Elsevier

Cancer Epidemiology

Volume 39, Issue 6, December 2015, Pages 1084-1092
Cancer Epidemiology

Epidemiology of adult acute myeloid leukemia: Impact of exposures on clinical phenotypes and outcomes after therapy

https://doi.org/10.1016/j.canep.2015.09.003Get rights and content

Highlights

  • We examine associations of epidemiologic exposures and patient outcomes in AML.

  • Obesity is associated with intermediate-abnormal cytogenetic risk category in AML.

  • Statin therapy is associated with complete remission after induction chemotherapy.

  • Complete remission after AML therapy is less likely after solid organ transplant.

Abstract

Background

An increased risk of adult myeloid leukemia (AML) has recently been associated with lifestyle and environmental exposures, including obesity, smoking, some over the counter medications, and rural/farm habitats in case control studies. The association of these exposures with AML cytogenetic categories, outcomes after therapy, and overall survival is unknown.

Methods

Relevant exposures were evaluated in a cohort of 295 consecutive AML patients diagnosed and treated at Mayo Clinic in Florida and Arizona. Standard cytogenetic risk categories were applied and reviewed in a central cytogenetic laboratory. The association of epidemiologic exposures with cytogenetic risk, complete remission after therapy, and overall survival was evaluated using logistic and Cox regression models.

Results

A significant association between obesity and intermediate-abnormal cytogenetics was identified (OR: 1.94, P = 0.025). Similarly, those with secondary AML were more likely to have poor risk (OR: 2.55, P < 0.001) and less likely to have intermediate normal (OR: 0.48, P = 0.003) cytogenetics. In multivariate analysis, overall survival was improved for patients ≥60 years receiving intensive (RR: 0.21, P < 0.001) and non-intensive therapy (RR: 0.40, P < 0.001 compared to no treatment, and was lower for users of tobacco (RR 1.39, P = 0.032), and those with poor risk cytogenetics (RR: 3.96, P = 0.002) or poor performance status (RR: 1.69, P < 0.001). Furthermore, an association between statin use at the time of diagnosis (OR: 2.89, P = 0.016) and increased complete remission after intensive chemotherapy was identified, while prior solid organ transplantation was associated with significantly lower complete remission rate after therapy (OR: 0.10, P = 0.035).

Conclusion

Our results provide evidence that specific epidemiologic exposures, including obesity, are significantly associated with unique AML cytogenetic risk categories and response to therapy. This supports a link between patient lifestyles, clinical exposures, and leukemogenesis.

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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