48例急性混合细胞表型白血病患者的临床特征及预后
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摘要
目的分析急性混合细胞表型白血病(MPAL)临床特点、生物学特征、疗效及预后。方法根据2008年WHO血液肿瘤分类标准,回顾性分析了48例M PAL患者(M PAL组)的病历资料,以同期50例伴淋系抗原表达的AML(Ly+AML)患者(Ly+AML组)作为对照。采用常规瑞士染色及细胞化学染色进行细胞形态学分析,采用流式细胞术进行细胞免疫分型,采用荧光原位杂交技术检测白血病常见融合基因,采用常规G显带技术分析染色体核型。结果 MPAL组发病中位年龄显著大于Ly+AML组(54岁vs 30岁,P<0.05),其CD34阳性率、异常染色体核型发生率及Ph染色体核型发生率也显著高于Ly+AML组(85.4%vs 50.0%,65.3%vs 35.7%,23.0%vs 0%,P均<0.05)。M PAL总体生存时间(OS)及无复发生存时间(RFS)均显著低于Ly+AM L组(P<0.05)。结论与Ly+AM L患者相比,M PAL患者的OS及RFS短,其预后不良可能与年龄、CD34高表达、Ph染色体阳性率高等因素有关。
Objective To investigate the clinical and biological characteristics and prognosis of mixed phenotype acute leukemia( MPAL). Methods Forty-eight patients diagnosed with MPAL( MPAL group) by WHO 2008 criteria and50 patients diagnosed with Ly + AML( Ly + AML group),which is defined as the control group,in the same period were retrospectively analyzed. The cell morphology analysis was performed by swiss and cytochemical staining,the cell immunophenotype was detected by the flowcytometry,the fusion gene of leukemia was detected by fluorescence in situ hybridization,and the chromosome karyotype was analyzed by the standard technique of G-banding. Results The median age of MPAL group was larger than that of Ly + AML group significantly( 54 y vs 30 y,P < 0. 05). The incidence of CD34 positive expression,bnormal karyotype and ph+ in the MPAL group were significantly higher than those in the Ly + AML group( 85. 4% vs 50%,65. 3% vs 35. 7%,23% vs 0%,all P < 0. 05). The OS and RFS of MPAL group were significantely lower than those of Ly + AML group( both P < 0. 05). Conclusion Compared with Ly +AML group,MPAL group has lower OS and RFS; the poor prognosis of MPAL may due to the age,and high incidence of CD34 positive expression and ph+.
Objective To investigate the clinical and biological characteristics and prognosis of mixed phenotype acute leukemia( MPAL). Methods Forty-eight patients diagnosed with MPAL( MPAL group) by WHO 2008 criteria and50 patients diagnosed with Ly + AML( Ly + AML group),which is defined as the control group,in the same period were retrospectively analyzed. The cell morphology analysis was performed by swiss and cytochemical staining,the cell immunophenotype was detected by the flowcytometry,the fusion gene of leukemia was detected by fluorescence in situ hybridization,and the chromosome karyotype was analyzed by the standard technique of G-banding. Results The median age of MPAL group was larger than that of Ly + AML group significantly( 54 y vs 30 y,P < 0. 05). The incidence of CD34 positive expression,bnormal karyotype and ph+ in the MPAL group were significantly higher than those in the Ly + AML group( 85. 4% vs 50%,65. 3% vs 35. 7%,23% vs 0%,all P < 0. 05). The OS and RFS of MPAL group were significantely lower than those of Ly + AML group( both P < 0. 05). Conclusion Compared with Ly +AML group,MPAL group has lower OS and RFS; the poor prognosis of MPAL may due to the age,and high incidence of CD34 positive expression and ph+.
引文
[1]Van den Ancker W,Terwijn M,Westers TM,et al.Acute leukemias of ambiguous lineage:diagnostic consequences of the WHO2008 classification[J].Leukemia,2010,24(7):1392-1396.
[2]Bene M,Bernier M,Casasnovas RO,et al.The reliability and specificity of c-kit for the diagnosis of acute mye-loid leukemias and undifferentiated leukemias[J].Blood,1998,92(2):596-599.
[3]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学技术出版社,2007:131-134.
[4]张彦明,吴德沛,孙爱宁,等.混合表型急性白血病32例临床研究[J].中华血液学杂志,2011,32(1):12-16.ZHANG Yanming,WU Depei,SUN Aining,et al.Study on the clinical characteristics of 32 pafients w ith mixed phenotype acute leukemia[J].Chin Hematol,2011,32(1):12-16.
[5]Matutes E,Pickl WF,Vant Veer M,et al.Mixed-phenotype acute leukemia:clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008classification[J].Blood,2011,117(11):3163-3171.
[6]Gritsaev SV,Kostroma II,Riadnova GM,et al.The specific features of diagnosis of mixed-phenotype acute leukemia:a combination of B-cell antigen expressions according to the results of flow cytometry and morphological markers of myeloid differentiation in blast cells:a clinical case[J].Ter Arkh,2015,87(7):97-100.
[7]杨芝红,洪燕燕.流式细胞术诊断急性混合细胞白血病临床意义研究[J].中国现代医学杂志,2013,23(5):67-71.YANG Zhihong,HONG Yanyan.Diagnostic value of flow cytometry in patients w ith acute mixed-lineage leukemia[J].China Journal of M odern M edicine,2013,23(5):67-71.
[8]邓小娟,彭贤贵,王平,等.急性混合细胞白血病的形态学、免疫学及细胞遗传学观察[J].国际输血及血液学杂志,2014,37(1):29-31.
[9]赵广芬,黄先豹,陈艳,等.急性混合细胞白血病44例的诊治分析[J].实用医学杂志,2012,28(3):448-450.
[10]Marcela DC,Martha AI,Guillermo J,et al.Diagnosing and treating mixed phenotype acute leukemia:a multicenter 10-year experience in M exico[J].Ann Hematol,2014,93(4):595-601.
[11]Shi R,Munker R.Survival of patients with mixed phenotype acute leukemias:a large population-based study[J].Leuk Res,2015,39(6):606-616.
[12]Weinberg OK,Seetharam M,Ren L,et al.Mixed phenotype acute leukemia:a study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria[J].Am J Clin Pathol,2014,142(6):803-808.
[13]Bachir F,Zerrouk J,Howard SC,et al.Outcomes in patients w ith mixed phenotype acute leukemia in M orocco[J].J Pediatr Hematol Oncol,2014,36(6):392-397.
[14]Lee JH,Min YH,Chung CW,et al.Prognostic implications of the immunophenotype in biphenotypic acute leukemia[J].Leukemia&Lymphoma,2008,49(4):700-709.
[15]Yan L,Ping N,Zhu M,et al.Clinical,immunophenotypic,cytogenetic,and molecular genetic features in 117adult patients w ith mixed-phenotype acute leukemia defined by WHO-2008 classification[J].Haematologica,2012,97(11):1708-1712.
[16]Atfy M,Al Azizi NM,Elnaggar AM,et al.Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients:And its role in their outcome[J].Leuk Res,2011,35(10):1339-1344.
[17]赵林艳,周结,龚芳,等.异基因造血干细胞移植治疗16例混合表型急性白血病患者临床疗效观察[J].中华血液学杂志,2015,36(11):963-965.ZHAO Linyan,ZHOU Jie,GONG Fang,et al.Clinical efficacy observation of allogeneic hematopoietic stem cell transplantation in 16 patients w ith mixed phenotype acute leukemia[J].Chin Hematol,2015,36(11):963-965.
[18]Xu XQ,Wang JM,Lu SQ,et al.Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison w ith that of acute myeloidleukemia and acute lymphoblastic leukemia:a case series of a Chinese population[J].Haematologica,2009,94(7):919-927.
[19]Eckstein OS,Wang L,Punia JN,et al.Mixed-phenotype acute leukemia(M PAL)exhibits frequent mutations in DNM T3A and activated signaling genes[J].Exp Hematol,2016,44(8):740-744.
[20]Weinberg OK,Arber DA.Mixed-phenotype acute leukemia:historical overview and a new definition[J].Leukemia,2010,24(11):1844-1851.
[21]Lee JY,Lee SM,Lee JY,et al.Mixed-phenotype acute leukemia treated w ith decitabine[J].Korean J Intern M ed,2016,31(2):406-408.
[22]Stone RM.Transplantation after remission in mixed phenotype acute leukemia:a good idea[J].Biol Blood M arrow Transplant,2016,22(6):971-972.
[23]颜灵芝,陈苏宁,平娜娜,等.15例成人Ph染色体和/或BCR-ABL阳性混合表型急性白血病的临床及实验室特征分析[J].中华实验血液学杂志,2013,21(5):1116-1120.YAN Lingzhi,CHEN Suning,PING Nana,et al.Clinical and laboratorial analysis for 15 adult cases of mixed phenotypic acute leukemia w ith Ph chromosome and/or positive BCR-ABL[J].Journal of Experimental Hematology,2013,21(5):1116-1120.
[24]Tian H,Xu Y,Liu L,et al.Comparison of outcomes in mixed phenotype acute leukemiapatients treated w ith chemotherapy and stem cell transplantation versus chemotherapy alone[J].Leuk Res,2016,45:40-46.
[25]Munker R,Brazauskas R,Wang HL,et al.Allogeneic hematopoietic cell transplantation for patients w ith mixed phenotype acute leukemia[J].Biol Blood M arrow Transplant,2016,22(6):1024-1029.
[2]Bene M,Bernier M,Casasnovas RO,et al.The reliability and specificity of c-kit for the diagnosis of acute mye-loid leukemias and undifferentiated leukemias[J].Blood,1998,92(2):596-599.
[3]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学技术出版社,2007:131-134.
[4]张彦明,吴德沛,孙爱宁,等.混合表型急性白血病32例临床研究[J].中华血液学杂志,2011,32(1):12-16.ZHANG Yanming,WU Depei,SUN Aining,et al.Study on the clinical characteristics of 32 pafients w ith mixed phenotype acute leukemia[J].Chin Hematol,2011,32(1):12-16.
[5]Matutes E,Pickl WF,Vant Veer M,et al.Mixed-phenotype acute leukemia:clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008classification[J].Blood,2011,117(11):3163-3171.
[6]Gritsaev SV,Kostroma II,Riadnova GM,et al.The specific features of diagnosis of mixed-phenotype acute leukemia:a combination of B-cell antigen expressions according to the results of flow cytometry and morphological markers of myeloid differentiation in blast cells:a clinical case[J].Ter Arkh,2015,87(7):97-100.
[7]杨芝红,洪燕燕.流式细胞术诊断急性混合细胞白血病临床意义研究[J].中国现代医学杂志,2013,23(5):67-71.YANG Zhihong,HONG Yanyan.Diagnostic value of flow cytometry in patients w ith acute mixed-lineage leukemia[J].China Journal of M odern M edicine,2013,23(5):67-71.
[8]邓小娟,彭贤贵,王平,等.急性混合细胞白血病的形态学、免疫学及细胞遗传学观察[J].国际输血及血液学杂志,2014,37(1):29-31.
[9]赵广芬,黄先豹,陈艳,等.急性混合细胞白血病44例的诊治分析[J].实用医学杂志,2012,28(3):448-450.
[10]Marcela DC,Martha AI,Guillermo J,et al.Diagnosing and treating mixed phenotype acute leukemia:a multicenter 10-year experience in M exico[J].Ann Hematol,2014,93(4):595-601.
[11]Shi R,Munker R.Survival of patients with mixed phenotype acute leukemias:a large population-based study[J].Leuk Res,2015,39(6):606-616.
[12]Weinberg OK,Seetharam M,Ren L,et al.Mixed phenotype acute leukemia:a study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria[J].Am J Clin Pathol,2014,142(6):803-808.
[13]Bachir F,Zerrouk J,Howard SC,et al.Outcomes in patients w ith mixed phenotype acute leukemia in M orocco[J].J Pediatr Hematol Oncol,2014,36(6):392-397.
[14]Lee JH,Min YH,Chung CW,et al.Prognostic implications of the immunophenotype in biphenotypic acute leukemia[J].Leukemia&Lymphoma,2008,49(4):700-709.
[15]Yan L,Ping N,Zhu M,et al.Clinical,immunophenotypic,cytogenetic,and molecular genetic features in 117adult patients w ith mixed-phenotype acute leukemia defined by WHO-2008 classification[J].Haematologica,2012,97(11):1708-1712.
[16]Atfy M,Al Azizi NM,Elnaggar AM,et al.Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients:And its role in their outcome[J].Leuk Res,2011,35(10):1339-1344.
[17]赵林艳,周结,龚芳,等.异基因造血干细胞移植治疗16例混合表型急性白血病患者临床疗效观察[J].中华血液学杂志,2015,36(11):963-965.ZHAO Linyan,ZHOU Jie,GONG Fang,et al.Clinical efficacy observation of allogeneic hematopoietic stem cell transplantation in 16 patients w ith mixed phenotype acute leukemia[J].Chin Hematol,2015,36(11):963-965.
[18]Xu XQ,Wang JM,Lu SQ,et al.Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison w ith that of acute myeloidleukemia and acute lymphoblastic leukemia:a case series of a Chinese population[J].Haematologica,2009,94(7):919-927.
[19]Eckstein OS,Wang L,Punia JN,et al.Mixed-phenotype acute leukemia(M PAL)exhibits frequent mutations in DNM T3A and activated signaling genes[J].Exp Hematol,2016,44(8):740-744.
[20]Weinberg OK,Arber DA.Mixed-phenotype acute leukemia:historical overview and a new definition[J].Leukemia,2010,24(11):1844-1851.
[21]Lee JY,Lee SM,Lee JY,et al.Mixed-phenotype acute leukemia treated w ith decitabine[J].Korean J Intern M ed,2016,31(2):406-408.
[22]Stone RM.Transplantation after remission in mixed phenotype acute leukemia:a good idea[J].Biol Blood M arrow Transplant,2016,22(6):971-972.
[23]颜灵芝,陈苏宁,平娜娜,等.15例成人Ph染色体和/或BCR-ABL阳性混合表型急性白血病的临床及实验室特征分析[J].中华实验血液学杂志,2013,21(5):1116-1120.YAN Lingzhi,CHEN Suning,PING Nana,et al.Clinical and laboratorial analysis for 15 adult cases of mixed phenotypic acute leukemia w ith Ph chromosome and/or positive BCR-ABL[J].Journal of Experimental Hematology,2013,21(5):1116-1120.
[24]Tian H,Xu Y,Liu L,et al.Comparison of outcomes in mixed phenotype acute leukemiapatients treated w ith chemotherapy and stem cell transplantation versus chemotherapy alone[J].Leuk Res,2016,45:40-46.
[25]Munker R,Brazauskas R,Wang HL,et al.Allogeneic hematopoietic cell transplantation for patients w ith mixed phenotype acute leukemia[J].Biol Blood M arrow Transplant,2016,22(6):1024-1029.