慢性粒单核细胞白血病实验室特点及预后分析
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摘要
目的分析慢性粒-单核细胞白血病(chronic myelomonocytic leukaemia,CMML)实验室检查特点及预后情况。方法收集2008年3月至2016年6月承德医学院附属医院收治的18例CMML患者的病例资料,按WHO造血和淋巴组织肿瘤分类2016修订版将研究对象分为3组:CMML-0组5例、CMML-1组6例、CMML-2组7例。分析患者的血常规、骨髓形态学、染色体核型、流式细胞检查、分子生物学检测结果,利用Kaplan-Meier绘制生存曲线进行总体、分组分析,同时应用Log-rank检验对3组生存曲线进行比较。结果骨髓及外周血成熟单核细胞比例增高,病态造血病例占61%(11/18)。染色体核型异常率14.3%(2/14)。多参数流式细胞检测成熟单核细胞群(17.40±12.68)%,有CD56,CD16,CD2抗原异常表达;HLA-DR,CD13,CD15表达减弱或缺失;可见CD14拖尾现象。融合基因检测BCR-ABL均阴性。有随访资料的17例患者中6例死亡,3例进展为急性白血病,总体中位生存期21个月。各组中位生存期比较:CMML-0>CMML-1>CMML-2(P<0.05)。结论 CMML单核细胞比例、绝对值增高,形态变异性大。流式细胞检查成熟单核细胞CD56异常表达、HLA-DR表达减弱多见。染色体核型异常检出率低,基因突变检出率高。多种检查指标的联合应用,更能提高诊断的准确性。患者生存期短,预后较差,原始细胞比例是决定生存期重要的因素。
Objective To analyze laboratory characteristics and prognosis of chronic myelomonocytic leukaemia(CMML). Methods Clinical data of 18 CMML patients, who were treated in the Affiliated Hospital of Chengde Medical College from March 2008 to June 2016, were collected. The patients were divided into three groups according to the 2016 revision of World Health Organization classification of myeloid neoplasms and acute leukemia: CMML-0(n=5), CMML-1(n=6) and CMML-2(n=7). Retrospective analysis was performed on blood routine, bone marrow morphology, chromosome karyotype, flow cytometry and molecular tests. Kaplan-Meier survival curves were generated for overall and fractional analysis. Comparison of the survival curves among the three groups was performed by Log-rank test. Results The majority of the CMML patients were elderly man. The proportion of mature monocytes in bone marrow and peripheral blood was increased, and myelodysplasia was observed in 61% of the cases. The abnormal rate of chromosome karyotype was 14.3%. Multiparameter flow cytometry was used to detect the mature mononuclear cell group(17.40±12.68)%. This group of cells had aberrant expression of CD56, CD2, and CD16, and lacked or had decreased expression of HLA-DR,CD13,CD15, and the phenomenon of CD14 smearing. All cases were negative for BCR-ABL fusion gene. Seventeen patients were followed. Among them, 6 patients were dead and 3 patients progressed to acute myeloid leukemia(AML). The median survival time was 21-months. Comparison of the median survival time among the three groups revealed CMML-0>CMML-1>CMML-2(P<0.05). Conclusion The proportion and absolute number of monocytes increase with morphologic dysplasia. Flow cytometry shows abnormal expression of CD56 and decreased expression of HLA-DR in mature monocytes. The detection rate of chromosome karyotype abnormality is low, and the detection rate of gene mutation is high. Combination of multiple laboratory examinations can improve the accuracy of diagnosis. The survival time of patients is short and the prognosis is poor. The ratio of monoblast is an important factor to determine the survival time.
Objective To analyze laboratory characteristics and prognosis of chronic myelomonocytic leukaemia(CMML). Methods Clinical data of 18 CMML patients, who were treated in the Affiliated Hospital of Chengde Medical College from March 2008 to June 2016, were collected. The patients were divided into three groups according to the 2016 revision of World Health Organization classification of myeloid neoplasms and acute leukemia: CMML-0(n=5), CMML-1(n=6) and CMML-2(n=7). Retrospective analysis was performed on blood routine, bone marrow morphology, chromosome karyotype, flow cytometry and molecular tests. Kaplan-Meier survival curves were generated for overall and fractional analysis. Comparison of the survival curves among the three groups was performed by Log-rank test. Results The majority of the CMML patients were elderly man. The proportion of mature monocytes in bone marrow and peripheral blood was increased, and myelodysplasia was observed in 61% of the cases. The abnormal rate of chromosome karyotype was 14.3%. Multiparameter flow cytometry was used to detect the mature mononuclear cell group(17.40±12.68)%. This group of cells had aberrant expression of CD56, CD2, and CD16, and lacked or had decreased expression of HLA-DR,CD13,CD15, and the phenomenon of CD14 smearing. All cases were negative for BCR-ABL fusion gene. Seventeen patients were followed. Among them, 6 patients were dead and 3 patients progressed to acute myeloid leukemia(AML). The median survival time was 21-months. Comparison of the median survival time among the three groups revealed CMML-0>CMML-1>CMML-2(P<0.05). Conclusion The proportion and absolute number of monocytes increase with morphologic dysplasia. Flow cytometry shows abnormal expression of CD56 and decreased expression of HLA-DR in mature monocytes. The detection rate of chromosome karyotype abnormality is low, and the detection rate of gene mutation is high. Combination of multiple laboratory examinations can improve the accuracy of diagnosis. The survival time of patients is short and the prognosis is poor. The ratio of monoblast is an important factor to determine the survival time.
引文
[1] 周小鸽,陈辉树,郝玉书,等.造血与淋巴组织肿瘤WHO分类[M].第4版.诊断病理学杂志社,2011:93-97.
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[6] 王韫秀,张继红,胡延平,等.多参数流式细胞术在慢性粒单核细胞白血病、骨髓增生异常综合症及急性单核细胞白血病免疫表型鉴别中的应用及其意义[J].中国实验血液学杂志,2012,(4):857-862.
[7] Talati C,Zhang L,Shaheen G,et al.Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis[J].Blood,2017,129(13):1881-1883.
[8] Patnaik MM,Tefferi A.Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia[J].Blood Cancer J,2016,6:e393.
[9] 陆滢,余梦霞,牧启田,等.41例慢性粒单核细胞白血病患者染色体核型特征和预后分析[J].中华医学遗传学杂志,2013,(2):134-137.
[10] Tang G,Zhang L,Fu B,et al.Cytogenetic risk stratification of 417 patients with chronic myelomonocytic leukemia from a single institution[J].Am J Hematol,2014,89(8):813-818.
[11] 武英伟,张志华,张茉莉.复杂变异易位的慢性粒细胞白血病遗传学检查特点及预后分析[J].广东医学,2016,37(7):1021-1023.
[12] Padron E,Garcia-Manero G,Patnaik MM,et al.An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies[J].Blood Cancer J,2015,5:e333.
[13] Patnaik MM,Itzykson R,Lasho TL,et al.ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia:a two-Center study of 466 patients[J].Leukemia,2014,28(11):2206-2212.
[14] Cui Y,Tong H,Du X,et al.Impact of TET2,SRSF2,ASXL1 and SETBP1 mutations on survival of patients with chronic myelomonocytic leukemia[J].Blood Cancer J,2016,6:e385.
[15] Wassie EA,Itzykson R,Lasho TL,et al.Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia:a Mayo C1inic-French Consortium Study[J].Am J Hematol,2014,89(12):1111-1115.
[16] Gelsi-Boyer V,Brecqueville M,Devillier R,et al.Mutations in ASXLl areassociated with poor prognosis across the spectrum of malignant myeloid diseases[J].J Hematol Oncol,2012,5:12.
[17] Patnaik MM,Wassie EA,Lasho TL,et al.Blast transformation in chronic myelomonocytic leukemia:Risk factors,genetic features,survival,and treatment outcome[J].Am J Hematol,2015,90(5):411-416.
[2] 张之南,沈悌.血液病诊断及疗效标准[M].第3版.北京:科学出版社,2007:134-138.
[3] Arber DA,Orazi A,Hasserjian R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J].Blood,2016,27(20):2391-2405.
[4] 张春营,吴晓雄.慢性粒单核细胞白血病[J].临床军医杂志,2008,36(2):288-290.
[5] 曹方方,刘静,彭冲,等.免疫分型在慢性粒单核细胞白血病诊断及鉴别中的应用[J].临床检验杂志,2017,(5):353-355.
[6] 王韫秀,张继红,胡延平,等.多参数流式细胞术在慢性粒单核细胞白血病、骨髓增生异常综合症及急性单核细胞白血病免疫表型鉴别中的应用及其意义[J].中国实验血液学杂志,2012,(4):857-862.
[7] Talati C,Zhang L,Shaheen G,et al.Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis[J].Blood,2017,129(13):1881-1883.
[8] Patnaik MM,Tefferi A.Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia[J].Blood Cancer J,2016,6:e393.
[9] 陆滢,余梦霞,牧启田,等.41例慢性粒单核细胞白血病患者染色体核型特征和预后分析[J].中华医学遗传学杂志,2013,(2):134-137.
[10] Tang G,Zhang L,Fu B,et al.Cytogenetic risk stratification of 417 patients with chronic myelomonocytic leukemia from a single institution[J].Am J Hematol,2014,89(8):813-818.
[11] 武英伟,张志华,张茉莉.复杂变异易位的慢性粒细胞白血病遗传学检查特点及预后分析[J].广东医学,2016,37(7):1021-1023.
[12] Padron E,Garcia-Manero G,Patnaik MM,et al.An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies[J].Blood Cancer J,2015,5:e333.
[13] Patnaik MM,Itzykson R,Lasho TL,et al.ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia:a two-Center study of 466 patients[J].Leukemia,2014,28(11):2206-2212.
[14] Cui Y,Tong H,Du X,et al.Impact of TET2,SRSF2,ASXL1 and SETBP1 mutations on survival of patients with chronic myelomonocytic leukemia[J].Blood Cancer J,2016,6:e385.
[15] Wassie EA,Itzykson R,Lasho TL,et al.Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia:a Mayo C1inic-French Consortium Study[J].Am J Hematol,2014,89(12):1111-1115.
[16] Gelsi-Boyer V,Brecqueville M,Devillier R,et al.Mutations in ASXLl areassociated with poor prognosis across the spectrum of malignant myeloid diseases[J].J Hematol Oncol,2012,5:12.
[17] Patnaik MM,Wassie EA,Lasho TL,et al.Blast transformation in chronic myelomonocytic leukemia:Risk factors,genetic features,survival,and treatment outcome[J].Am J Hematol,2015,90(5):411-416.