Differential Induction Among Younger Patients Diagnosed with Secondary Acute Myelogenous Leukemia Is Feasible By Cytogenetic/Molecular Risk Stratification

Background: Secondary acute myeloid leukemia (s-AML) [therapy-related (t-AML) and evolving from antecedent hematologic disorder, i.e. myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN)] are highly aggressive disorders with 20% overall survival [OS] at 1 year. Challenges for initial therapy selection include 1. Difficulty for precise discrimination of pre-existing disorders [MDS vs MPN vs t-AML] and 2. Lack of reliable karyotypic/molecular risk stratification [i.e. European-leukemia-network-2017 [ELN 2017], originally designed for de novo AML]. In s-AML, enrichment for high-risk karyotypic and molecular abnormalities [i.e. complex karyotype (CK), -17p, -7/7p, p53, RUNX1, ASXL1 mutations] suggests that systematic stratification is feasible to adopt tailored therapy for complete remission [CR] success and OS estimation. In this study, our primary aim was to investigate clinical, cytogenetic and molecular predictors for CR and OS outcome among s-AML patient (pt). Methods: After IRB approval, 178 AML pt diagnosed in Baylor College of Medicine institutions [Michael E. DeBakey VA Houston and Baylor St. Luke's Medical Center] were screened. 68/178 [38%] s-AML pt were selected, however, 55/68(81%) had data available for analysis. Variables with known predictive value for AML prognosis were investigated including age, hemoglobin, white blood cell count [WBC], marrow blast percentage, pre-existing disease [MDS v MPN], karyotypic abnormalities and mutations obtained by next generation sequencing [NGS]. To identify cytogenetic subgroups with differential effect on survival, individual karyotypic abnormalities were “aggregated” into groups exhibiting similar OS [inferior v intermediate v superior survival, see Figure 1, group 0 v 1 v 2]. Kaplan Meier method was used to evaluate differential significant OS among cytogenetic groups. Linear regression model examined independent prognostic effect of “proposed cytogenetic stratification” when adjusting for potential confounders selected from our univariate analysis. Statistical analysis was performed with SAS software, NC, USA and Prism 5. Result: Median age of pt was 67 years (range 42-91). S-AML pt was Male 52/55 (96%), and white 36/55 (65%). Baseline characteristic for the 3 cytogenetic groups are depicted in Table 1. Median OS for all s-AML pt was 90.5 days [d] (range: 3-644). Pre-existing disease was available in 51/55 (93%) pt [10/51 (20%) MPN, 36/51 (70%) MDS, and 5/51(10%) t-AML (p=0.69)]. Intense [7+3