103例急性红白血病患者生物学特征与疗效观察
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摘要
目的:本研究总结分析急性红白血病(AEL)的生物学特征与疗效。方法:回顾性分析2009年6月至2016年5月收治的103例急性红白血病患者肝功能、乳酸脱氢酶、凝血、形态学、免疫学、细胞遗传学及分子生物学特征,通过缓解率、复发率、无复发生存及总生存等指标观察疗效。结果:白细胞、粒细胞、血红蛋白及血小板中位数分别为3.04×10~9/L、0.67×10~9/L、66 g/L及45.0×10~9/L,71.1%的患者外周血涂片可以发现有核红细胞,无1例患者出现凝血功能异常,患者主要表达:CD13(93.5%)、CD117(89.1%)、HLA-DR(87.0%)、CD34(80.0%),部分患者表达淋系抗原CD4(42.9%)及CD7(28.9%)。82例患者核型分析显示,正常核型52.4%(43/82),异常核型41.5%(34/82),检查失败6.1%(5/82)。34例异常核型中,简单异常41.2%(14/34),复杂核型58.8%(20/34)。对60例患者检测融合基因显示,阳性率为16.7%(10/60)。27例患者检测预后基因突变显示,阳性率为77.8%(21/27)。初诊急性红白血病103例中接受化疗81例,可进行疗效分析66例。2个疗程累积缓解率45.5%(30/66),复发率36.7%(11/30),中位复发时间15.5(6.2-50)个月。可进行疗效分析66例患者中位生存时间为29个月。CR(30例)患者截至随访结束未达中位生存时间,明显优于未获CR(36例)患者12个月(P=0.001)。CR患者5年生存率65%,无复发生存(RFS)中位时间46.2个月,3年RFS为58%。结论:AEL患者具有高表达CD34抗原、多为复杂核型等生物学特点。虽然AEL患者缓解率低,生存期短,但缓解患者人群具有较好的长生存及良好的生存质量。
Objective: To investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia( AEL,AML-M6). Methods: Blood cell count,liver function,lactate dehydrogenase level,coagulation,morphology,immunology,cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate,relapse rate,relapse-free survival and overall survival. Results: The medians of white blood cells,granulocyte,hemoglobin and platelet were 3. 04 ×10~9/L,0. 67 ×10~9/L,66 g/L,and 45 ×10~9/L,respectively.Nucleated red blood cells were found in the peripheral blood smears from 71. 1% of AEL patients. None of the patients showed abnormal coagulation function. Flow cytometry analysis indicated that CD13( 93. 5%),CD117( 89. 1%),HLA-DR( 87. 0%),and CD34( 80. 0%) were highly expressed in AEL,and lymphoid antigens of CD4( 42. 9%) and CD7( 28. 9%) were expressed in partial patients. Karyotype analysis in 82 patients showed 52. 4%( 43/82) normal karyotype,41. 5%( 34/82) abnormal karyotype,and 6. 1%( 5/82) failed tests. In the 34 cases with abnormal karyotype,there were 14( 41. 2%) cases with simple chromosomal abnomality and 20( 58. 8%) cases with complex karyotype. The positive rate of fusion gene accounted for 16. 7% in 60 patients,and the gene mutations accounted for77. 8% in 27 patients. Among 103 cases of AEL,81 cases were treated with chemotherapy,but 66 cases can be used for therapeutic analysis,as a results the total complete remission rate derived from 2 courses of treatment was 45. 5%( 30/66). The relapse rate was 6. 7%( 11/30),and the median relapse time was 5. 5 months(. 2-50 months). The median survival time of 66 patients for therapeutic analysis was 29 months. The median survival time of CR patients was very significantly longer than that of the non-CR patients( P = 0. 001). The 5 year survival rate of CR patients was 65%,the median time of relapse-free survival( RFS) was 46. 2 months and 3-years RFS was 58%. Conclusion: AEL is characterized by the highly expressed CD34 antigen,and complex karyotype. Although AEL has lower CR rate and poor prognosis,CR patients can achieve long-term survival and have good quality of life.
Objective: To investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia( AEL,AML-M6). Methods: Blood cell count,liver function,lactate dehydrogenase level,coagulation,morphology,immunology,cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate,relapse rate,relapse-free survival and overall survival. Results: The medians of white blood cells,granulocyte,hemoglobin and platelet were 3. 04 ×10~9/L,0. 67 ×10~9/L,66 g/L,and 45 ×10~9/L,respectively.Nucleated red blood cells were found in the peripheral blood smears from 71. 1% of AEL patients. None of the patients showed abnormal coagulation function. Flow cytometry analysis indicated that CD13( 93. 5%),CD117( 89. 1%),HLA-DR( 87. 0%),and CD34( 80. 0%) were highly expressed in AEL,and lymphoid antigens of CD4( 42. 9%) and CD7( 28. 9%) were expressed in partial patients. Karyotype analysis in 82 patients showed 52. 4%( 43/82) normal karyotype,41. 5%( 34/82) abnormal karyotype,and 6. 1%( 5/82) failed tests. In the 34 cases with abnormal karyotype,there were 14( 41. 2%) cases with simple chromosomal abnomality and 20( 58. 8%) cases with complex karyotype. The positive rate of fusion gene accounted for 16. 7% in 60 patients,and the gene mutations accounted for77. 8% in 27 patients. Among 103 cases of AEL,81 cases were treated with chemotherapy,but 66 cases can be used for therapeutic analysis,as a results the total complete remission rate derived from 2 courses of treatment was 45. 5%( 30/66). The relapse rate was 6. 7%( 11/30),and the median relapse time was 5. 5 months(. 2-50 months). The median survival time of 66 patients for therapeutic analysis was 29 months. The median survival time of CR patients was very significantly longer than that of the non-CR patients( P = 0. 001). The 5 year survival rate of CR patients was 65%,the median time of relapse-free survival( RFS) was 46. 2 months and 3-years RFS was 58%. Conclusion: AEL is characterized by the highly expressed CD34 antigen,and complex karyotype. Although AEL has lower CR rate and poor prognosis,CR patients can achieve long-term survival and have good quality of life.
引文
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2 Liu CJ,Hong YC,Yang CF,et al.Clinicopathologic features and outcome of acute erythroid leukemia based on 2008 revised World Health Organization classification.Leuk Lymphoma,2012;53(2):289-294.
3 Mori M,Sprague J.The successful remission induction by sorafenib and long-term complete remission in a FLT3-ITD-positive patient with a refractory acute erythroid leukemia and abnormal cytogenetics.Leuk Res,2012;36(1):e1-3.
4 Dameshek W,Baldini M.The Di Guglielmo syndrome,Blood,1958;13(2):192-194.
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6 Bene MC,Castoldi G,Knapp W,et al.Proposals for the immunological classification of acute leukemias.European Group for the Immunological Characterization of Leukemias(EGIL).Leukemia,1995;9(10):1783-1786.
7 程晓文,马红霞,陈珏,等.成人急性髓性白血病细胞CD表型与预后的关系.现代免疫学,2005;25(1):70-77.
8 郭玥潞,周敏航,曹婷婷,等.急性红白血病13例临床特点及预后分析.中国实验血液学杂志,2013;21(5):1142-1147.
9 Santos FP,Bueso-Ramos CE,Ravandi F.Acute erythroleukemia:diagnosis and management.Expert Rev Hematol,2010;3(6):705-718.
10 李超,钱新华,千新来,等.黄芪多糖对人红白血病K562细胞凋亡的影响.郑州大学学报(医学版),2014;49(5):641-644.
11 王清霞,张秋堂,岳保红,等.成人急性髓性白血病免疫学表型分析.郑州大学学报(医学版),2008;43(4):779-781.
12 程文秀,孙爱宁,陈苏宁,等.167例急性红白血病患者临床特征及预后分析.中华血液学杂志,2014;35(11):970-973.
13 柳金,陆道培,张艳.急性红白血病55例染色体特征和预后分析.中华内科杂志,2006;45(9):738-740
14 费新红,武淑兰,赵杰,等.急性红白血病64例生物学特点及预后分析.临床血液学杂志,2012;25(4):488-491.
15 曾蓉,陈燕.急性红白血病的生物学特征与临床疗效研究.中国实验血液学杂志,2007;15(3):466-469.
16 张静人,刘跃均,仇惠英,等.地西他滨联合CAG预激方案治疗急性红白血病55例临床研究.中国实验内科杂志,2014;34(11):1103-1105.
2 Liu CJ,Hong YC,Yang CF,et al.Clinicopathologic features and outcome of acute erythroid leukemia based on 2008 revised World Health Organization classification.Leuk Lymphoma,2012;53(2):289-294.
3 Mori M,Sprague J.The successful remission induction by sorafenib and long-term complete remission in a FLT3-ITD-positive patient with a refractory acute erythroid leukemia and abnormal cytogenetics.Leuk Res,2012;36(1):e1-3.
4 Dameshek W,Baldini M.The Di Guglielmo syndrome,Blood,1958;13(2):192-194.
5 Hasserjian RP,Zuo Z,Garcia C,et al.Acute erythroid leukemia:a reassessment using criteria refined in the 2008 WHO classification.Blood,2010;115(10):1985-1992.
6 Bene MC,Castoldi G,Knapp W,et al.Proposals for the immunological classification of acute leukemias.European Group for the Immunological Characterization of Leukemias(EGIL).Leukemia,1995;9(10):1783-1786.
7 程晓文,马红霞,陈珏,等.成人急性髓性白血病细胞CD表型与预后的关系.现代免疫学,2005;25(1):70-77.
8 郭玥潞,周敏航,曹婷婷,等.急性红白血病13例临床特点及预后分析.中国实验血液学杂志,2013;21(5):1142-1147.
9 Santos FP,Bueso-Ramos CE,Ravandi F.Acute erythroleukemia:diagnosis and management.Expert Rev Hematol,2010;3(6):705-718.
10 李超,钱新华,千新来,等.黄芪多糖对人红白血病K562细胞凋亡的影响.郑州大学学报(医学版),2014;49(5):641-644.
11 王清霞,张秋堂,岳保红,等.成人急性髓性白血病免疫学表型分析.郑州大学学报(医学版),2008;43(4):779-781.
12 程文秀,孙爱宁,陈苏宁,等.167例急性红白血病患者临床特征及预后分析.中华血液学杂志,2014;35(11):970-973.
13 柳金,陆道培,张艳.急性红白血病55例染色体特征和预后分析.中华内科杂志,2006;45(9):738-740
14 费新红,武淑兰,赵杰,等.急性红白血病64例生物学特点及预后分析.临床血液学杂志,2012;25(4):488-491.
15 曾蓉,陈燕.急性红白血病的生物学特征与临床疗效研究.中国实验血液学杂志,2007;15(3):466-469.
16 张静人,刘跃均,仇惠英,等.地西他滨联合CAG预激方案治疗急性红白血病55例临床研究.中国实验内科杂志,2014;34(11):1103-1105.