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Increased BMI and acute promyelocytic leukemia
Submit responseTo the Editor,
We read with interest the recent article by M. Breccia et al describing the correlation of an increased body mass index (BMI) with a higher risk of disease relapse and differentiation syndrome in 144 newly diagnosed genetically confirmed acute promyelocytic leukemia (APL) patients treated at a single institution.1 As the authors describe, previous reports and their current work, consistently identify increased body mass index (BMI) to be strongly associated with the diagnosis of APL.2 The pathogenesis of de novo APL (dn-APL) is unknown but obesity and increased BMI appear to be risk factors.
Therapy-related acute promyelocytic leukemia (t-APL) is a well- recognized form of APL for which the underlying etiology has been well characterized.3 Although the pathogenic pathway has been best characterized following exposure to drugs targeting topoisomerase II, it has also been reported with exposure to alkylating agents and radiation.4 In contrast, the majority of APL cases arise de novo without an identifiable cause. Although t-APL is increasingly recognized, most clinical trials of APL restrict eligibility to those patients with de novo disease or provide no information allowing for distinction of t-APL independent of the entire study population.5-7 If increasing BMI or obesity is in some way linked to APL pathogenesis, we hypothesized the t- APL, an entity arising in the setting of chemotherapy or radiation-induced DNA damage, would not share these features. In a retrospective analysis of 64 APL patients treated with contemporary all-trans-retinoic acid (ATRA) and anthracycline-based therapy at our institution, we analyzed demographics and clinical features to assess for differences in these two etiologically distinct patient groups.8 Compared to patients with t-APL (n=11), those with dn-APL (n=53) had a greater median BMI (31.33 versus 28.48), incidence of obesity (60.4% versus 27.3%) (p =0.04) and history of hyperlipidemia (45.3% versus 18.2%) (p=0.01).
Although our observations could provide further support for the hypothesis that abnormalities in lipid homeostasis may in some way be of pathogenic relevance in dn-APL, our analysis was compromised by sample size. We would be very interested to learn if the authors made this distinction between de novo and t-APL in their analysis and if yes, could they share this information?
Respectfully submitted,
Michelle A. Elliott,
Louis Letendre,
Mark R. Litzow
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905 Corresponding Author Michelle Elliott MD Associate Professor of Medicine Division of Hematology/ Department of Internal Medicine Mayo Clinic, 200 First St. SW. Rochester, MN 55905 Email: Elliott.michelle@mayo.edu
Conflict of Interest: Authors declare no conflict of interest
References
1.Breccia M, Mazzarella L, Bagnardi, V et al. Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols Blood. 2012;119(1):49-54. 2.Estey E, Thall P, Kantarjian H, Pierce S, Kornblau S, Keating M. Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia. Leukemia 1997;11(10):1661-1664. 3.Mistry AR, Felix CA, Whitmarsh RJ, et al. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. New Engl J Med 2005;352(15):1529-1538. 4.Beaumont M, Sanz M, Carli PM, et al. Therapy-related acute promyelocytic leukemia. J Clin Oncol 2003;21(11):2123-2137. 5.Sanz MA, Montesinos P, Rayon C, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010;115(25):5137-5146. 6.Lo-Coco F, Avvisati G, Vignetti M, et al. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010;116(17):3171-3179. 7.Powell BL, Moser B, Stock W, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010;116(19):3751-3757. 8.Elliott MA, Letendre, L, Tefferi, A, et al. Therapy-related acute promyelocytic leukemia: observations relating to APL pathogenesis and therapy. Eur J Haem 2012. doi: 10.1111/j.1600-0609.2011.01727.x
Conflict of Interest:
None declared
