目的 探讨幼年型粒单核细胞白血病（juvenile myelomonocytic leukemia，JMML）的临床特征与预后之间的关系。 方法 收集2008年1月—2016年12月收治的JMML患儿临床资料及预后，分析影响JMML患儿预后的因素。 结果 共纳入63例JMML患儿，中位发病年龄为25个月，男女性别3.2∶1。54例患儿完成JMML基因检测，PTPN11基因突变最常见（23例，43%），其中单纯PTPN11基因突变19例，伴PTPN11基因复合突变4例；其次为NRAS基因突变（14例，26%），其中单纯NRAS基因突变12例，包含NRAS基因复合突变2例。5年总生存（overall survival，OS）率仅为22%±10%。13例（21%）患儿进行造血干细胞移植（hematopoietic stem cell transplantation，HSCT）。HSCT组患儿5年OS率高于非HSCT组患儿（46%±14% vs 29%±7%，P<0.05）。无PTPN11基因突变与PTPN11基因突变患儿5年OS率比较差异无统计学意义（30%±14% vs 27%±10%，P>0.05）。Cox比例风险回归模型分析显示，初诊血小板计数<40×109/L是影响JMML患儿5年OS率的因素（P<0.05）。 结论 PTPN11基因是JMML最常见的突变基因。初诊血小板计数与JMML患儿预后有关。HSCT可改善JMML患儿预后。
Abstract
Objective To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis. Methods Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed. Results A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05). Conclusions The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.
关键词
幼年型粒单核细胞白血病 /
基因突变 /
临床特征 /
预后 /
儿童
Key words
Juvenile myelomonocytic leukemia /
Gene mutation /
Clinical feature /
Prognosis /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
1 Chang TY, Dvorak CC, Loh ML. Bedside to bench in juvenile myelomonocytic leukemia: insights into leukemogenesis from a rare pediatric leukemia[J]. Blood, 2014, 124(16): 2487-2497. PMID: 25163700. DOI: 10.1182/blood-2014-03-300319.
2 Locatelli F, Algeri M, Merli P, et al. Novel approaches to diagnosis and treatment of juvenile myelomonocytic leukemia[J]. Expert Rev Hematol, 2018, 11(2): 129-143. PMID: 29279013. DOI: 10.1080/17474086.2018.1421937.
3 Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 127(20): 2391-2405. PMID: 27069254. DOI: 10.1182/blood-2016-03-643544.
4 Niemeyer CM, Flotho C. Juvenile myelomonocytic leukemia: who's the driver at the wheel?[J]. Blood, 2019, 133(10): 1060-1070. PMID: 30670449. DOI: 10.1182/blood-2018-11-844688.
5 Lasho T, Patnaik MM. Juvenile myelomonocytic leukemia—a bona fide RASopathy syndrome[J]. Best Pract Res Clin Haematol, 2020, 33(2): 101171. PMID: 32460983. DOI: 10.1016/j.beha.2020.101171.
6 Gupta AK, Meena JP, Chopra A, et al. Juvenile myelomonocytic leukemia—a comprehensive review and recent advances in management[J]. Am J Blood Res, 2021, 11(1): 1-21. PMID: 33796386. PMCID: PMC8010610.
7 Niemeyer CM. JMML genomics and decisions[J]. Hematology Am Soc Hematol Educ Program, 2018, 2018(1): 307-312. PMID: 30504325. PMCID: PMC6245977. DOI: 10.1182/asheducation-2018.1.307.
8 Locatelli F, Niemeyer CM. How I treat juvenile myelomonocytic leukemia[J]. Blood, 2015, 125(7): 1083-1090. PMID: 25564399. DOI: 10.1182/blood-2014-08-550483.
9 Meynier S, Rieux-Laucat F. After 95 years, it's time to eRASe JMML[J]. Blood Rev, 2020, 43: 100652. PMID: 31980238. DOI: 10.1016/j.blre.2020.100652.
10 Passmore SJ, Hann IM, Stiller CA, et al. Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system[J]. Blood, 1995, 85(7): 1742-1750. PMID: 7703482.
11 Murakami N, Okuno Y, Yoshida K, et al. Integrated molecular profiling of juvenile myelomonocytic leukemia[J]. Blood, 2018, 131(14): 1576-1586. PMID: 29437595. DOI: 10.1182/blood-2017-07-798157.
12 Fi?ana C, Gómez-Molina N, Alonso-Moreno S, et al. Genomic and epigenomic landscape of juvenile myelomonocytic leukemia[J]. Cancers (Basel), 2022, 14(5): 1335. PMID: 35267643. PMCID: PMC8909150. DOI: 10.3390/cancers14051335.
13 Dvorak CC, Satwani P, Stieglitz E, et al. Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: a Children's Oncology Group study[J]. Pediatr Blood Cancer, 2018, 65(7): e27034. PMID: 29528181. PMCID: PMC5980696. DOI: 10.1002/pbc.27034.
14 Nathany S, Chatterjee G, Ghai S, et al. Mutational landscape of juvenile myelomonocytic leukemia (JMML)—a real-world context[J]. Int J Lab Hematol, 2021, 43(6): 1531-1538. PMID: 34387930. DOI: 10.1111/ijlh.13680.
15 Mayerhofer C, Niemeyer CM, Flotho C. Current treatment of juvenile myelomonocytic leukemia[J]. J Clin Med, 2021, 10(14): 3084. PMID: 34300250. PMCID: PMC8305558. DOI: 10.3390/jcm10143084.
16 Marcu A, Colita A, Radu LE, et al. Single-center experience with epigenetic treatment for juvenile myelomonocytic leukemia[J]. Front Oncol, 2020, 10: 484. PMID: 32328464. PMCID: PMC7161089. DOI: 10.3389/fonc.2020.00484.
17 Lin YC, Luo CJ, Miao Y, et al. Human leukocyte antigen disparities reduce relapse after hematopoietic stem cell transplantation in children with juvenile myelomonocytic leukemia: a single-center retrospective study from China[J]. Pediatr Transplant, 2021, 25(2): e13825. PMID: 33131184. DOI: 10.1111/petr.13825.
18 Loh ML. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia[J]. Br J Haematol, 2011, 152(6): 677-687. PMID: 21623760. DOI: 10.1111/j.1365-2141.2010.08525.x.
19 Yoshida N, Doisaki S, Kojima S. Current management of juvenile myelomonocytic leukemia and the impact of RAS mutations[J]. Paediatr Drugs, 2012, 14(3): 157-163. PMID: 22480363. DOI: 10.2165/11631360-000000000-00000.
PDF(608 KB)
