Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Am J Hematol. 2011 Apr;86(4):362-71. doi: 10.1002/ajh.21982.
Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.
The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.
The prognostic relevance of the 2008 World Health Organization (WHO) classification of SM has recently been confirmed. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non-MC lineage disease (SM-AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.
RISK-ADAPTED THERAPY: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom-directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease-related organ dysfunction; interferon-α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator-release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Treatment of SM-AHNMD is governed primarily by the non-MC neoplasm; hydroxyurea has modest utility in this setting. Dasatinib's in vitro anti- KITD816V activity has not translated into significant therapeutic activity in most SM patients. In contrast, preliminary data suggest that Midostaurin may produce significant decreases in MC burden in some patients.
系统性肥大细胞增多症（SM）是由于一个或多个皮肤外器官中异常肥大细胞（MC）的克隆性增殖引起的。
主要标准是骨髓中存在形态异常的 MC 多发性簇状聚集。次要诊断标准包括血清胰蛋白酶水平升高、MC 异常表达 CD25 和/或 CD2，以及存在 KITD816V。
最近已经证实 2008 年世界卫生组织（WHO）SM 分类的预后相关性。将 SM 患者分为惰性（ISM）、侵袭性 SM（ASM）、与克隆性非 MC 谱系疾病相关的 SM（SM-AHNMD）和肥大细胞白血病（MCL）亚组，这是确定预后的有用的第一步。
SM 的治疗通常是姑息性的。ISM 患者预期寿命正常，接受症状导向治疗；对于难治性症状，偶尔可能需要细胞减少治疗。ASM 患者有与疾病相关的器官功能障碍；干扰素-α（±皮质类固醇）可控制皮肤、血液、胃肠道、骨骼和介质释放症状，但耐受性差。同样，克拉屈滨具有广泛的治疗活性，在需要快速 MC 减容时特别有用；主要毒性是骨髓抑制。伊马替尼在存在伊马替尼敏感的 KIT 突变或 KITD816 未突变的患者中具有治疗作用。SM-AHNMD 的治疗主要由非 MC 肿瘤决定；羟基脲在这种情况下具有一定的作用。达沙替尼在体外的抗 KITD816V 活性并未转化为大多数 SM 患者的显著治疗活性。相比之下，初步数据表明米哚妥林可能会使一些患者的 MC 负荷显著降低。
