不同方案诱导治疗儿童急性早幼粒细胞白血病的临床分析

摘要/Abstract

摘要：

　目的　比较全反式维甲酸（ATRA）和三氧化二砷（As₂O₃）联合与不联合蒽环类药物诱导治疗儿童急性早幼粒细胞白血病（APL）的疗效和不良反应。方法　回顾性分析2002 年1月1日至2012 年12月31日初治的46例APL患儿的临床资料，并根据不同诱导化疗方案和初始白细胞高低进行分组和对比分析。结果　30例不加蒽环组患儿中有2例早期死亡，而 16例加蒽环组患儿无1例早期死亡。加蒽环组与不加蒽环组的完全缓解率、达分子学缓解时间和诱导化疗结束时微小残留病定量分析的差异均无统计学意义（P>0.05）。加蒽环组的高白细胞持续时间明显短于不加蒽环组，差异有统计学意义（P<0.05）。33例低白细胞患儿中，11例加蒽环组患儿的白细胞峰值低于22例不加蒽环组，差异有统计学意义（P<0.05）。全体加蒽环组和不加蒽环组的凝血异常时间、肝脏毒性、感染率差异无统计学意义（P均>0.05）。结论　儿童APL诱导化疗中联合蒽环类药物可减少高白细胞持续时间，降低白细胞峰值，有助于减少早期死亡。

Abstract: 　Objectives　To compare the efficacy and adverse effects of combining all-trans retinoic acid and arsenic trioxide with or without anthracyclines on the treatment of childhood acute promyelocytic leukemia (APL) patients. Methods The retrospective study included 46 children as newly diagnosed APL from January 1st, 2001 to December 31st , 2012. Efficacy and adverse effects for different induction therapies and in high and low white blood cell (WBC) count subgroups were studied. Results In the non antharcycline containing group, 2 patients died during remission induction, and in the antharcycline containing group none of the patients died. No statistical difference was observed between the antharcycline containing group and the non antharcycline containing group in complete remission, the length of time to achieve molecular complete remission and minimal residual disease quantitative analysis at the end of the induction.The mean duration of high WBC count subgroup in the antharcycline containing group was shortened than that of the non antharcycline containing group (P＜0.05). In the low WBC subgroups, the WBC count peak in the antharcycline containing group was lower than that of the non antharcycline containing group (P＜0.05); The recovery time of the abnormal coagulation was found similar between these two groups. Conclusions The use of antharcycline in induction therapy could shorten the duration of high WBC count and reduced the WBC count peak , thus reduces the risk of early death.

王静，贾月萍，刘桂兰，陆爱东，张乐萍，左英熹，王彬. 不同方案诱导治疗儿童急性早幼粒细胞白血病的临床分析[J]. 临床儿科杂志, 2014, 32(5): 405-409.

WANG Jing,JIA Yueping,LIU Guilan,LU Aidong,ZHANG Leping,ZUO Yingxi,WANG Bin. Different induction therapies in the treatment of childhood acute promyelocytic leukemia　[J]. , 2014, 32(5): 405-409.

参考文献

[1] Shen ZX，Shi ZZ，Fang J，et al. All-trans retinoic acid/As₂O₃ combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia [J]. Proc Natl Acad Sci U S A，2004，101(15)：5328-5335.
[2] Iland HJ，Bradstock K，Supple SG，et al. All-trans-retinoic acid，idarubicin，and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4) [J]. Blood，2012，120(8)：1570-1580，1752..
[3] Dai CW，Zhang GS，Shen JK，et al. Use of all-trans retinoic acid in combination with arsenic trioxide for remission induction in patients with newly diagnosed acute promyelocytic leukemia and for consolidation/maintenance in CR patients [J]. Acta Haematol，2009，121(1)：1-8.
[4] Fenaux P，Chastang C，Chevret S，et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group [J]. Blood，1999，94(4)：1192-1200.
[5] 张之南，沈悌. 血液病诊断及疗效标准 [M]. 3版. 北京：北京科学技术出版社，2007：106-133.
[6] Fenaux P，Le Deley DM，Castaigne S，et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group [J]. Blood，1993，82(11)：3241-3249.
[7] Breen KA，Grimwade D，Hunt BJ. The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia [J]. Br J Haematol，2012，156(1)：24-36.
[8] Campos L，Guyotat D，Archimbaud E，et al. Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis [J]. Blood，1992，79(2)：473-476.
[9] 王冠军，李薇，崔久嵬，等. 三氧化二砷联合小剂量全反式维甲酸诱导急性早幼粒细胞白血病缓解的疗效分析 [J]. 中国医学杂志，2005，85(16)：1093-1096.
[10] Ravandi F，Estey E，Jones D，et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid，arsenic trioxide，and gemtuzumab ozogamicin [J]. J Clin Oncol，2009，27(4)：504-510.
[11] 刘元昉，沈志祥，陈晓，等. 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观察 [J]. 中华血液学杂志，2003，24(1)：25-27.
[12] 赵耀中，李洪强，李大鹏，等. 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初步观察 [J]. 中华血液学杂志，2003，24(1)：32-34.
[13] de Botton S，Chevret S，Coiteux V，et al. Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts：results from APL 93 trial [J]. Leukemia，2003，17(2)：339-342.
[14] 郭为民，诸江，王鸿利，等. 维甲酸、砷剂及柔红霉素对NB4细胞组织因子表达的影响 [J]. 中华血液学杂志，1999，20(9)：453-455.
[15] 史家岚，李金梅，侯金晓，等. 三氧化二砷和柔红霉素对急性早幼粒细胞白血病细胞的促凝血活性的影响 [J]. 中华医学杂志，2012， 92(16)：1095-1099.
[16] 胡炯，沈志祥，仇倩瑶，等. 急性早幼粒细胞白血病纤溶异常研究 [J]. 中华血液学杂志，1997，18(1)：45-46.
[17] Falanga A，Iacoviello L，Evangelista V，et al. Loss of blast cell procoagulant activity and improvement of hemostatic variables in patients with acute promyelocytic leukemia administered all-trans-retinoic acid [J]. Blood，1995，86(3)：1072-1081.
[18] de la Serna J，Montesinos P，Vellenga E，et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-transretinoic acid and idarubicin [J]. Blood，2008，111(7)：3395-3402.