The Prognostic Utility of Normal Karyotype Fraction in Acute Myeloid Leukemia
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The prognostic significance of the proportion of normal metaphases detected at diagnosis in acute myeloid leukemia (AML) has not been systematically evaluated. PATIENTS AND METHODS: We conducted a retrospective cohort study of 893 adult AML patients treated at Cleveland Clinic between January 2015 and September 2023 who underwent conventional cytogenetic analysis. Normal karyotype fraction (NKF) was defined as the proportion of normal metaphases among all metaphases analyzed at diagnosis. NKF was evaluated as a continuous measure and categorized using three-group (NKF = 0, 0 < NKF < 1, NKF = 1) and 5-group functional classification systems. Primary outcomes included overall survival (OS), event-free survival (EFS), composite complete remission (CR/CRi), and relapse. Multivariable Cox proportional hazards and logistic regression models were adjusted for established prognostic covariates. RESULTS: NKF demonstrated a bimodal distribution across the cohort. Patients with NKF = 1 achieved the highest CR/CRi rate (64%) and longest median OS (16 months) and EFS (11 months). In multivariable analyses, NKF = 1 was independently associated with improved OS (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.61-0.97) and EFS (HR, 0.73, 95% CI, 0.58-0.91), and higher odds of achieving CR/CRi (odds ratio 1.72, 95% CI, 1.10-2.70) compared with NKF = 0. EFS was significantly associated with NKF categories in both classification systems (P < .05). CONCLUSION: NKF is a readily obtainable cytogenetic parameter that was associated with treatment response and survival in this cohort. External validation and prospective studies are warranted to support its use in clinical risk stratification frameworks.
Authors: Ameed Bawwab, Emily C. Zabor, Lana Khatib, Moath Albliwi, John Hanna, Jessica El-Asmar, Daniel P. Nurse, Hasan Abuamsha, Yomna Abu-Farsakh, Asad Rauf, Ahmed Mohamed, Muaz Alsabbagh Alchirazi, Joy Nakitandwe, David S. Bosler, Prerana Bangalore Parthasarathy, Tyler Alban, Akriti G. Jain, John C. Molina, Sophia Balderman, Abhay Singh, Aaron T. Gerds, Sudipto Mukherjee, Ronald Sobecks, Anjali S. Advani, Hetty E. Carraway, Caroline Astbury, Moaath K. Mustafa Ali
Institution: Cleveland Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,890
OpenAlex ID: W7165420974