Myelodysplastic and myeloproliferative disorders of childhood
Myelodysplastic and myeloproliferative disorders of childhood
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DOI：
10.1182/asheducation-2016.1.598
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Hasle, Henrik
中科院分区：
文献类型：
--
作者：
Hasle, Henrik
骨髓增生异常综合征(MDS)和骨髓增生性疾病在儿童中很少见，分为低度MDS(儿童难治性红细胞减少[RCC])、晚期MDS(转化中原始细胞增多的难治性贫血)和幼年性粒单核细胞白血病(JMML)，每种疾病都有不同的特点和治疗策略。越来越多的患者认识到潜在的遗传易感性。生殖系GATA2突变在70%患有MDS和7号单体的青少年中被发现。肾癌与再生障碍性贫血、遗传性骨髓衰竭和反应性条件的区分是具有挑战性的。肾细胞癌通常是发育不良的，可能对免疫抑制治疗有反应。在免疫抑制治疗失败的情况下，高细胞性肾癌，或伴有单体7的肾癌，建议使用降低强度的预适应方案进行造血干细胞移植(HSCT)。几乎所有有原始细胞增多的难治性贫血患者都是HSCT的候选患者；12岁或12岁以上的儿童与治疗相关的死亡风险更高，因此应相应调整预适应方案。对JMML遗传学的研究表明，在具有胚系PTPN11和CBL突变的患者中，JMML往往会自发退化，很少有治疗的指征。相反，JMML和神经纤维瘤病1型、体细胞性PTPN11、KRAS和大多数NRAS突变的患者病情进展迅速，提示早期HSCT。移植后复发的风险很高，移植物抗宿主病的预防和监测应该适应这种风险。
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions. RCC is often hypoplastic and may respond to immunosuppressive therapy. In case of immunosuppressive therapy failure, hypercellular RCC, or RCC with monosomy 7, hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning regimens is indicated. Almost all patients with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatmentrelated death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL mutations often regresses spontaneously, and therapy is seldom indicated. Conversely, patients with JMML and neurofibromatosis type 1, somatic PTPN11, KRAS, and most of those with NRAS mutations have a rapidly progressive disease, and early HSCT is indicated. The risk of relapse after HSCT is high, and prophylaxis for graft-versus-host disease and monitoring should be adapted to this risk.