The Epidemiology and Clinical Associations of Stroke in Patients with Acute Myeloid Leukemia: A Review of 10,972 Admissions from the 2012 National Inpatient Sample

Background: Patients withacute myeloid leukemia (AML) are at increased risk for both hemorrhage and thrombosis, including in the central nervous system. There is limited data on the incidence, clinical association and mortality associated with cerebrovascular accident (CVA) in hospitalized patients with active AML. The aim of this study is to evaluate the epidemiology and mortality of hospitalized patients with AML who suffered concurrent stroke from a large national database.

Methods: Using the 2012 National Inpatient Sample (NIS), admissions with an International Classification of Diseases, 9^th Revision, Clinical Modification (ICD-9-CM) codes for AML without remission and AML in relapse (205.00 and 205.02, respectively) were extracted, and correlated with age, gender, length of stay and mortality. All CVA (ICD-9-CM 434.91) data were extracted as well for comparison of mortality, length of stay (LOS).

Results: Of the 7,296,968 unweighted admissions in the 2012 NIS, 9384 involved AML patients who had not yet achieved remission, and 1600 involved relapsed AML (Prevalence of 0.12% and 0.021% respectively). Of the combined group of admitted patients with active AML (N=10,984), 65 patients (0.59%) had a concomitant CVA (either hemorrhagic or ischemic, of whom 56 (0.51%) had active disease and 9 (0.08%) had relapsed disease). Compared to all other active AML patients, those who developed stroke were older (Mean age 66 y/o vs 58 y/o P=0.003), had longer LOS (20 days vs 12 days P= 0.53), were predominantly female (55% vs 45%; p=0.078) and had significantly higher inpatient mortality rates (36.9% vs 10.5%; OR 3.5; 95%CI 2.2, 5.5; P<0.0001). AML patients with CVA had significantly higher inpatient mortality then all admitted patients with stroke (36.9% vs 6.7%; OR 5.5; 95%CI 3.5, 8.8; P<0.0001). Multivariate logistic regression attempting to find significant clinical associations in AML patients who develop stroke, after controlling for confounding variables, found that acute renal failure with tubular necrosis(OR 4.47; 95%CI 1.8, 11.2; P=0.0013), hypernatremia (OR 3.85; 95%CI 1.6, 9.1; P=0.002), urinary tract infection (OR 3.28; CI95% 1.8, 6.1; P=0.0002) and secondary thrombocytopenia (OR 2.92; 95%CI 1.5, 5.7; P=0.0018) were all significantly predictive, as were mechanical ventilation >96 hours (OR 4.92; CI95% 1.02, 23.6; P=0.047) and continuous positive airway pressure ventilation (OR 3.03; CI95% 1.11, 8.26; P=0.031). Disseminated intravascular coagulation (DIC) and leukocytosis were more prevalent in AML patients with CVA compare to all AML patients, but the difference did not reach statistical significance.

Conclusions: CVA in patients with active AML was strongly associated with older age and higher mortality, and appeared to be a relatively rare event, occurring in only 0.59% of patients. There was no statistically significant difference in LOS or gender distribution between those who developed CVA and those who did not amont active AML patients. As compared to all CVA patients, active AML patients with CVA had 5-fold higher risk of mortality. Significant acute renal failure, hypernatremia and thrombocytopenia appear to portend a higher risk of stroke in patients with active AML. It is unclear if UTI, and the need for mechanical ventilation is a predictor of stroke, as much as they may be a ramification of it. While more common in AML patients with CVA vs AML patients without CVA, we did not find DIC or hyperleukocytosis to be significantly predictive.