A High Prevalence of Obesity in Acute Promyelocytic Leukemia (APL): Is Obesity a Risk Factor for APL? Implication of Targeted Therapy to Control Obesity and APL Prevention.

Epidemiological and occupational risk factors reveal that acute promyelocytic leukemia (APL) predominantly in adults and has an increased incidence in certain regions such as Latin America and northeastern Italy. Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. RARs are implicated in the development of APL and metabolic diseases such as obesity and diabetes mellitus; however, there is no consistent link reported between APL and obesity. Risk factors associated with the development of APL are unclear at this time. In our experience, we observed that several patients diagnosed with APL are morbidly obese and pose a challenge in chemotherapy dosing.

In an institutional review board approved study, we conducted a case-controlled study on patients diagnosed with acute myeloid leukemia (AML) at our institute between January 1999 and December 2008.

In this single institution study, 469 patients diagnosed with AML during this time period, 61 (13%) patients had APL. Of those, 44 patients had complete data sets available for final analysis. Forty nine patients who served as control subjects with non-APL acute myeloid leukemia matched for age and sex were obtained from the same patient set. The median age at diagnoses of APL was 41 years vs. 50 years for the non-APL group. Among the APL group, 23 (52%) patients were female. Thirty patients (69%) were Caucasians, 9 (19%) African Americans and 5 (11%) Hispanics. All patients with APL had cytogenetic confirmation of t(15; 17). Additional cytogenetic abnormalities were present in 11 (25%) APL patients. Other cytogenetics abnormalities were trisomy 8 (14%), 21 (3%), del 20q (3%) del 12q (3%) and complex karyotype (2%). All patients received induction therapy with all-trans-retinoic acid (ATRA) and an anthracycline (daunorubicin or idarubicin) at the time of induction. Thirty six (81%) patients with APL underwent dose adjustment based on the patient's ideal body weight, while 30 (63%) patients with non-APL acute myeloid leukemia received dose reduction based on ideal body weight. Median overall survival was 38.3 month (22.8 to 55.6) and 20.2 months (18.6 to 31.6) among APL and non-APL patients (logrank p=0.002) Using the Wilcoxon rank sum test, the median weight of patients with APL was 96.2 kg (range, 59.8-203.5), and the median weight of patients with non-APL was 81.4 kg (range, 49.6-151.5) (p=0.003). The median body mass index (BMI) for APL patients was 32.4 compared to 27.3 among non-APL patients (p=0.008). 57% of APL patients were obese (BMI>30) compared to only 31% non-APL patients (chi-square p=0.01). Controlling for disease subtype, neither BMI (p=0.111) nor obesity status (p=0.203) had statistically significant impact on APL survival. Hypertension and dyslipidemia were the frequent co-morbid illnesses at the time of diagnosis of APL.

These results support that a higher proportion of patients diagnosed with APL have a BMI of >30 in comparison to patients with non-APL AML. Larger population-based studies will help define if obesity is a risk factor for developing APL. If this link is confirmed, RXR ligands need to be explored for specific therapeutic applications among obese individuals.

No relevant conflicts of interest to declare.