Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Division of Hematology and Medical Oncology, Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York, NY.
Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):e507-e520. doi: 10.1016/j.clml.2022.01.016. Epub 2022 Feb 5.
Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm, characterized by pathologic myeloproliferation associated with inflammatory and pro-angiogenic cytokine release, that results in functional compromise of the bone marrow. Thrombocytopenia is a disease-related feature of MF, which portends a poor prognosis impacting overall survival (OS) and leukemia free survival. Thrombocytopenia in MF has multiple causes including ineffective hematopoiesis, splenic sequestration, and treatment-related effects. Presently, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curable treatment for MF, which, unfortunately, is only a viable option for a minority of patients. All other currently available therapies are either focused on improving cytopenias or the alleviating systemic symptoms and burdensome splenomegaly. While JAK2 inhibitors have moved to the forefront of MF therapy, available JAK inhibitors are advised against in patients with severe thrombocytopenia (platelets < 50 × 10/L). In this review, we describe the pathogenesis, prevalence, and prognostic significance of thrombocytopenia in MF. We also explore the value and limitations of treatments directed at addressing cytopenias, splenomegaly and symptom burden, and those with potential disease modification. We conclude by proposing a treatment algorithm for patients with MF and severe thrombocytopenia.
骨髓纤维化（MF）是一种克隆性造血干细胞肿瘤，其特征是病理性髓系增殖，伴有炎症和促血管生成细胞因子的释放，导致骨髓功能受损。血小板减少症是 MF 的一种与疾病相关的特征，预示着预后不良，影响总生存（OS）和无白血病生存。MF 中的血小板减少症有多种原因，包括无效造血、脾脏隔离和治疗相关影响。目前，异基因造血干细胞移植（HSCT）仍然是 MF 唯一可治愈的治疗方法，但不幸的是，只有少数患者可行该治疗。目前所有其他可用的治疗方法要么侧重于改善细胞减少症，要么缓解全身症状和沉重的脾肿大。虽然 JAK2 抑制剂已成为 MF 治疗的前沿，但严重血小板减少症（血小板<50×10/L）患者不建议使用现有的 JAK 抑制剂。在这篇综述中，我们描述了 MF 中血小板减少症的发病机制、流行率和预后意义。我们还探讨了针对细胞减少症、脾肿大和症状负担以及具有潜在疾病修饰作用的治疗方法的价值和局限性。最后，我们提出了一种针对 MF 伴严重血小板减少症患者的治疗算法。
