Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children's Oncology Group
Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children's Oncology Group
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DOI：
10.1200/jco.18.00313
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发表时间：
2019-01-01
影响因子：
45.3
通讯作者：
Aplenc, Richard
中科院分区：
文献类型：
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作者：
Getz, Kelly D.;Sung, Lillian;Aplenc, Richard
目的小儿急性髓细胞白血病治疗后的迟发性心脏毒性可导致严重的发病率和死亡率。早发性心脏毒性对治疗结果的影响尚不清楚。因此，我们评估了早期心脏毒性事件的危险因素和心脏毒性对无事件生存期（EFS）和总生存期（OS）的影响。Methodsacetylcholesterol毒性是通过对1,022例儿童急性髓细胞白血病患者在儿童肿瘤组试验AAML 0531中治疗的随访过程中的不良事件监测确定的。它被定义为2级或更高的左心室收缩功能障碍的基础上的共同术语标准不良事件（第3版）definitions. ResultsAbout 12%的患者经历了心脏毒性超过5年的随访，超过70%的事件发生在协议治疗。在按方案治疗期间记录的心脏毒性与随后的方案外毒性显著相关。总的来说，非婴儿和黑人患者的发病率较高，并且在血液感染的情况下。在有心脏毒性记录的患者中，EFS（风险比[HR]，1.6; 95% CI，1.2 - 2.1; P = 0.004）和OS（HR，1.6; 95% CI，1.2 - 2.2，P = 0.005）均显著更差。与无记录心脏毒性的患者相比，无论是在无感染（HR，1.6; 95% CI，1.1至2.2; P = 0.017）还是存在感染（HR，1.6; 95% CI，1.0至2.7; P = 0.069）的情况下发生心脏毒性事件，对EFS的影响均相同。然而，与感染无关的心脏毒性的OS降低更为明显（HR，1.7; 95% CI，1.2 - 2.5; P = .004）（HR，1.3; 95% CI，0.7 - 2.4; P = .387）.结论早期治疗-相关的心脏毒性可能与EFS和OS降低有关。和长期死亡率结果。
PurposeLate cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS).MethodsCardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children's Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions.ResultsApproximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387).ConclusionEarly treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.