Sumbly Vikram, Landry Ian, Iqbal Saba, Bhatti Zamaraq, Alshamam Mohsen S, Ashfaq Salman, Rizzo Vincent
Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals, Queens, USA.
Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals, Queens, USA.
Cureus. 2021 Sep 29;13(9):e18385. doi: 10.7759/cureus.18385. eCollection 2021 Sep.
Systemic mastocytosis is a rare hematologic disorder characterized by the clonal proliferation of mast cells in extra-cutaneous organs. This disease can be further subdivided into five different phenotypes: indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL). The tyrosine kinase inhibitor (and also potent KIT D816V inhibitor) avapritinib, initially approved for the treatment of gastrointestinal stromal tumors (GISTs) bearing a PDGFRA exon 18 mutation, also showed great promise in patients with systemic mastocytosis, a disease known to be driven by a mutation in KIT (D816V). We present an overview of this rare disorder, including a review of the current understanding of the genetic mechanisms which lead to the disease state, the action of the tyrosine kinase inhibitors, as well as the latest clinical trial data which led to the current recommendations for the use of avapritinib.
系统性肥大细胞增多症是一种罕见的血液系统疾病，其特征为皮肤外器官中肥大细胞的克隆性增殖。这种疾病可进一步细分为五种不同的表型：惰性系统性肥大细胞增多症（ISM）、冒烟性系统性肥大细胞增多症（SSM）、侵袭性系统性肥大细胞增多症（ASM）、伴相关血液系统肿瘤的系统性肥大细胞增多症（SM-AHN）和肥大细胞白血病（MCL）。酪氨酸激酶抑制剂（也是强效KIT D816V抑制剂）阿伐替尼最初被批准用于治疗携带血小板衍生生长因子受体α（PDGFRA）第18外显子突变的胃肠道间质瘤（GIST），在系统性肥大细胞增多症患者中也显示出巨大潜力，已知这种疾病由KIT（D816V）突变驱动。我们概述了这种罕见疾病，包括对导致疾病状态的遗传机制的当前理解、酪氨酸激酶抑制剂的作用，以及产生当前阿伐替尼使用建议的最新临床试验数据。
