Epidemiology of adult acute myeloid leukemia: Impact of exposures on clinical phenotypes and outcomes after therapy
Introduction
Adult myeloid leukemia (AML) is the most common adult acute leukemia, but its etiology is poorly understood [1]. The mixed-lineage leukemia gene at chromosome 11q23 in topoisomerase II therapy-related AML (tAML) and monosomy 5, del(5q), monosomy 7, and del(7q) in alkylating agent tAML, represent distinct chromosomal abnormalities associated with adverse clinical outcomes [2]. AML in children with Down syndrome is associated GATA1 mutations with excellent outcomes after therapy, but as adults their AML outcomes are similar to average age-matched populations [3]. Important lifestyle and environmental exposures are associated with an increased risk of AML as recognized in prior case-control studies, including obesity, smoking, acetaminophen, and rural/farm habitats, but the impact of these exposures on the clinical phenotype and genotype of AML remains unknown [4], [5], [6], [7], [8], [9]. An important question arises regarding the impact of these potentially etiologic exposures on disease phenotype and clinical outcomes, including overall survival after therapy. This may have particular clinical significance as some factors may be modifiable and may influence clinical decisions. We hypothesize that specific exposures may be independently associated with unique cytogenetic abnormalities at AML diagnosis. Therefore, in this exploratory study, we evaluated relevant exposures in a cohort of adult AML patients with confirmed central cytogenetics analysis and examined associations with cytogenetic categories of AML, complete remission (CR) after treatment, and overall survival (OS).
Section snippets
Patients and methods
295 AML patients diagnosed and treated at Mayo Clinic Florida or Arizona between July 1995 and October 2012 with cytogenetic data available were included in this retrospective study. Patients with acute promyelocytic leukemia (APL) or chronic myeloid leukemia in blast crisis were excluded. The WHO classification of obesity as BMI ≥30 kg/m2 was applied. The hematopoietic cell transplantation-specific comorbidity index (HCTCI) and Eastern Cooperative Oncology Group (ECOG) performance score were
Calculation
In evaluation of our primary aim, we first compared patient characteristics and exposures across the four cytogenetic risk categories of AML using Fisher’s exact test in single variable analysis. Subsequently, we examined associations of patient characteristics and exposures with cytogenetic risk categories of AML using odds ratios (OR) and 95% confidence intervals (CI) from multivariable logistic regression models. To evaluate whether any patient characteristics or exposures predict specific
Results
Patient characteristics are summarized in Table 1. In evaluation of the primary aim, associations of patient characteristics and exposures with cytogenetics are displayed in Table 2 in single variable analysis. Of the 295 patients, 269 (91.2%) had at least one of the potential exposures identified, and 26 (8.8%) did not have any selected exposures. Without adjusting for any potentially confounding variables, sAML, hAML, and prior MDS, all appeared to be significantly associated with poor risk
Discussion
Even though AML is the most common adult leukemia, its etiology is poorly understood. Established risk factors for AML include sAML, inherited predispositions (Fanconi anemia, Downs syndrome, etc.), and toxin exposures [2], [3]. Recent case control studies have suggested environmental and lifestyle exposures as potential etiologic factors for AML including obesity, tobacco use, and some medications [4], [5], [6], [7], [8], [9]. The impact of these exposures on disease phenotypes, clinical
Conclusion
In summary, we have identified potentially modifiable epidemiologic exposures as risk factors for specific cytogenetic risk categories of AML (obesity) and as factors impacting remission after induction chemotherapy (statin therapy and SOT). sAML was associated with poor risk cytogenetics and older patient age. Decreased survival was associated with intermediate abnormal and poor risk cytogenetics in patients age <60 years and HCTCI >3, fair/poor ECOG, tobacco and insulin use in patients age
Author contributions
LF contributed to the conception and design of the project, collection, analysis and interpretation of the data, and drafting and critical revision of the article. LS contributed to the analysis and interpretation of the data and critical revision of the article. MGH contributed to the analysis and interpretation of the data, generation of figures, and critical revision of the article. LJ contributed to the collection of data and critical revision of the article. ND contributed to the analysis
Conflict of interest
None.
Funding
Mayo Clinic Clinical Research Subcommittee provided funding for statistical support.
Acknowledgement
The authors would like acknowledge the contribution of Alison Dowdell in manuscript formatting and editing.
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