DataSheet_1_Development of a Nomogram for Predicting the Cumulative Incidence of Disease Recurrence of AML After Allo-HSCT.doc

Using targeted exome sequencing, we studied correlations between mutations at diagnosis and transplant outcomes in 332 subjects with acute myeloid leukemia (AML) receiving allotransplantation. A total of 299 patients (299/332, 90.1%) had at least one oncogenic point mutation. In multivariable analyses, pretransplant disease status, minimal residual disease (MRD) before transplantation (pre-MRD), cytogenetic risk classification, and TP53 and FLT3-ITDhigh ratio mutations were independent risk factors for AML recurrence after allotransplantation (p < 0.05). A nomogram for the cumulative incidence of relapse (CIR) that integrated all the predictors in the multivariable model was then constructed, and the concordance index (C-index) values at 6, 12, 18, and 24 months for CIR prediction were 0.754, 0.730, 0.715, and 0.690, respectively. Moreover, calibration plots showed good agreements between the actual observation and the nomogram prediction for the 6, 12, 18, and 24 months posttransplantation CIR in the internal validation. The integrated calibration index (ICI) values were 0.008, 0.055, 0.094, and 0.136 at 6, 12, 18, and 24 months posttransplantation, respectively. With a median cutoff score of 9.73 from the nomogram, all patients could be divided into two groups, and the differences in 2-year CIR, disease-free survival (DFS), and overall survival (OS) between these two groups were significant (p < 0.05). Taken together, the results of our study indicate that gene mutations could help to predict the outcomes of patients with AML receiving allotransplantation.

采用针对性的外显子测序技术，本研究对332例接受异基因移植治疗的急性髓系白血病（AML）患者的诊断时突变与移植预后之间的相关性进行了探讨。其中，299名患者（占332例的90.1%）至少存在一种致癌性点突变。在多因素分析中，移植前疾病状态、移植前微小残留病（MRD）、细胞遗传学风险分类以及TP53和FLT3-ITDhigh比率突变被证实为异基因移植后AML复发的独立风险因素（p < 0.05）。随后，构建了一个综合多因素模型中所有预测因子的累积复发发生率（CIR）预测量表，并在6、12、18和24个月对CIR预测的符合指数（C-index）值分别为0.754、0.730、0.715和0.690。此外，校准图显示了内部验证中实际观察值与预测量表在6、12、18和24个月移植后CIR预测之间的良好一致性。在6、12、18和24个月移植后，综合校准指数（ICI）值分别为0.008、0.055、0.094和0.136。通过量表的中位数截止分数9.73，所有患者均可被分为两组，这两组在2年CIR、无病生存期（DFS）和总生存期（OS）方面的差异均显著（p < 0.05）。综合而言，本研究结果表明，基因突变有助于预测接受异基因移植的AML患者的预后。