Objective: To investigate the clinical characteristics, prognostic factors and efficacy of hypomethylating agent (HMA) in patients with chronic myelomonocytic leukemia (CMML).
Methods: The clinical data of 37 newly diagnosed patients with CMML was analyzed retrospectively, and their clinical characteristics and the efficacy of HMA were summarized. Kaplan-Meier and Log-rank test were used for univariate survival analysis, and Cox proportional hazards regression model was used for multivariate analysis.
Results: The median age at diagnosis was 67 years old. Their common manifestations included fatigue, bleeding, abnormal blood routine and fever. Most patients had splenomegaly. According to FAB classification, there were 6 cases of myelodysplastic CMML and 31 cases of myeloproliferative CMML, while according to WHO classification, 8 patients belonged to CMML-0, 9 patients to CMML-1 and 20 patients to CMML-2. At the time of diagnosis, the median white blood cell count was 32.84×109/L, median hemoglobin (Hb) was 101 g/L, median platelet count was 65×109/L, median absolute monocyte count was 9.53×109//L, median absolute neutrophil count (ANC) was 11.29×109//L and median lactate dehydrogenase (LDH) was 374 U/L. Cytogenetic abnormalities were found in 4 cases among the 31 patients who underwent karyotype analysis or fluorescence in situ hybridization detection. There were 12 patients who had analyzable results and gene mutations were identified in 11 cases, including ASXL1, NRAS, TET2, SRSF2 and RUNX1. Among the 6 patients who were treated with HMA and could be evaluated for efficacy, 2 patients achieved complete remission, 1 patient achieved partial remission and 2 patients achieved clinical benefit. Compared with the non-HMA treatment group, overall survival (OS) time was not significantly prolonged in the HMA treatment group. Univariate analysis showed that Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and peripheral blood (PB) blasts ≥5% were significantly associated with poor OS, while WHO classification CMML-2, Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and PB blasts≥5% were significantly associated with poor leukemia-free survival (LFS) (P<0.05). Multivariate analysis showed that ANC≥12×109/L and PB blasts≥5% were significantly associated with poor OS and LFS (P<0.05).
Conclusion: CMML has high heterogeneity in clinical characteristics, genetic changes, prognosis and treatment response. HMA can not significantly improve the survival of CMML patients. ANC≥12×109/L and PB blasts≥5% are independent prognostic factors of OS and LFS in patients with CMML.
题目: 慢性粒-单核细胞白血病患者临床特征及生存分析.
目的: 探讨慢性粒-单核细胞白血病（CMML）患者的临床特征、预后因素和去甲基化药物（HMA）的疗效。.
方法: 对37例初诊CMML患者的临床资料进行回顾性分析，总结其临床特征和HMA的疗效，应用Kaplan-Meier法和Log-rank检验进行单因素生存分析，Cox比例风险回归模型进行多因素分析。.
结果: 患者中位发病年龄为67岁，常见症状包括乏力、出血、血象异常、发热等，多数患者存在脾大。根据FAB分型，发育异常型CMML 6例，增殖型CMML 31例；根据WHO分型，CMML-0 8例，CMML-1 9例，CMML-2 20例。诊断时中位白细胞计数32.84×109/L，中位血红蛋白浓度（Hb）101 g/L，中位血小板计数65×109/L，中位单核细胞绝对值9.53×109/L，中位中性粒细胞绝对值（ANC）11.29×109/L，中位乳酸脱氢酶（LDH）水平374 U/L。31例进行染色体核型分析或荧光原位杂交检测的患者中4例存在细胞遗传学异常，可分析结果的12例患者中11例存在基因突变，常见的有ASXL1、NRAS、TET2、SRSF2和RUNX1等。接受HMA治疗并可评估疗效的6例患者中2例达到完全缓解，1例达部分缓解，2例达临床获益，与非HMA治疗组相比总生存期（OS）无显著延长。单因素分析显示Hb<100 g/L、ANC≥12×9/L、LDH≥250 U/L、外周血原始细胞比例≥5%与较差的OS显著相关，WHO分型CMML-2、Hb<100 g/L、ANC≥12×109/L、LDH≥250 U/L、外周血原始细胞比例≥5%与较差的无白血病生存期（LFS）显著相关（P<0.05）；多因素分析显示ANC≥12×109/L和外周血原始细胞比例≥5%与较差的OS和LFS显著相关（P<0.05）。.
结论: CMML在临床特征、遗传学改变、预后和治疗反应等方面具有高度异质性，HMA未能显著改善患者的生存情况，ANC≥12×109/L、外周血原始细胞比例≥5%为OS、LFS较差的独立预后因素。.
Keywords: chronic myelomonocytic leukemia; efficacy; gene mutation; hypomethylating agent; prognosis.