Importance  To our knowledge, this multicenter analysis is the first to test and validate (1) the prognostic impact of comorbidities on 1-year mortality after initial therapy of acute myeloid leukemia (AML) and (2) a novel, risk-stratifying composite model incorporating comorbidities, age, and cytogenetic and molecular risks.

Objective  To accurately estimate risks of mortality by developing and validating a composite model that combines the most significant patient-specific and AML-specific features.

Design, Setting, and Participants  This is a retrospective cohort study. A series of comorbidities, including those already incorporated into the hematopoietic cell transplantation–comorbidity index (HCT-CI), were evaluated. Patients were randomly divided into a training set (n = 733) and a validation set (n = 367). In the training set, covariates associated with 1-year overall mortality at a significance level of P < .10 constructed a multivariate Cox proportional hazards model in which the impact of each covariate was adjusted for that of all others. Then, the adjusted hazard ratios were used as weights. Performances of models were compared using C statistics for continuous outcomes and area under the curve (AUC) for binary outcomes.

Exposures  Initial therapy for AML.

Main Outcomes and Measures  Death within 1 year after initial therapy for AML.

Results  A total of 1100 patients, ages 20 to 89 years, were treated for AML between January 1, 2008, and December 31, 2012, at 5 academic institutions specialized in treating AML; 605 (55%) were male, and 495 (45%) were female. In the validation set, the original HCT-CI had better C statistic and AUC estimates compared with the AML comorbidity index for prediction of 1-year mortality. Augmenting the original HCT-CI with 3 independently significant comorbidities, hypoalbuminemia, thrombocytopenia, and high lactate dehydrogenase level, yielded a better C statistic of 0.66 and AUC of 0.69 for 1-year mortality. A composite model comprising augmented HCT-CI, age, and cytogenetic/molecular risks had even better predictive estimates of 0.72 and 0.76, respectively.

Conclusions and Relevance  In this cohort study, comorbidities influenced 1-year survival of patients with AML, and comorbidities are best captured by an augmented HCT-CI. The augmented HCT-CI, age, and cytogenetic/molecular risks could be combined into an AML composite model that could guide treatment decision-making and trial design in AML. Studying physical, cognitive, and social health might further clarify the prognostic role of aging. Targeting comorbidities with interventions alongside specific AML therapy might improve survival.

重要性  据我们所知，这项多中心分析首次测试和验证了 (1) 合并症对急性髓系白血病 (AML) 初始治疗后 1 年死亡率的预后影响和 (2) 一种新型的风险分层复合模型包括合并症、年龄、细胞遗传学和分子风险。

目的  通过开发和验证结合最重要的患者特异性和 AML 特异性特征的复合模型来准确估计死亡风险。

设计、设置和参与者  这是一项回顾性队列研究。评估了一系列合并症，包括那些已经纳入造血细胞移植合并症指数 (HCT-CI) 的合并症。患者被随机分为训练集（n = 733）和验证集（n = 367）。在训练集中，与 1 年总体死亡率相关的协变量在P  < .10的显着性水平上构建了一个多变量 Cox 比例风险模型，其中每个协变量的影响针对所有其他协变量的影响进行了调整。然后，将调整后的风险比用作权重。使用连续结果的 C 统计量和二元结果的曲线下面积 (AUC) 比较模型的性能。

暴露  AML 的初始治疗。

主要结果和措施  AML 初始治疗后 1 年内死亡。

结果  2008年1月1日至2012年12月31日，在5个专门治疗AML的学术机构共收治了1100名年龄在20～89岁之间的AML患者；605 (55%) 名男性，495 (45%) 名女性。在验证集中，与 AML 合并症指数相比，原始 HCT-CI 具有更好的 C 统计量和 AUC 估计值，用于预测 1 年死亡率。用 3 种独立显着的合并症、低白蛋白血症、血小板减少症和高乳酸脱氢酶水平增加原始 HCT-CI，产生了更好的 C 统计量 0.66 和 0.69 的 1 年死亡率的 AUC。包含增强 HCT-CI、年龄和细胞遗传学/分子风险的复合模型分别具有更好的预测估计值 0.72 和 0.76。

结论和相关性  在这项队列研究中，合并症影响了 AML 患者的 1 年生存率，并且合并症最好通过增强的 HCT-CI 来捕捉。增强的 HCT-CI、年龄和细胞遗传学/分子风险可以组合成一个 AML 复合模型，可以指导 AML 的治疗决策和试验设计。研究身体、认知和社会健康可能会进一步阐明衰老的预后作用。在特定 AML 治疗的同时，针对合并症进行干预可能会提高生存率。