MDS-426: Cardiovascular Disease and Marrow Vascular Markers in Patients with Myeloid Malignancies

Abstract

Context: The incidence of both myeloid malignancies and cardiovascular disease (CVD) increases with age. We aimed to study whether the presence of CVD is associated with worse outcomes in patients with myeloid malignancies and to delineate a possible mechanism. Objective: Compare overall survival (OS) and marrow vascular density among patients with and without CVD. Design: We retrospectively reviewed 295 previously untreated patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MDS/MPN). CVD included congestive heart failure, coronary artery disease, arrhythmia, peripheral vascular disease, congenital heart disease, and/or cerebrovascular accident. CVD and no-CVD patient characteristics were compared using Fisher’s exact and t-tests. OS was estimated by Kaplan-Meier analysis. Microvascular density (MVD) was determined in CD34-stained bone marrow sections of 20 MDS patients (11 with and 9 without CVD). The mean number of blood vessels was calculated for each sample and compared using the t-test. Setting: University of Maryland Greenebaum Comprehensive Cancer Center, in Baltimore, Maryland. Patients: The study included 228 (77%) patients with AML and 67 (23%) with MDS or MDS/MPN, of whom 92 had CVD (31%) and 203 (69%) did not. Median age at diagnosis was 66 years (range 19–89). Results: For AML patients, 1-, 2- and 3-year OS in CVD vs no-CVD groups was 46% vs 70%, 34% vs 53%, and 26% vs 43%, respectively [HR 1.9, 95% CI = 1.35, 2.67]. For MDS patients, 44% vs 81%, 26% vs 51%, and 26% vs 49% [HR 2.52, 95% CI = 1.27, 5]. In a multivariable regression model accounting for age, performance status, and karyotype, CVD independently predicted worse OS. We hypothesized that treatment response might be affected by MVD, but we did not find a significant difference in MVD in patients with CVD vs no-CVD (mean score 17 vs 22, p=0.4), ever smoker vs never smoker (mean score 19 vs 20, p=0.9), or with vs without diabetes mellitus (mean score 23 vs 13, p=0.1), although the lack of significant difference may be attributed to the small sample size. Conclusions: CVD is a predictor of survival outcomes in patients with AML and MDS. Variability in MVD is a possible mechanism of impaired treatment response in CVD patients, which warrants further evaluation.