ATO for induction followed by one course of idarubicin (IDA) and ATO (28 days). The patients were then randomly assigned to receive two courses of daunorubicin (DNR, no- Ara-C group) or DNR + Ara-C (Ara-C group). All of the patients were followed with maintenance therapy with oral ATRA, 6-mercaptopurine, and methotrexate for 1.5 years.
RESULTS
Among the 66 patients, 43 were male and 23 were female. All of the patients achieved complete remission (CR) with the exception of one who gave up the treatment. During induction therapy, all toxicity events were reversed after appropriate management. Thirty patients in the Ara-C group underwent 57 courses of treatment, and 35 patients in the no-Ara-C group underwent 73 courses of treatment. No significant differences in age, genders, white blood cell counts, haemoglobin levels, and platelet counts were found between the Ara-C and no-Ara-c groups. Greater myelosuppression and sepsis were observed in the Ara-C group during the consolidation courses. No patient died at consolidation, and only one patient relapsed. No differences were found in event-free survival, disease-free survival and overall survival between the two groups. Additionally, our analysis of the arsenic levels in the plasma, urine, hair and nails of the patients indicated that no significant accumulation of arsenic occurred after ATO was discontinued for 12 months.
CONCLUSIONS
Overall, ATO and ATRA are safe and effective for paediatric APL patients and Ara-C could be omitted when ATO is used for two courses.
TRIAL REGISTRATION
ClinicalTrials.gov ( NCT01191541 , retrospectively registered on 18 August 2010).
背景
全反式维甲酸（ATRA）和三氧化二砷（ATO）的联合应用已被证明对成人急性早幼粒细胞白血病（APL）是安全有效的。截至 2010 年，阿糖胞苷（Ara-C）在 APL 中的作用仍存在争议。本研究旨在检验 ATRA 和 ATO 对儿科 APL 患者的疗效和安全性。此外，我们还评估了在儿童 ATO 和 ATRA 为基础的试验中是否可以省略 Ara-C。
方法
我们于 2010 年 5 月至 2016 年 12 月在我院进行了一项儿科 APL 患者（≤14 岁）的随机对照试验。所有患者均接受 ATRA 加 ATO 诱导治疗，随后接受一个疗程的伊达比星（IDA）和 ATO（28 天）。然后，患者随机分为接受两个疗程的柔红霉素（DNR，无 Ara-C 组）或 DNR+Ara-C（Ara-C 组）。所有患者均接受维持治疗，口服 ATRA、6-巯基嘌呤和甲氨蝶呤 1.5 年。
结果
在 66 例患者中，男性 43 例，女性 23 例。除 1 例患者放弃治疗外，其余患者均达到完全缓解（CR）。在诱导治疗期间，所有毒性反应均经适当处理后得到逆转。Ara-C 组有 30 例患者接受 57 个疗程治疗，无 Ara-C 组有 35 例患者接受 73 个疗程治疗。Ara-C 组和无 Ara-C 组在年龄、性别、白细胞计数、血红蛋白水平和血小板计数方面无显著差异。在巩固治疗期间，Ara-C 组患者骨髓抑制和脓毒症更为严重。在巩固治疗期间，没有患者死亡，只有 1 例患者复发。两组患者无事件生存、无病生存和总生存无差异。此外，我们对患者血浆、尿液、毛发和指甲中的砷水平进行的分析表明，ATO 停药 12 个月后，砷无明显蓄积。
结论
总的来说，ATO 和 ATRA 对儿科 APL 患者安全有效，当 ATO 用于两个疗程时，可省略 Ara-C。
试验注册
ClinicalTrials.gov（NCT01191541，2010 年 8 月 18 日回顾性注册）。
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