Impact of Cytogenetic Response to Therapy on Long-Term Survival in Acute Myeloid Leukemia

Prognostication in acute myeloid leukemia (AML) relies on clinical, molecular, and cytogenetic factors. In this retrospective study, we examined the impact of different levels of cytogenetic response on overall survival (OS) and event-free survival (EFS) in AML. Among 973 adult AML patients treated at Cleveland Clinic (5/2017-9/2023), 563 patients had baseline cytogenetic data and post-treatment response assessment available. Based on baseline and response cytogenetic status, patients were categorized into: normal to normal (NL-Cy to NL-Cy, n = 221, 39%), normal or abnormal to gain (NL/Abnl-Cy to Gain-Cy, n = 46, 8.2%), abnormal to persistent (Abnl-Cy to Persistent-Cy, n = 81, 14%), abnormal to partial response (Abnl-Cy to Partial-Cy, n = 20, 3.6%), and abnormal to complete response (Abnl-Cy to NL-Cy, n = 195, 35%). Landmark analysis was used to account for post-treatment assessments. The cohort had a median age of 62 years (interquartile range: 52-69), 256 females (45%), 90% were White, and median follow-up of 45.8 months (range: 0.73-191.3). The median OS and hazard ratios (HRs) from multivariable regression analysis were as follows: NL-Cy to NL-Cy: 37 months (95% CI: 27-91), HR = reference; NL/Abnl-Cy to Gain-Cy: 14 months (95% CI: 8.6-30), HR = 1.5 (95% CI: 0.99-2.39); Abnl-Cy to Persistent-Cy: 13 months (95% CI: 12-18), HR = 1.61 (95% CI: 1.13-2.31); Abnl-Cy to Partial-Cy: 25 months (95% CI: 14-NC), HR = 0.76 (95% CI: 0.39-1.49); and Abnl-Cy to NL-Cy: 27 months (95% CI: 19-101), HR = 1.25 (95% CI: 0.93-1.68) (p = 0.038). Achieving cytogenetic remission, complete or partial, was associated with better survival outcomes. These findings highlight the importance of monitoring cytogenetic responses to inform treatment decisions and support integrating cytogenetic response into risk-adapted, personalized AML management strategies.