文章：

幼年型粒单核细胞白血病与努南综合征相关骨髓增殖性疾病的观察与管理：一项真实世界经验

Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience

原文发布日期：2 August 2024

DOI: 10.3390/cancers16152749

类型: Article

开放获取: 是

英文摘要：

Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The aim of our retrospective review is to describe the treatment and outcomes of a cohort of patients with JMML or Noonan Syndrome-associated Myeloproliferative Disorder (NS-MPD) to provide management guidance for this rare and heterogeneous disease. We report on 22 patients with JMML or NS-MPD managed at three institutions in the Texas Medical Center. Of patients with known genetic mutations and cytogenetics, 6 harbored germline mutations, 12 had somatic mutations, and 9 showed cytogenetic abnormalities. Overall, 14/22 patients are alive. Spontaneous clinical remission occurred in one patient with somaticNRASmutation, as well as two with germlinePTPN11mutations with NS-MPD, and two others with germlinePTPN11mutations and NS-MPD remain under surveillance. Patients with NS-MPD were excluded from treatment analysis as none required chemotherapeutic intervention. All patients (5/5) treated with 5-azacitidine alone and one of the four treated with 6-mercaptopurine monotherapy had a reduction in mutant variant allele frequency. Transformation to acute myeloid leukemia was seen in two patients who both died. Among patients who received transplants, 7/13 are alive, and relapse post-transplant occurred in 3/13 with a median time to relapse of 3.55 months. This report provides insight into therapy responses and long-term outcomes across different genetic subsets of JMML and lends insight into the expected time to spontaneous resolution in patients with NS-MPD with germlinePTPN11mutations.

摘要翻译： 

幼年型粒单核细胞白血病（JMML）是一种罕见的克隆性婴幼儿期造血系统疾病，具有骨髓增殖性/骨髓增生异常特征，由RAS信号通路胚系或体细胞突变引起。其治疗方案尚未统一，临床处理策略可从观察等待延伸至干细胞移植。本回顾性研究旨在描述一组JMML或努南综合征相关骨髓增殖性疾病（NS-MPD）患者的治疗及预后，为这类罕见异质性疾病提供诊疗指导。我们报道了在德克萨斯医学中心三家机构接受治疗的22例JMML或NS-MPD患者。在已知基因突变和细胞遗传学特征的患者中，6例携带胚系突变，12例存在体细胞突变，9例显示细胞遗传学异常。总体生存率为14/22。1例体细胞NRAS突变患者及2例携带胚系PTPN11突变的NS-MPD患者出现自发临床缓解，另有2例携带胚系PTPN11突变的NS-MPD患者仍在监测中。NS-MPD患者因均未接受化疗干预而被排除在治疗分析之外。所有接受5-氮杂胞苷单药治疗的患者（5/5）及4例接受6-巯基嘌呤单药治疗患者中的1例，其突变等位基因频率均出现下降。2例患者转化为急性髓系白血病并最终死亡。在接受移植的患者中，7/13存活，3/13出现移植后复发，中位复发时间为3.55个月。本研究报告揭示了JMML不同遗传亚型的治疗反应及长期预后，并为携带胚系PTPN11突变的NS-MPD患者自发缓解的预期时间提供了参考依据。

原文链接：

Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience