达沙替尼治疗对急性髓系白血病儿童身高的影响

郑方圆, 陆爱东, 张乐萍, 左英熹, 贾月萍, 吴珺

中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (1) : 47-52.

PDF(1297 KB)
HTML
PDF(1297 KB)
HTML
中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (1) : 47-52. DOI: 10.7499/j.issn.1008-8830.2020.01.010
论著·临床研究

达沙替尼治疗对急性髓系白血病儿童身高的影响

  • 郑方圆, 陆爱东, 张乐萍, 左英熹, 贾月萍, 吴珺
作者信息 +

Influence of dasatinib treatment on body height in children with acute myeloid leukemia

  • ZHENG Fang-Yuan, LU Ai-Dong, ZHANG Le-Ping, ZUO Ying-Xi, JIA Yue-Ping, WU Jun
Author information +
文章历史 +

摘要

目的 探讨达沙替尼治疗对急性髓系白血病(AML)儿童身高的影响。方法 回顾性分析86例17岁以下AML儿童的临床资料,按照患儿的治疗方案分为常规化疗组和达沙替尼组:常规化疗组应用常规化疗药物而不使用酪氨酸激酶抑制剂,共57例;达沙替尼组应用常规化疗药物并加用达沙替尼治疗,共29例。对两组患儿在治疗开始时、治疗后的身高标准差积分(HtSDS)以及治疗后1年、治疗后2年HtSDS变化进行比较。结果 常规化疗组及达沙替尼组在治疗前HtSDS的比较差异无统计学意义(P > 0.05)。达沙替尼组在治疗前两年内HtSDS变化与常规化疗组保持一致。随访时达沙替尼组共有4人达到成年终身高,均显著低于遗传靶身高(P=0.044)。常规化疗组中成年终身高与遗传靶身高差异无统计学意义。达沙替尼组中青春期儿童治疗后与治疗前的HtSDS相比较差异有统计学意义(P=0.032)。结论 达沙替尼治疗可影响AML儿童的终身高,青春期开始后应用达沙替尼会存在生长障碍,但治疗短期内对身高影响不大。

Abstract

Objective To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML). Methods A retrospective analysis was performed for the clinical data of 86 AML children aged < 17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment. Results There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032). Conclusions Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.

关键词

达沙替尼 / 急性髓系白血病 / 身高 / 儿童

Key words

Dasatinib / Acute myeloid leukemia / Body height / Child

引用本文

导出引用
郑方圆, 陆爱东, 张乐萍, 左英熹, 贾月萍, 吴珺. 达沙替尼治疗对急性髓系白血病儿童身高的影响[J]. 中国当代儿科杂志. 2020, 22(1): 47-52 https://doi.org/10.7499/j.issn.1008-8830.2020.01.010
ZHENG Fang-Yuan, LU Ai-Dong, ZHANG Le-Ping, ZUO Ying-Xi, JIA Yue-Ping, WU Jun. Influence of dasatinib treatment on body height in children with acute myeloid leukemia[J]. Chinese Journal of Contemporary Pediatrics. 2020, 22(1): 47-52 https://doi.org/10.7499/j.issn.1008-8830.2020.01.010

参考文献

[1] García-Gutiérrez V, Hernández-Boluda JC. Tyrosine kinase inhibitors available for chronic myeloid leukemia:efficacy and safety[J]. Front Oncol, 2019, 9:603.
[2] Carpiuc KT, Rosti G, Castagnetti F, et al. Indirect comparisons of second-generation tyrosine kinase inhibitors in CML:case study using baseline population characteristics[J]. Onco Targets Ther, 2010, 3:205-210.
[3] Giona F, Mariani S, Gnessi L, et al. Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty[J]. Haematologica, 2013, 98(3):e25-e27.
[4] Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents[J]. Blood, 2019, 133(22):2374-2384.
[5] Millot F, Guilhot J, Baruchel A, et al. Growth deceleration in children treated with imatinib for chronic myeloid leukaemia[J]. Eur J Cancer, 2014, 50(18):3206-3211.
[6] Narayanan KR, Bansal D, Walia R, et al. Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis[J]. Pediatr Blood Cancer, 2013, 60(7):1148-1153.
[7] Ulmer A, Tabea Tauer J, Glauche I, et al. TK inhibitor treatment disrupts growth hormone axis:clinical observations in children with CML and experimental data from a juvenile animal model[J]. Klin Padiatr, 2013, 225(3):120-126.
[8] Bansal D, Shava U, Varma N, et al. Imatinib has adverse effect on growth in children with chronic myeloid leukemia[J]. Pediatr Blood Cancer, 2012, 59(3):481-484.
[9] Suttorp M, Yaniv I, Schultz KR. Controversies in the treatment of CML in children and adolescents:TKIs versus BMT?[J]. Biol Blood Marrow Transplant, 2011, 17(1 Suppl):S115-S122.
[10] Hobernicht SL, Schweiger B, Zeitler P, et al. Acquired growth hormone deficiency in a girl with chronic myelogenous leukemia treated with tyrosine kinase inhibitor therapy[J]. Pediatr Blood Cancer, 2011, 56(4):671-673.
[11] 吴雯. 酪氨酸激酶抑制剂治疗慢性髓系白血病临床随访研究[D]. 西安:第四军医大学, 2015.
[12] 中华医学会儿科学分会内分泌遗传代谢学组. 矮身材儿童诊治指南[J]. 中华医学信息导报, 2008, 23(24):20-21.
[13] 中华医学会儿科学分会血液学组, 中华儿科杂志编辑委员会. 儿童急性髓细胞白血病诊疗建议[J]. 中华儿科杂志, 2006, 44(11):877-878.
[14] Shima H, Tokuyama M, Tanizawa A, et al. Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia[J]. J Pediatr, 2011, 159(4):676-681.
[15] Krull KR, Li C, Phillips NS, et al. Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia[J]. Cancer, 2019, 125(10):1748-1755.
[16] Isfan F, Kanold J, Merlin E, et al. Growth hormone treatment impact on growth rate and final height of patients who received HSCT with TBI or/and cranial irradiation in childhood:a report from the French Leukaemia Long-Term Follow-Up Study (LEA)[J]. Bone Marrow Transplant, 2012, 47(5):684-693.
[17] Kebapcilar L, Bilgir O, Alacacioglu I, et al. Does imatinib mesylate therapy cause growth hormone deficiency?[J]. Med Princ Pract, 2009, 18(5):360-363.
[18] Gupta P, Rai A, Mukherjee KK, et al. Imatinib inhibits GH secretion from somatotropinomas[J]. Front Endocrinol (Lausanne), 2018, 9:453.
[19] Rastogi MV, Stork L, Druker B, et al. Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia[J]. Pediatr Blood Cancer, 2012, 59(5):840-845.
[20] Tauer JT, Hofbauer LC, Jung R, et al. Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats[J]. PLoS One, 2015, 10(6):e0131192.
[21] van den Heijkant S, Hoorweg-Nijman G, Huisman J, et al. Effects of growth hormone therapy on bone mass, metabolic balance, and well-being in young adult survivors of childhood acute lymphoblastic leukemia[J]. J Pediatr Hematol Oncol, 2011, 33(6):e231-e238.
[22] Alemán JO, Farooki A, Girotra M. Effects of tyrosine kinase inhibition on bone metabolism:untargeted consequences of targeted therapies[J]. Endocr Relat Cancer, 2014, 21(3):R247-R259.
[23] Jaeger BA, Tauer JT, Ulmer A, et al. Changes in bone metabolic parameters in children with chronic myeloid leukemia on imatinib treatment[J]. Med Sci Monit, 2012, 18(12):CR721-CR728.
[24] Samis J, Lee P, Zimmerman D, et al. Recognizing endocrinopathies associated with tyrosine kinase inhibitor therapy in children with chronic myelogenous leukemia[J]. Pediatr Blood Cancer, 2016, 63(8):1332-1338.
[25] Slayton WB, Schultz KR, Kairalla JA, et al. Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome-positive acute lymphoblastic leukemia:results of Children's Oncology Group Trial AALL0622[J]. J Clin Oncol, 2018, 36(22):2306-2314.
[26] Gore L, Kearns PR, de Martino ML, et al. Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase:results from a phase II trial[J]. J Clin Oncol, 2018, 36(13):1330-1338.
[27] Zwaan CM, Rizzari C, Mechinaud F, et al. Dasatinib in children and adolescents with relapsed or refractory leukemia:results of the CA180-018 phase I dose-escalation study of the innovative therapies for children with cancer consortium[J]. J Clin Oncol, 2013, 31(19):2460-2468.
[28] Nishi Y, Tanaka T. Growth hormone treatment and adverse events[J]. Pediatr Endocrinol Rev, 2017, 14(Suppl 1):235-239.
[29] Magid K, Chatterton RT, Ahamed FU, et al. Childhood ecology influences salivary testosterone, pubertal age and stature of Bangladeshi UK migrant men[J]. Nat Ecol Evol, 2018, 2(7):1146-1154.


PDF(1297 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/