背景:慢性粒单核细胞白血病(CMML)是一种克隆性造血干细胞疾病,具有骨髓增生异常综合征和骨髓增殖性肿瘤的重叠特征,以突出的单核细胞增多和白血病转化的固有风险为特征(3-5年内约15%-20%)。
方法:新修订的诊断标准包括持续(>3个月)外周血(PB)单核细胞增多(≥0.5×109/L;单核细胞≥白细胞计数的10%),一致的骨髓(BM)形态,<20%BM或PB母细胞(包括前单核细胞),和克隆性的细胞遗传学或分子证据。细胞遗传学异常发生在约30%的患者中,而>95%有体细胞突变:TET2(~60%),SRSF2(~50%),ASXL1(~40%),RAS途径(~30%),和其他人。ASXL1和DNMT3A突变的存在和TET2突变的不存在对总体存活产生负面影响(ASXL1WT/TET2MT基因型是有利的)。
方法:几种风险模型在识别高危患者中起到了相似的作用,这些高危患者被考虑进行异基因干细胞移植(ASCT)。Mayo分子模型(MMM)中的风险因素包括存在截短的ASXL1突变,绝对单核细胞计数>10×109/L,血红蛋白<10g/dL,血小板计数<100×109/L,和循环未成熟骨髓细胞的存在;由此产生的4级风险分类包括高(≥3个风险因素),中间-2(2个风险因素),中间-1(1个危险因素),和低(无危险因素);相应的中位生存期分别为16、31、59和97个月.CMML也被归类为“骨髓增生性(MP-CMML)”或“骨髓增生异常(MD-CMML)”,“基于白细胞计数的存在或不存在≥13×109/L。
方法:ASCT是确保治愈或长期生存的唯一治疗方式,适用于MMM高/中-2风险疾病。药物治疗目前没有改变疾病,包括羟基脲和低甲基化药物;最近的一项比较羟基脲和地西他滨的3期研究(DACOTA),在高风险MP-CMML中,23.1和18.4个月的总生存期相似,分别,尽管地西他滨的反应率较高(56%vs.31%)。
■这些包括全身性炎症性自身免疫性疾病,皮肤白血病和溶菌酶诱导的肾病;后者需要在白细胞增多期间密切监测肾功能,是细胞减灭性治疗的潜在指征。
BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, characterized by prominent monocytosis and an inherent risk for leukemic transformation (~15%-20% over 3-5 years).
METHODS: Newly revised diagnostic criteria include sustained (>3 months) peripheral blood (PB) monocytosis (≥0.5 × 109/L; monocytes ≥10% of leukocyte count), consistent bone marrow (BM) morphology, <20% BM or PB blasts (including promonocytes), and cytogenetic or molecular evidence of clonality. Cytogenetic abnormalities occur in ~30% of patients, while >95% harbor somatic mutations: TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), RAS pathway (~30%), and others. The presence of ASXL1 and DNMT3A mutations and absence of TET2 mutations negatively impact overall survival (ASXL1WT/TET2MT genotype being favorable).
METHODS: Several risk models serve similar purposes in identifying high-risk patients that are considered for allogeneic stem cell transplant (ASCT) earlier than later. Risk factors in the Mayo Molecular Model (MMM) include presence of truncating ASXL1 mutations, absolute monocyte count >10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L, and the presence of circulating immature myeloid cells; the resulting 4-tiered risk categorization includes high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor), and low (no risk factors); the corresponding median survivals were 16, 31, 59, and 97 months. CMML is also classified as being \"myeloproliferative (MP-CMML)\" or \"myelodysplastic (MD-CMML),\" based on the presence or absence of leukocyte count of ≥13 × 109/L.
METHODS: ASCT is the only treatment modality that secures cure or long-term survival and is appropriate for MMM high/intermediate-2 risk disease. Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%).
UNASSIGNED: These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.