获得性再生障碍性贫血恶性克隆性演变的长期随访研究

目的 观察获得性再生障碍性贫血(AA)治疗后演变为骨髓增生异常综合征(MDS)和(或)急性髓系白血病(AML)的发生率并分析其危险因素.方法 长期随访1991至2009年收治的1003例从患者,观察疾病演变,并分析其进展为MDS/AML的可能危险因素,包括患者性别、年龄、病因、治疗前后染色体核型变迁、疾病严重程度、治疗方案及治疗反应等.结果 1003例患者中位随访时间为62(2～423)个月,其5年总生存率为(78.0±1.0)%,共计27例转化为MDS/AML[非重型AA(NSAA)11例,重型AA(SAA)6例,超重型AA(VSAA)10例].Kaplan-Meier估计法分析1003例AA患者10年MDS/AML转化率为(4.5 ±1.0)%,VSAA组10年MDS/AML转化率[(12.8±3.5)%]显著高于NSAA组[(4.1±1.9)%,P＜0.01]和SAA组[(3.5±1.4)%,P＜0.01],而后二组间差异无统计学意义(P=0.616).单因素及多因素分析均显示患者年龄＞40岁[RR=3.527(95%CI:1.598～7.784),P＜0.01]、VSAA[RR=5.122(95%CI:2.214～11.853),P＜0.01]、发病前射线、毒物、化学制剂等接触史[RR=3.401(95%CI:1.535～7.534),P＜0.01]及重组人粒细胞集落刺激因子(rhuGCSF)疗程大于300 d[RR=10.782(95%CI:4.600～25.269),P＜0.01]为AA转化为MDS/AML的危险因素.结论 长期随访对于评估AA患者治疗后进展为MDS/AML至关重要,随访期间应制定规范监测策略,及时发现转化的MDS/AML并尽早采取相应措施阻断其进展.

Abstract：

Objective To assess the incidence and risk factors for evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).Method A total of 1003 AA patients hospitalized in our institute hospital between January 1991 and December 2009 enrolled into this study.The incidence and risk factors for AA developing MDS/AML by the Kaplan-Meier method and Cox proportional hazards models, respectively.Results The median follow-up was 62(2 -423) months and the projected 5-year survival rate was (78.0 ± 1.0) %.Twenty-seven patients evolved to MDS/AML, of whom 11,6 and 10 were from NSAA, SAA and VSAA subgroups, respectively.The estimated cumulative incidence of MDS/AML transformation for these 1003 patients after diagnosis was (4.5 ± 1.0)% at 10 year.The incidence of MDS/AML transformation in VSAA subgroup[(12.8 ±3.5)%]was significantly higher than in NSAA subgroup[(4.1 ±1.9)%](P＜0.001) and SAA subgroup[(3.5 ± 1.4)%](P = 0.008) ,but no difference between the latter two subgroups (P = 0.616).Age[RR=3.527 (95%CI:1.598 -7.784) ,P = 0.002], severity of disease[RR=5.122 (95%CI:2.214 - 11.853) ,P ＜0.001], the duration (days) of rhuG-CSF therapy[RR = 10.782 (95%CI:4.600-25.269) ,P＜0.001]and exposure to ray, chemicals or drugs[RR = 3.401 (95% CI: 1.535 -7.534) ,P = 0.003]were risk factors for the transformation in both univariate and multivariate analyses.Conclusion Long-term follow-up is essential to assess the incidence and risk factors for evolutions of acquired AA into MDS/AML, and to administer salvage therapy for transformation in time during follow-up.

Long-term follow-up of malignant clonal evolution in patients with acquired aplastic anemia

Objective To assess the incidence and risk factors for evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).Method A total of 1003 AA patients hospitalized in our institute hospital between January 1991 and December 2009 enrolled into this study.The incidence and risk factors for AA developing MDS/AML by the Kaplan-Meier method and Cox proportional hazards models, respectively.Results The median follow-up was 62(2 -423) months and the projected 5-year survival rate was (78.0 ± 1.0) %.Twenty-seven patients evolved to MDS/AML, of whom 11,6 and 10 were from NSAA, SAA and VSAA subgroups, respectively.The estimated cumulative incidence of MDS/AML transformation for these 1003 patients after diagnosis was (4.5 ± 1.0)% at 10 year.The incidence of MDS/AML transformation in VSAA subgroup[(12.8 ±3.5)%]was significantly higher than in NSAA subgroup[(4.1 ±1.9)%](P＜0.001) and SAA subgroup[(3.5 ± 1.4)%](P = 0.008) ,but no difference between the latter two subgroups (P = 0.616).Age[RR=3.527 (95%CI:1.598 -7.784) ,P = 0.002], severity of disease[RR=5.122 (95%CI:2.214 - 11.853) ,P ＜0.001], the duration (days) of rhuG-CSF therapy[RR = 10.782 (95%CI:4.600-25.269) ,P＜0.001]and exposure to ray, chemicals or drugs[RR = 3.401 (95% CI: 1.535 -7.534) ,P = 0.003]were risk factors for the transformation in both univariate and multivariate analyses.Conclusion Long-term follow-up is essential to assess the incidence and risk factors for evolutions of acquired AA into MDS/AML, and to administer salvage therapy for transformation in time during follow-up.