Association between glycemic control, age, and outcomes among intensively treated patients with acute myeloid leukemia
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To investigate the impact of hyperglycemia and glycemic variability during intensive acute myeloid leukemia therapy (AML) on outcomes by age.
Retrospective study of 262 consecutive patients with newly diagnosed AML hospitalized for intensive induction. Hyperglycemia was assessed by mean blood glucose (BG) (mg/dL) during hospitalization and glycemic variability was determined by the standard deviation (SD) of mean BG. Outcomes were complete remission ± incomplete count recovery (CR + CRi), and overall survival (OS). We used logistic regression to evaluate CR + CRi, and Cox proportional hazard models for OS, stratified by age (< 60 vs ≥ 60 years).
Older patients (N = 138, median age 70) had higher baseline comorbidity (CCI > 1 60.1% vs 25.8%) and prevalence of diabetes (20.3% vs 7.3%) compared to younger (N = 124, median age 47). The mean ± SD number of BG values obtained per patient during hospitalization was 61 ± 71. The mean (± SD) glucose (mg/dL) during hospitalization was 121.7 (25.9) in older patients (≥ 60 years) versus 111.6 (16.4) in younger. In older patients, higher mean glucose and greater glycemic variability were associated with lower odds of remission (OR 0.80, 95% CI 0.69–0.93 and OR 0.73, 95% CI 0.61–0.88 respectively, per 10-unit increase) and higher mortality rates (HR 1.13, 95% CI 1.05–1.21 and HR 1.17, 95% CI 1.09–1.26, respectively, per 10-unit increase) in multivariate analyses.
Our observations that hyperglycemia and increased glycemic variability were associated with lower remission rates and increased mortality in older patients suggest glycemic control may be a potentially modifiable factor to improve AML outcomes.
KeywordsAcute myeloid leukemia Hyperglycemia Glycemic variability Diabetes Older
We thank Karen Klein, MA ELS (Research Support Core Wake Forest School of Medicine Clinical Translational Science Institute), for her editorial contributions to the manuscript.
Research reported in this publication was supported by the National Cancer Institute’s Cancer Center Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Heidi. D. Klepin was supported by a Paul Beeson Career Development Award in Aging Research (K23AG038361; supported by NIA, AFAR, The John A. Hartford Foundation, and The Atlantic Philanthropies) and The Gabrielle’s Angel Foundation for Cancer Research.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Adult acute myeloid leukemia (PDR)- Health Professional Version (2016). NIH: National Cancer InstituteGoogle Scholar
- 2.Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3):453–474. https://doi.org/10.1182/blood-2009-07-235358 CrossRefPubMedGoogle Scholar
- 5.Etienne A, Esterni B, Charbonnier A, Mozziconacci MJ, Arnoulet C, Coso D, Puig B, Gastaut JA, Maraninchi D, Vey N (2007) Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer 109(7):1376–1383CrossRefGoogle Scholar
- 6.Deschler B, Ihorst G, Platzbecker U, Germing U, Marz E, de Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lubbert M (2013) Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica 98(2):208–216. https://doi.org/10.3324/haematol.2012.067892 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Giles FJ, Borthakur G, Ravandi F, Faderl S, Verstovsek S, Thomas D, Wierda W, Ferrajoli A, Kornblau S, Pierce S, Albitar M, Cortes J, Kantarjian H (2007) The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol 136(4):624–627CrossRefGoogle Scholar
- 9.Savic A, Kvrgic V, Rajic N, Urosevic I, Kovacevic D, Percic I, Popovic S (2012) The hematopoietic cell transplantation comorbidity index is a predictor of early death and survival in adult acute myeloid leukemia patients. Leukemia Res 36(4):479–482. https://doi.org/10.1016/j.leukres.2011.11.021 CrossRefGoogle Scholar
- 10.Ali NA, O'Brien JM Jr, Blum W, Byrd JC, Klisovic RB, Marcucci G, Phillips G, Marsh CB, Lemeshow S, Grever MR (2007) Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality. Cancer 110(1):96–102. https://doi.org/10.1002/cncr.22777 CrossRefPubMedGoogle Scholar
- 11.Matias Cdo N, Lima V, Teixeira HM, Souto FR, Magalhaes V (2013) Hyperglycemia increases the complicated infection and mortality rates during induction therapy in adult acute leukemia patients. Revista Brasileira de Hematologia e Hemoterapia 35(1):39–43. https://doi.org/10.5581/1516-8484.20130013 CrossRefPubMedGoogle Scholar
- 18.Mendez CE, Mok KT, Ata A, Tanenberg RJ, Calles-Escandon J, Umpierrez GE (2013) Increased glycemic variability is independently associated with length of stay and mortality in noncritically ill hospitalized patients. Diabet Care 36(12):4091–4097. https://doi.org/10.2337/dc12-2430 CrossRefGoogle Scholar
- 20.Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a southwest oncology group/eastern cooperative oncology group study. Blood 96(13):4075–4083PubMedGoogle Scholar
- 21.Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21(24):4642–4649. https://doi.org/10.1200/jco.2003.04.036 CrossRefPubMedGoogle Scholar
- 24.Zeng L, Biernacka KM, Holly JM, Jarrett C, Morrison AA, Morgan A, Winters ZE, Foulstone EJ, Shield JP, Perks CM (2010) Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocrine-Related Cancer 17(2):539–551. https://doi.org/10.1677/erc-09-0221 CrossRefPubMedGoogle Scholar
- 26.Muggeo M, Verlato G, Bonora E, Zoppini G, Corbellini M, de Marco R (1997) Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona diabetes study. Circulation 96(6):1750–1754CrossRefGoogle Scholar
- 28.Meugnier E, Faraj M, Rome S, Beauregard G, Michaut A, Pelloux V, Chiasson JL, Laville M, Clement K, Vidal H, Rabasa-Lhoret R (2007) Acute hyperglycemia induces a global downregulation of gene expression in adipose tissue and skeletal muscle of healthy subjects. Diabetes 56(4):992–999. https://doi.org/10.2337/db06-1242 CrossRefPubMedGoogle Scholar
- 31.Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Zuodar G, Ceriello A (2005) Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production. Atherosclerosis 183(2):259–267. https://doi.org/10.1016/j.atherosclerosis.2005.03.015 CrossRefPubMedGoogle Scholar
- 32.Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabo C, Ceriello A (2004) Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly (ADP-ribose) polymerase. J Thromb Haemos 2(8):1453–1459. https://doi.org/10.1111/j.1538-7836.2004.00835.x CrossRefGoogle Scholar