急性髓系白血病患者完全缓解后CD45_(dim)CD117~+细胞检测的预后意义
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摘要
目的:探索成人急性髓系白血病(AML)获得第一次完全缓解(CR1)后2周内CD45_(dim)CD117~+表型细胞对复发、预后的预测价值。方法:回顾性分析2014年7月1日至2017年6月30日诱导治疗的初诊AML(非急性早幼粒细胞白血病)治疗资料,解析初诊时临床特征、CR1后2周内CD45_(dim)CD117~+表型细胞与预后的关系。结果:检测CD45_(dim)CD117~+表型细胞的患者共91例,初诊时年龄中位数为51岁,WBC中位数为11.60×10~9/L,骨髓原始细胞比例中位数0.35。按照FAB分型,M_0 1例(1.1%),M1 7例(7.7%),M2 38例(41.7%),M_4 20例(22.0%),M5 21例(23.1%),M6 4例(4.4%)。按NCCN危险度分组,预后良好30例(33.0%),预后中等51例(56.0%),预后不良10例(11.0%)。CR1后2周内CD45_(dim)CD117~+表型细胞比例中位数1.8500(0.0236-8.0000)%。中位随访时间为473(64-1454)d,自开始诱导治疗至获得CR的中位时间为46 d,中位RFS时间为319 d,中位OS时间为352 d。复发45例,其中14例死亡;46例未复发,其中3例死亡。根据受试者工作特征曲线(ROC)得到CD45_(dim)CD117~+表型细胞比例的阈值为2.055%(Se=0.733,Sp=0.761),CD45_(dim)CD117~+表型细胞>2.055%者44例,中位数为3.075%,复发33例,死亡12例;CD45_(dim)CD117~+表型细胞比例<2.055%者47例,中位数为1.150%,复发12例,死亡5例。回归分析结果显示,WBC计数>50×10~9/L、CD45_(dim)CD117~+表型细胞比例> 2.055%是复发的独立危险因素。CD45_(dim)CD117~+表型细胞比例>2.055%组2年RFS率为54.3%,2年OS率为52.8%;CD45_(dim)CD117~+表型细胞比例<2.055%组2年RFS率为86.6%(P=0.018),2年OS率为85.3%(P=0.033)。结论:对于成人AML患者,CR1后2周内CD45_(dim)CD117~+表型细胞比例> 2.055%是复发的独立危险因素,也是RFS和OS的不利因素。
Objective: To investigate the predictive value of CD45_(dim)CD117~+ phenotype-abnormal cells(hereinafter referred to as "abnormal cells")for relapse and prognosis in adult patients with acute myeloid leukemia(AML) within2 weeks after the first complete remission(CR1). Methods: The clinical data of patients with newly diagnosed AML(non-acute promyelocytic leukemia) admitted in our department from July 1, 2014 to June 30, 2017 were analyzed retrospectively, and the relationship between clinical features at the initial diagnosis and the abnormal phenotype cells of CD45_(dim)CD117~+ within 2 weeks after CR1 with the prognosis were analyzed. Results: A total of 91 patients with CD45_(dim)CD117~+ abnormal cells were detected. The median age was 51 years old, the median WBC count was 11.60 x 109/L, and the median ratio of bone marrow blast cells was 0.35 at initial diagnosis. According to the FAB classification,1(1.1%), 7(7.7%), 38(41.7%), 20(22.0%), 21(23.1%) and 4(4.4%) patients were classifice as M_0, M_1, M_2, M_4, M_5,and M_6, respectively. According to the NCCN risk stratification, 30(33.0%), 51(56.0%), and 10(11.0%) patients were determined as good, moderate, and poor prognosis, respectively. The median ratio of abnormal cells within 2 weeks after CR1 was 1.8500(0.0236-8.0000)%. The median time from initiation of induction therapy to the acquisition of CR was46 days, median recurrence-free survival time was 319 days, and median overall survival time was 352 days. A total of 45 patients relapsed, of which 14 died; 46 patients did not relapse, of which 3 died. The cutoff of abnormal cells by receiver operating characteristic curve(ROC) analysis was 2.055%(Se = 0.733,Sp = 0.761). The abnormal cell ratio was > 2.055%in 44 patients, the median ratio of abnormal cells was 3.075%, among which 33 patients relapsed and 12 patients died;the abnormal cell ratio was < 2.055% in 47 patients, the median ratio of abnormal cells was 1.150%, 12 patients relapsed and 5 patients died. Regression analysis showed that WBC count > 50 × 10~9/L and abnormal cell ratio >2.055% were independent risk factors for recurrence. The abnormal cell ratio > 2.055% group had a 2-year RFS rate of 54.3% and a2-year OS rate of 52.8%. The abnormal cell ratio < 2.055% group had a 2-year RFS rate of 86.6%(P=0.018), and a 2-year OS rate of 85.3%(P < 0.05). Conclusion: For adult AML patients, CD45_(dim)CD117~+ phenotypical abnormal cells ratio >2.055% within 2 weeks after CR1 is an independent risk factor for recurrence, which also is an dverse factor for RFS and OS.
Objective: To investigate the predictive value of CD45_(dim)CD117~+ phenotype-abnormal cells(hereinafter referred to as "abnormal cells")for relapse and prognosis in adult patients with acute myeloid leukemia(AML) within2 weeks after the first complete remission(CR1). Methods: The clinical data of patients with newly diagnosed AML(non-acute promyelocytic leukemia) admitted in our department from July 1, 2014 to June 30, 2017 were analyzed retrospectively, and the relationship between clinical features at the initial diagnosis and the abnormal phenotype cells of CD45_(dim)CD117~+ within 2 weeks after CR1 with the prognosis were analyzed. Results: A total of 91 patients with CD45_(dim)CD117~+ abnormal cells were detected. The median age was 51 years old, the median WBC count was 11.60 x 109/L, and the median ratio of bone marrow blast cells was 0.35 at initial diagnosis. According to the FAB classification,1(1.1%), 7(7.7%), 38(41.7%), 20(22.0%), 21(23.1%) and 4(4.4%) patients were classifice as M_0, M_1, M_2, M_4, M_5,and M_6, respectively. According to the NCCN risk stratification, 30(33.0%), 51(56.0%), and 10(11.0%) patients were determined as good, moderate, and poor prognosis, respectively. The median ratio of abnormal cells within 2 weeks after CR1 was 1.8500(0.0236-8.0000)%. The median time from initiation of induction therapy to the acquisition of CR was46 days, median recurrence-free survival time was 319 days, and median overall survival time was 352 days. A total of 45 patients relapsed, of which 14 died; 46 patients did not relapse, of which 3 died. The cutoff of abnormal cells by receiver operating characteristic curve(ROC) analysis was 2.055%(Se = 0.733,Sp = 0.761). The abnormal cell ratio was > 2.055%in 44 patients, the median ratio of abnormal cells was 3.075%, among which 33 patients relapsed and 12 patients died;the abnormal cell ratio was < 2.055% in 47 patients, the median ratio of abnormal cells was 1.150%, 12 patients relapsed and 5 patients died. Regression analysis showed that WBC count > 50 × 10~9/L and abnormal cell ratio >2.055% were independent risk factors for recurrence. The abnormal cell ratio > 2.055% group had a 2-year RFS rate of 54.3% and a2-year OS rate of 52.8%. The abnormal cell ratio < 2.055% group had a 2-year RFS rate of 86.6%(P=0.018), and a 2-year OS rate of 85.3%(P < 0.05). Conclusion: For adult AML patients, CD45_(dim)CD117~+ phenotypical abnormal cells ratio >2.055% within 2 weeks after CR1 is an independent risk factor for recurrence, which also is an dverse factor for RFS and OS.
引文
1 Baer MR,Stewart CC,Dodge RK,et al.High frequency of immunophenotype changes in acute myeloid leukemia at relapse:implications for residual disease detection(Cancer and Leukemia Group B Study 8361).Blood,2001;97(11):3574-3580.
2 Swerdlow SH,Campo E,Harris NL,et al.WHO classification of tumours of heamatopoietic and lymphoid tissues.4th ed.Lyon:IARC Press.2008:110-147.
3 NCCN Clinical Practice Guidelines in Oncology(NCCNGuidelines?).Acute Myeloid Leukemia(Version 1.2015).http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf.
4 Mi Y,Xue Y,Yu W,et al.Therapeutic experience of adult acute myeloid leukemia in a single institution of China and its relationship with chromosome karyotype.Leuk Lymphoma,2008;49(3):524-530.
5张之南,沈悌血液病诊断及疗效标准第3版.北京:科学出版社,2007:106-131.
6 Cheson BD,Bennett JM,Kopecky KJ,et al.Revised recommendations of the International Working Group for Diagnosis,Standardization of Response Criteria,Treatment Outcomes,and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.J Clin Oncol,2003;21(24):4642-4649.
7刘艳荣,王亚哲,陈珊珊,等.610例急性髓系白血病免疫表型和白血病相关免疫表型分析.中华血液学杂志,2007;28(11):731-736.
8 Pomerantz A,Rodriguez-Rodriguez S,Demichelis-Gomez R,et al.Importance of CD117 in the assignation of a myeloid lineage in acute leukemias.Arch Med Res,2017;48(2):212-215.
9 Kohnke T,Sauter D,Ringel K,et al.Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse.Leukemia,2015;29(2):377-386.
10 Maurillo L,Buccisano F,Del Principe MI,et al.Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia.J Clin Oncol,2008;26(30):4944-4951.
11 Ravandi F,Jorgensen J,Borthakur G,et al.Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia.Cancer,2017;123(3):426-435.
12 Chen X,Xie H,Wood BL,et al.Relation of clinical response and minimal residual disease and their prognostic impact on outcome in acute myeloid leukemia.J Clin Oncol,2015;33(11):1258-1264.
13 Desbourdes L,Javary J,Charbonnier T,et al.Alteration analysis of bone marrow mesenchymal stromal cells from De Novo acute myeloid leukemia patients at diagnosis.Stem Cells Dev,2017;26(10):709-722.
14彭楠,魏辉,林冬,等.急性髓系白血病患者诱导化疗后第七或第八天微小残留病检测的预后意义.中华血液学杂志,2017;38(9):767-771.
15 Al-Mawali A,Gillis D,Lewis I.The use of receiver operating characteristic analysis for detection of minimal residual disease using five-color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse.Cytometry BClin Cytom,2009;76(2):91-101.
16 Buccisano F,Maurillo L,Gattei V,et al.The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia.Leukemia,2006;20(10):1783-1789.
17孙楠楠,甘思林,孙慧,等.流式细胞术动态监测急性白血病完全缓解后微小残留病与预后的关系.中国实验血液学杂志,2013;21(2):339-342.
18 Hoehn D,Medeiros LJ,Chen SS,et al.CD117 expression is a sensitive but nonspecific predictor of FLT3 mutation in T acute lymphoblastic leukemia and T/myeloid acute leukemia.Am J Clin Pathol,2012;137(2):213-219.
2 Swerdlow SH,Campo E,Harris NL,et al.WHO classification of tumours of heamatopoietic and lymphoid tissues.4th ed.Lyon:IARC Press.2008:110-147.
3 NCCN Clinical Practice Guidelines in Oncology(NCCNGuidelines?).Acute Myeloid Leukemia(Version 1.2015).http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf.
4 Mi Y,Xue Y,Yu W,et al.Therapeutic experience of adult acute myeloid leukemia in a single institution of China and its relationship with chromosome karyotype.Leuk Lymphoma,2008;49(3):524-530.
5张之南,沈悌血液病诊断及疗效标准第3版.北京:科学出版社,2007:106-131.
6 Cheson BD,Bennett JM,Kopecky KJ,et al.Revised recommendations of the International Working Group for Diagnosis,Standardization of Response Criteria,Treatment Outcomes,and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.J Clin Oncol,2003;21(24):4642-4649.
7刘艳荣,王亚哲,陈珊珊,等.610例急性髓系白血病免疫表型和白血病相关免疫表型分析.中华血液学杂志,2007;28(11):731-736.
8 Pomerantz A,Rodriguez-Rodriguez S,Demichelis-Gomez R,et al.Importance of CD117 in the assignation of a myeloid lineage in acute leukemias.Arch Med Res,2017;48(2):212-215.
9 Kohnke T,Sauter D,Ringel K,et al.Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse.Leukemia,2015;29(2):377-386.
10 Maurillo L,Buccisano F,Del Principe MI,et al.Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia.J Clin Oncol,2008;26(30):4944-4951.
11 Ravandi F,Jorgensen J,Borthakur G,et al.Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia.Cancer,2017;123(3):426-435.
12 Chen X,Xie H,Wood BL,et al.Relation of clinical response and minimal residual disease and their prognostic impact on outcome in acute myeloid leukemia.J Clin Oncol,2015;33(11):1258-1264.
13 Desbourdes L,Javary J,Charbonnier T,et al.Alteration analysis of bone marrow mesenchymal stromal cells from De Novo acute myeloid leukemia patients at diagnosis.Stem Cells Dev,2017;26(10):709-722.
14彭楠,魏辉,林冬,等.急性髓系白血病患者诱导化疗后第七或第八天微小残留病检测的预后意义.中华血液学杂志,2017;38(9):767-771.
15 Al-Mawali A,Gillis D,Lewis I.The use of receiver operating characteristic analysis for detection of minimal residual disease using five-color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse.Cytometry BClin Cytom,2009;76(2):91-101.
16 Buccisano F,Maurillo L,Gattei V,et al.The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia.Leukemia,2006;20(10):1783-1789.
17孙楠楠,甘思林,孙慧,等.流式细胞术动态监测急性白血病完全缓解后微小残留病与预后的关系.中国实验血液学杂志,2013;21(2):339-342.
18 Hoehn D,Medeiros LJ,Chen SS,et al.CD117 expression is a sensitive but nonspecific predictor of FLT3 mutation in T acute lymphoblastic leukemia and T/myeloid acute leukemia.Am J Clin Pathol,2012;137(2):213-219.
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