Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2022 Jul;97(7):865-876. doi: 10.1002/ajh.26557. Epub 2022 Apr 16.
Progress with intensive chemotherapy and supportive care measures has improved survival in newly diagnosed acute myeloid leukemia (AML). Predicting outcome helps in treatment decision making. We analyzed survival as the treatment endpoint in 3728 patients with newly diagnosed AML treated with intensive chemotherapy from 1980 to 2021. We divided the total study group (3:1 basis) into a training (n = 2790) and a validation group (n = 938). The associations between survival and 27 characteristics were investigated. In the training cohort, the multivariate analysis identified 12 consistent adverse prognostic variables independently associated with worse survival: older age, therapy-related myeloid neoplasm, worse performance status, cardiac comorbidity, leukocytosis, anemia, thrombocytopenia, elevated creatinine and lactate dehydrogenase, cytogenetic abnormalities, and the presence of infection at diagnosis except fever of unknown origin. We categorized patients into four prognostic groups, favorable (7%), intermediate (43%), poor (39%), and very poor (11%) with estimated 5-year survival rates of 69%, 36%, 13%, and 3% respectively (p < .001). The predictive model was validated in an independent cohort. In a subset of patients with molecular mutation profiles, adding the mutation profiles after accounting for the effects of previous factors identified NPM1 (favorable), PTPN11, and TP53 (both unfavorable) mutations as molecular prognostic factors. The new proposed predictive model for survival with intensive chemotherapy in patients with AML is robust and can be used to advise patients regarding their prognosis, to modify therapy in remission (e.g., proposing allogeneic stem cell transplantation in first remission), and to compare outcome and benefits on future investigational therapies.
强化化疗和支持性护理措施的进展改善了新诊断的急性髓系白血病(AML)患者的生存。预测预后有助于治疗决策。我们分析了 3728 例新诊断的 AML 患者在 1980 年至 2021 年期间接受强化化疗的生存情况作为治疗终点。我们将总研究组(按 3:1 的比例)分为训练组(n=2790)和验证组(n=938)。研究了生存与 27 个特征之间的关系。在训练队列中,多变量分析确定了 12 个一致的不良预后变量,这些变量独立地与生存不良相关:年龄较大、治疗相关髓系肿瘤、较差的体能状态、心脏合并症、白细胞增多、贫血、血小板减少、肌酐和乳酸脱氢酶升高、细胞遗传学异常以及诊断时除发热原因不明外存在感染。我们将患者分为四个预后组,预后良好(7%)、中等(43%)、差(39%)和极差(11%),估计 5 年生存率分别为 69%、36%、13%和 3%(p<0.001)。该预测模型在独立队列中得到验证。在具有分子突变谱的患者亚组中,在考虑到先前因素的影响后添加突变谱,确定 NPM1(预后良好)、PTPN11 和 TP53(均预后不良)突变作为分子预后因素。新提出的 AML 患者强化化疗生存预测模型稳健可靠,可用于向患者提供预后建议,在缓解期修改治疗(例如,在首次缓解期建议进行异基因干细胞移植),并比较未来研究性治疗的结果和获益。