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中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (01) : 67 -73. doi: 10.3877/cma.j.issn.1673-5250.2020.01.009

所属专题: 文献

论著

恶性实体瘤继发白血病患儿的诊疗及预后
张谊1, 张伟令1, 黄东生1,(), 王一卓1, 孟雪1   
  1. 1. 首都医科大学附属北京同仁医院儿科 100176
  • 收稿日期:2019-08-11 修回日期:2020-01-11 出版日期:2020-02-01
  • 通信作者: 黄东生

Diagnosis, treatment and prognosis of secondary leukemia in children with malignant solid tumor

Yi Zhang1, Weiling Zhang1, Dongsheng Huang1,(), Yizhuo Wang1, Xue Meng1   

  1. 1. Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing 100176, China
  • Received:2019-08-11 Revised:2020-01-11 Published:2020-02-01
  • Corresponding author: Dongsheng Huang
  • About author:
    Corresponding author: Huang Dongsheng, Email:
  • Supported by:
    Dengfeng Talent Project of Beijing Municipal Administration of Hospitals(DFL20180201); Beijing 215 Medical High Level Talents Backbone Project(2016-03-018)
引用本文:

张谊, 张伟令, 黄东生, 王一卓, 孟雪. 恶性实体瘤继发白血病患儿的诊疗及预后[J/OL]. 中华妇幼临床医学杂志(电子版), 2020, 16(01): 67-73.

Yi Zhang, Weiling Zhang, Dongsheng Huang, Yizhuo Wang, Xue Meng. Diagnosis, treatment and prognosis of secondary leukemia in children with malignant solid tumor[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(01): 67-73.

目的

探讨恶性实体瘤患儿放、化疗后,继发白血病的临床特点、类型、治疗及预后。

方法

选择北京同仁医院2007年5月至2017年5月,收治的2 269例恶性实体瘤患儿中,随访至2019年1月时,已经被确诊为继发白血病的3例患儿为研究对象。回顾性分析这3例患儿的临床病例资料,包括原发恶性实体瘤及继发白血病的临床特点、治疗及预后等。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求。对患儿的治疗,其家属均知情同意。

结果

①原发恶性实体瘤类型及其确诊时患儿年龄:3例患儿原发恶性实体瘤类型分别为腹膜后神经母细胞瘤(NB)4期(患儿1)、左眼眶横纹肌肉瘤(RMS)Ⅲ期(患儿2)、左眼视网膜母细胞瘤(RB)眼外期(患儿3),均为男性患儿;其确诊时年龄分别为2岁1个月、8岁和3岁。②原发恶性实体瘤的治疗方案及疗效:对患儿1化疗29个周期结合手术、自体外周血造血干细胞移植(HSCT)后,达到非常好部分缓解(VGPR);对患儿2化疗12个周期结合手术及眼眶区放疗后,达到完全缓解(CR);对患儿3化疗14个周期及手术后,达到CR。③恶性实体瘤化疗药物应用特点:3例患儿采用的化疗药物均包括长春新碱及依托泊苷,应用周期最长分别为,NB患儿采用长春新碱15个周期及RB患儿采用依托泊苷14个周期。应用铂类药物最长周期为,RB患儿采用卡铂14个周期,NB患儿采用顺铂8个周期。④继发白血病的诊治及预后:NB、RMS及RB患儿继发白血病的时间,距离原发肿瘤停止放化疗的时间分别为6、25、10个月;白血病分型:NB、RMS患儿均为急性髓细胞白血病(AML)(M2型),RB患儿则为急性B淋巴细胞白血病(B-ALL)(L2型)。针对继发白血病治疗后,NB及RMS患儿于继发白血病确诊后的12、5个月死亡;RB患儿经化疗及半相合异基因HSCT后,白血病达到CR,获得无病生存。

结论

长期化疗,可能为恶性实体瘤患儿发生继发白血病的主要原因。恶性实体瘤患儿化疗后,应针对白血病相关检查指标进行监测,以达到对其继发白血病的早诊断、早治疗目的。

Objective

To explore the clinical characteristics, types, treatment and prognosis of secondary leukemia due to chemotherapy and radiotherapy in children with malignant solid tumor.

Methods

Followed up to January 2019, we confirmed 3 children with secondary leukemia from 2 269 cases of malignant solid tumor children who were diagnosed and treated from May 2007 to May 2017 in Beijing Tongren Hospital, and they were chosen as research subjects. The clinical data of 3 children including clinical characteristics, treatment and prognosis of primary malignant solid tumors and secondary leukemia were analyzed retrospectively. This study was in line with World Medical Association Declaration of Helsinki revised in 2013. For the treatment of the children, their families had informed consents.

Results

① Types of primary malignant solid tumors and diagnosis age of children: Primary malignant solid tumors of 3 children were 4 stage of neuroblastoma (NB)(patient 1), Ⅲ stage of left orbit rhabdomyosarcoma (RMS)(patient 2) and extraocular stage of left retinoblastoma (RB)(patient 3). All of male and the diagnosis age of primary diseases of children were 2 years and 1 month, 8 years and 3 years old. ② The therapy regimen of primary malignant solid tumor and curative effect: Patient 1 was treated with 29 cycles of chemotherapy, surgery and autologous peripheral blood hematopoietic stem cell transplantation (HSCT), and received very good partial remission (VGPR). Patient 2 was treated with 12 cycles of chemotherapy, surgery and radiotherapy, and received complete remission (CR). Patient 3 was treated with 14 cycles of chemotherapy and surgery, and received CR. ③ Characteristics of chemotherapy drugs for malignant solid tumors: ALL of 3 children received chemotherapy drugs with vincristine and etoposide. The longest application periods were NB child received 15 cycles of vincristine and RB child received 14 cycles of etoposide. The longest application periods of platinum drugs were RB child received 14 cycles of carboplatin and NB child received 8 cycles of cisplatin. ④ Diagnosis, treatment and prognosis of secondary leukemia: The onset time of secondary leukemia to chemotherapy stop time of primary tumor of NB, RMS and RB children were 6, 25 and 10 months, respectively. The clinical leukemia types were NB and RMS children with acute myeloid leukemia (AML, M2 type) and RB child with acute B-lymphocytic leukemia (B-ALL, L2 type) . After chemotherapy for secondary leukemia, children with NB and RMS were dead 12 and 5 months after diagnosis of AML, respectively. The RB child with B-ALL achieved CR and free event survival after chemotherapy and haploidentical allogeneic HSCT.

Conclusions

Long period of chemotherapy for malignant solid tumor might be a main reason of resulting in secondary leukemia. Therefore, the monitoring of leukemia related examinations should be taken after malignant solid tumor chemotherapy, to achieve early diagnosis and treatment for secondary leukemia.

表1 3种恶性实体瘤化疗方案及造血干细胞移植预处理方案
病种 化疗方案 剂量 用法
NB CDV(环磷酰胺+多柔比星+长春新碱) 环磷酰胺(cyclophosphamide):2.1 g/(m2·d) 持续静脉滴注48 h
? ? 多柔比星(doxorubicin):25 mg/(m2·d) 持续静脉滴注72 h
? ? 长春新碱(vincristine):1.5 mg/(m2·d) 持续静脉滴注72 h
? CiE(顺铂+依托泊苷) 顺铂(cisplatin):50 mg/(m2·d) 静脉滴注d1~4
? ? 依托泊苷(etoposide):200 mg/(m2·d) 静脉滴注d1~3
? TC(托泊替康+环磷酰胺) 托泊替康(topotecan):1.2 mg/(m2·d) 静脉滴注d1~5
? ? 环磷酰胺(cyclophosphamide):250 mg/(m2·d) 静脉滴注d1~5
? CEM(卡铂+依托泊苷+美法仑) 卡铂(carboplatin):300 mg/(m2·d) 静脉滴注d-7~-4
? ? 依托泊苷(etoposide):200 mg/(m2·d) 静脉滴注d-7~-4
? ? 美法仑(melphalan):70 mg/(m2·d) 静脉滴注d-7~-5
RMS AVCP(多柔比星+长春新碱+环磷酰胺+顺铂) 多柔比星(doxorubicin):25 mg/(m2·d) 静脉滴注d2、9
? 长春新碱(vincristine):1.5 mg/(m2·d) 静脉滴注d1、8
? ? 环磷酰胺(cyclophosphamide):1.2 g/(m2·d) 静脉滴注d2~4
? ? 顺铂(cisplatin):90 mg/(m2·d) 静脉滴注d3
? IEV(异环磷酰胺+依托泊苷+长春新碱) 异环磷酰胺(ifosfamide):1.5 g/(m2·d) 静脉滴注d2~4
? ? 依托泊苷(etoposide):200 mg/(m2·d) 静脉滴注d1~3
? ? 长春新碱(vincristine):1.5 mg/(m2·d) 静脉滴注d1、8
RB CEV(卡铂+依托泊苷+长春新碱) 卡铂(carboplatin):200 mg/(m2·d) 静脉滴注d1~3
? ? 依托泊苷(etoposide):100 mg/(m2·d) 静脉滴注d1~3
? ? 长春新碱(vincristine):1.5 mg/(m2·d) 静脉滴注d1
表2 3例恶性实体瘤患儿初诊时一般临床资料
表3 3例恶性实体瘤患儿常规化疗药物总剂量及使用周期
表4 3例继发白血病患儿白血病相关临床资料
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