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Updated: Feb 13, 2026

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Prognostic Model Combining Mutational and Cytogenetic Profiles in Acute Myeloid Leukemia Treated with Venetoclax and
Dimitrios Drekolias1,2, Fatima Tuz Zahra1,2, Caroline Fileni3
1Malignant Hematology Department, H. Lee Moffitt Cancer Center, Tampa, Florida.
Abstract:
Venetoclax (VEN) combined with hypomethylating agents (HMA) improves outcomes for patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, yet overall survival (OS) remains variable. We analyzed 506 patients with AML treated with first-line HMA/VEN at Moffitt Cancer Center to develop a genetics-based prognostic model. In multivariate analysis, mutations in TP53, KRAS, JAK2, U2AF1, CBL, and cytogenetic lesions del(7q)/-7, del(17p)/-17/i(17q), del(20q), and MECOM rearrangements predicted inferior OS, whereas IDH1/2 mutations were favorable. A point-based system stratified patients into low-, intermediate-, and high-risk groups with median OS of 54.2, 22.3, and 7.5 months, respectively [P < 0.0001; concordance index (C-index) 0.648]. External validation (n = 126) retained prognostic separation (median OS 24.7, 17.4, and 4.3 months, P = 0.0005; C-index 0.626). Compared with existing HMA/VEN-specific models, our model demonstrated superior low- versus intermediate-risk discrimination (31.9-month separation, P = 0.002; hazard ratio = 0.45, P = 0.003), with a comparable C-index. Our model supports personalized risk stratification for HMA/VEN-treated AML, pending broader validation.
Significance:
This study identifies key mutational and cytogenetic markers associated with treatment response and OS in patients with AML receiving HMA/VEN therapy. By integrating these genetic markers, our new prognostic model offers improved risk stratification, guiding personalized treatment strategies for patients ineligible for intensive chemotherapy. See related commentary by Lachowiez and Loghavi, p. 339.
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