原发肿瘤进展至急性髓系白血病不同时间间隔患者临床特征及化疗效果观察

Clinical characteristics of patients with acute myeloid leukemia transformed from primary tumors at different time intervals and chemotherapy efficacy

目的观察不同原发肿瘤进展至急性髓系白血病(AML)的时间,探讨原发肿瘤进展至AML不同时间间隔患者的临床特征及预后差异。方法2014年1月-2021年12月河南省肿瘤医院诊治继发性AML患者75例,根据原发肿瘤进展至AML的中位时间(19个月)分为短间隔组(<19个月)37例和长间隔组(≥19个月)38例。比较2组原发肿瘤类型,AML类型,染色体异常、PML-RARA融合基因阳性、基因突变比率及入院时白细胞计数、血小板计数、乳酸脱氢酶水平、骨髓原始细胞比例等临床资料;采用多因素logistic回归分析原发肿瘤进展至AML时间间隔较短的影响因素。11例患者确诊AML后放弃治疗(短间隔组4例,长间隔组7例),余患者根据AML FAB分型给予标准方案化疗,第1个疗程结束后评估疗效,未达完全缓解(CR)或形态学完全缓解而血细胞计数未完全恢复(CRi)者再化疗1个疗程。比较2组化疗1~2个疗程后CR、CRi、部分缓解(PR)及未缓解率。随访至2022年3月,比较2组总生存期及化疗1~2个疗程后达CR+CRi患者无复发生存期。结果短间隔组实体瘤比率(18.9%)、PML-RARA融合基因阳性率(10.8%)及入院时血红蛋白水平[71.0(64.5,78.0)g/L]均低于长间隔组[44.7%、39.5%、80.5(67.8,93.8)g/L](P<0.05),骨髓增生异常综合征(MDS)进展至AML比率(67.6%)高于长间隔组(26.3%)(χ^(2)=12.818,P<0.001),年龄、白细胞计数、血小板计数、乳酸脱氢酶水平、骨髓原始细胞比例及男性、染色体异常、基因突变比率与长间隔组比较差异均无统计学意义(P>0.05)。MDS进展至AML(OR=5.833,95%CI:2.151~15.818,P=0.001)是原发肿瘤进展至AML时间间隔较短的影响因素。短间隔组CR、CRi、PR、未缓解率(36.4%、33.3%、9.1%、21.2%)与长间隔组(45.2%、12.9%、16.1%、25.8%)比较差异均无统计学意义(P>0.05)。随访至2022年3月,短间隔组病死率(81.8%)高于长间隔组(48.4%)(χ^(2)=7.919,P=0.005),中位总生存期(7个月)、无复发生存期(3个月)均短于长间隔组(27、79个月)(χ^(2)=5.605,P=0.018;χ^(2)=10.514,P=0.001)。结论对继发性AML患者,原发肿瘤进展至AML时间间隔较长者化疗后总生存期和无复发生存期较长,MDS进展至AML的时间间隔较短。

Objective To observe the progression time of primary tumors to acute myeloid leukemia(AML),and to explore the clinical characteristics and prognosis of patients with AML from primary tumors at different time intervals.Methods From January 2014to December 2021,75patients with secondary AML were diagnosed and treated in Henan Cancer Hospital,and they were divided into 37patients with time interval of<19 months(short interval group)and 38patients with time interval of≥19months(long interval group)according to the median time interval from primary tumors to AML(19 months).The primary tumor type,secondary AML classification,rate of chromosome abnormality,PML-RARAfusion gene positive rate,gene mutation rate,and some laboratory indexes on admission as white blood cell count,platelet count,lactate dehydrogenase and bone marrow blast percentage were compared between two groups.Multivariate logistic regression analysis was performed to analyze the influencing factors of short time interval from primary tumors to AML.Eleven patients abandoned treatment after being diagnosed with AML,including 4patients in short interval group and 7patients in long interval group.The remaining patients were given conventional standard chemotherapy according to AML FAB classification,and the efficacy was evaluated after the first course.Those who did not achieve complete remission(CR)or CR with incomplete hematologic recovery(CRi)were given another course of chemotherapy.The CR,CRi,partial remission(PR)and no-remission rates were compared between two groups after1-or 2-course chemotherapy.The follow-up was conducted till March 2022,and the total survival time and relapse-free survival time of CR+CRi patients were compared between two groups.Results The rate of solid tumor,PML-RARA fusion gene positive rate and hemoglobin level on admission were higher in long interval group[44.7%,39.5%,80.5(67.8,93.8)g/L]than those in short interval group[18.9%,10.8%,71.0(64.5,78.0)g/L](P<0.05),the percentage of patients with AML from myelodysplastic syndrome was lower in long interval group(26.3%)than that in short interval group(67.6%)(χ^(2)=12.818,P<0.001),and there were no significant differences in the age,white blood cell count,bone marrow blast percentage,platelet count,lactate dehydrogenase level,male ratio,rate of chromosome abnormality and gene mutation rate between two groups(P>0.05).Progression to AML from myelodysplastic syndrome(OR=5.833,95%CI:2.151-15.818,P=0.001)was an influencing factor of short time interval from primary tumors to AML.There were no significant differences in CR,CRi,PR and no-remission rates between short interval group(36.4%,33.3%,9.1%,21.2%)and long interval group(45.2%,12.9%,16.1%,25.8%)(P>0.05).Till March2022,the mortality rate was higher in short interval group(81.8%)than that in long interval group(48.4%)(χ^(2)=7.919,P=0.005),and the median overall survival time and relapse-free survival time were shorter in short interval group(7,3 months)than those in long interval group(27,79 months)(χ^(2)=5.605,P=0.018;χ^(2)=10.514,P=0.001).Conclusion Patients with secondary AML from primary tumors at long time interval have long overall survival time and relapse-free survival time after chemotherapy,and a short time interval from myelodysplastic syndrome to AML.