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C. Caprioli et al.
rent abnormalities;1 ii) sAML: patients with a documented clini- cal history of MDS, MDS/MPN or MPN and/or cytogenetic WHO criteria of AML with MDS-related changes;1 iii) de novo AML: none of the above. In order to avoid any ambiguous inter- pretation, morphological WHO criteria of AML with MDS-relat- ed changes were not considered in the definition of sAML. Patients with MDS, therapy-related AML or not provided with a cytogenetic and/or molecular characterization were excluded from the analysis.
Statistical analysis
The clinical endpoints of the study were defined according to standard criteria.19 Comparisons between baseline characteris- tics and AML categories were analyzed using the Mann- Whitney U test for countinuous and Chi-squared or Fisher’s exact test for categorical variables. Overall survival (OS) and dis- ease-free survival (DFS) were estimated by the Kaplan-Meier method and any differences between AML categories or consol- idation treatment were evaluated with log-rank test. Cox mod- els were used to estimate hazard ratios (HR) with 95% Confidence Intervals (CI) in univariate and multivariable analy- sis on survival outcomes. AlloHSCT was considered as a time-
dependent event; outcome data were estimated by the Mantel- Byar method and graphically illustrated by Simon-Makuch plots. All reported P-values are two-sided and set at 5% signifi- cance level. All analyses were performed with R software, ver- sion 3.5.0.
Results
Characteristics of patients
Among 574 adult patients enrolled in the NILG-AML 02/06 trial,16 413 (72%) with full genetic characterization resulted evaluable and were classified as 55 CS-AML patients, 100 sAML patients (28 defined by clinical histo- ry, of which 24 after MDS or MDS/MPN and four after MPN, and 72 defined by cytogenetic criteria) and 258 de novo AML patients (Figure 1). The 55 cases reclassified as CS-AML represented 17.6% of otherwise defined de novo AML patients and 13% of the whole analyzed cohort.
The main clinical characteristics of patients are report- ed in Table 1. Compared to de novo AML, patients with sAML and CS-AML were similarly older (median age 48,
Figure 1. CONSORT diagram illustrating patient selection. ICE: idarubicin, cytarabine, etoposide; sHD: sequential high-dose chemotherapy; TKI: tyrosine-kinase inhibitors; AML: acute myeloid leukemia; tAML: therapy-related AML; sAML: secondary AML; CS-AML: de novo AML carrying chromatin-spliceosome mutations; MDS: myelodysplastic syndrome; WHO: World Health Orginization; NGS: next-generation squencing.
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