Divisions of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Am J Hematol. 2022 Sep;97(9):1127-1134. doi: 10.1002/ajh.26630. Epub 2022 Jun 30.
The current study was approached with the assumption that response to induction chemotherapy, in acute myeloid leukemia (AML), overshadows pre-treatment risk variables in predicting survival and therefore be used as an anchor for a simplified risk model. We considered 759 intensively-treated patients with AML, not promyelocytic: median age 60 years; primary 66%, secondary 25%, and therapy-related 9%; European LeukemiaNet cytogenetic risk category favorable 8%, intermediate 61%, and adverse 31%. Complete remission with (CR) or without (CRi) count recovery was achieved in 608 (80%) patients. After a median follow-up of 22 months, 503 deaths, 272 relapses, and 257 allogeneic hematopoietic stem cell transplants (AHSCTs) were recorded. Multivariable analysis identified failure to achieve CR/CRi (HR 3.8, 95% CI 3.1-4.8), adverse karyotype (2.2, 1.8-2.8), and age >55 years (2.1, 1.6-2.7) as main risk factors for survival. HR-weighted scoring resulted in four-tiered risk stratification: low (0 points; N = 183), intermediate-1 (1 point; N = 331), intermediate-2 (2 points; N = 117), and high (≥3 points; N = 128), with respective median survival (5-year rate) not reached (68%), 34 (37%), 13 (20%), and 5 (5%) months (p < .001). FLT3-ITD mutation was associated with inferior survival in intermediate-1 (p = .004) and TP53 in intermediate-2 (p = .06) and high (p = .02) risk disease; the latter was fully accounted for by the close association between TP53 mutation and complex/monosomal karyotype while the observations regarding FLT3-ITD were not affected by treatment with midostaurin. AHSCT had a favorable impact on survival, most apparent in intermediate-1 (p < .001), intermediate-2 (p = .03), and high (p = .01) risk disease. The proposed 3-factor survival model offers a novel prototype that is amenable to further enhancement by molecular information and was validated in an external cohort of 1032 intensively-treated AML patients.
本研究假设急性髓系白血病（AML）对诱导化疗的反应比治疗前的风险因素更能预测生存，因此可作为简化风险模型的锚定点。我们考虑了 759 名接受强化治疗的非早幼粒细胞性 AML 患者：中位年龄 60 岁；原发性 66%，继发性 25%，治疗相关性 9%；欧洲白血病网细胞遗传学风险类别为有利 8%，中等 61%，不良 31%。608 例（80%）患者达到完全缓解（CR）或不完全缓解伴计数恢复（CRi）。中位随访 22 个月后，记录了 503 例死亡、272 例复发和 257 例异基因造血干细胞移植（AHSCT）。多变量分析确定未达到 CR/CRi（HR 3.8，95%CI 3.1-4.8）、不良核型（2.2，1.8-2.8）和年龄>55 岁（2.1，1.6-2.7）是生存的主要危险因素。HR 加权评分导致了四层次风险分层：低危（0 分；N=183）、中危-1（1 分；N=331）、中危-2（2 分；N=117）和高危（≥3 分；N=128），中位生存（5 年率）分别为未达到（68%）、34（37%）、13（20%）和 5（5%）个月（p<0.001）。FLT3-ITD 突变与中危-1（p=0.004）和中危-2（p=0.06）和高危（p=0.02）疾病的生存不良相关；在高危疾病中，TP53 突变与复杂/单体核型密切相关，这完全解释了 TP53 突变的观察结果，而关于 FLT3-ITD 的观察结果不受米哚妥林治疗的影响。AHSCT 对生存有有利影响，在中危-1（p<0.001）、中危-2（p=0.03）和高危（p=0.01）疾病中最为明显。提出的 3 因素生存模型提供了一个新的原型，通过分子信息进一步增强是可行的，并在 1032 名接受强化治疗的 AML 患者的外部队列中得到验证。
