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Haematologica. 2019 May 9. pii: haematol.2018.208637. doi: 10.3324/haematol.2018.208637. [Epub ahead of print]

Comparisons of commonly used frontline regimens on survival outcomes in patients age 70 years and older with acute myeloid leukemia.

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Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
Maury Regional Cancer Center, Columbia, TN.
Senior Adult Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL.
Malignant Hematology Department, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
H. Lee Moffitt Cancer Center & Research Institute.


In older patients with acute myeloid leukemia, the more frequent presence of biologically inherent therapy-resistant disease and increased comorbidities translate to poor overall survival and therapeutic challenges. Optimal frontline therapies for older patients with acute myeloid leukemia remain controversial. We retrospectively evaluated survival outcomes in 980 elderly (≥70 years) acute myeloid leukemia patients from a single institution between 1995 and 2016. Four treatment categories were compared: high-intensity (daunorubicin/cytarabine or equivalent), hypomethylating agent, low-intensity (low-dose cytarabine or similar without hypomethylating agents), and supportive care therapy (including hydroxyurea). At a median follow-up of 20.5 months, the median overall survival for the entire cohort was 7.1 months. Multivariate analysis identified secondary acute myeloid leukemia, poor-risk cytogenetics, performance status, frontline therapy, age, white blood cell count, platelet count, and hemoglobin level at diagnosis as having an impact on survival. High-intensity therapy was used in 360 patients (36.7%), hypomethylating agent in 255 (26.0%), low-intensity therapy in 91 (9.3%), and supportive care in 274 (28.0%). Pairwise comparisons between hypomethylating agent therapy and the 3 other treatment groups demonstrated statistically significant superior median overall survival with hypomethylating agent (14.4 months) versus high-intensity therapy (10.8 months, hazard ratio 1.35, 95% confidence interval 1.10-1.65, P = .004), low-intensity therapy (5.9 months, hazard ratio 2.01, 95% confidence interval 1.53-2.62, P < .0001), and supportive care (2.1 months, hazard ratio 2.94, 95% confidence interval 2.39-3.61, P < .0001). Our results indicate a significant survival benefit with hypomethylating agents compared to high-intensity, low-intensity, or supportive care. Additionally, high-intensity chemotherapy resulted in superior overall outcomes compared to low-intensity therapy and supportive care. Results from this study highlight the need for novel therapeutic approaches besides utilization of intensive chemotherapy in this specific aged population.


Acute Myeloid Leukemia; Cytogenetics and Molecular Genetics; aged AML patients; frontline therapies; hypomethylating agent

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