Outcomes of Patients with Myelodysplastic Syndrome and Cardiovascular Disease

Background

Myelodysplastic syndrome (MDS) encompasses a group of hematopoietic stem cell malignancies characterized by morphologic dysplasia, bone marrow failure with associated cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The annual incidence of MDS is approximately 5 per 100,000 people in the United States, with a median age at diagnosis of 70 years. Various risk stratification tools can be used to estimate survival and outcomes in these patients. While patients with low-risk disease can have prolonged survival, high-risk patients have much shorter survival of less than 3 years. Treatment for low-risk disease is directed at improving cytopenias, while the standard of care for patients with high-risk disease is DNA methyltransferase inhibitor (DNMTi) therapy with agents such as azacitidine, decitabine or decitabine-cedazuridine. Hematopoietic stem cell transplantation (HSCT) is the only potential curative therapy indicated for fit patients with high-risk disease. Previous European studies described poor outcomes in patients with hematopoietic malignancies and cardiovascular diseases (CVD), as well as the association of cardiac biomarkers in predicting outcomes in patients with MDS.

Objectives and Methods

This study aimed to evaluate the impact of CVD on outcomes of patients diagnosed with MDS who were treated at the University of Maryland Medical Center. We retrospectively reviewed the charts of 98 patients who were diagnosed with MDS or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) from 2004 to 2019. We collected baseline patient demographic information including, but not limited to, age at diagnosis, race, gender, date of initial diagnosis, date of treatment initiation, previous laboratory and bone marrow biopsy results, cytogenetic results, myeloid mutation results, treatments received, number of cycles of treatment, response to treatment, and date of last follow up or date of death. In addition, we also collected data on pre-existing CVD, as well as the development of CVD after diagnosis and interventions needed.

This data was used to determine patient survival outcomes, overall survival (OS), progression-free survival (PFS), time to response (TTR), disease free survival (DFS), duration of response (DOR), time to decline in left ventricular ejection fraction (LVEF) to less than 40%, and the outcomes of patients with and without CVD. OS is defined as time from the start of treatment to date of death from any cause. PFS is time from the start of treatment to progression or to death without progression. DFS is defined as time from the start of treatment to date of disease recurrence or to death from any cause. DOR is measured from the time at which measurement criteria are first met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.

Results

Patient demographic and clinical characteristics are shown in table 1 and 2. Forty three patients (44%) were alive at last follow up, with median follow up time of 3.96 years. The median OS was 1.67 years (95% CI of 1.29 to 2.81 years). Median OS was higher in patients without CVD (2 years) as compared to those with CVD (1 year), p-value 0.003 (Figure 1). Median OS was similar in non-smokers as compared to smokers, p-value 0.33 (Figure 2). Median DOR was 0.86 years (95% CI of 0.64 to 2.26 years). Two out of 98 patients had a cardiac stress test done, three had fatal cardiac event. Twenty five cases (26%) had a major adverse cardiovascular event.

Discussion

This single institution study shows that the presence of CVD is associated with adverse outcomes in patients with MDS. While this is a retrospective review, there is a statistically significant difference in the median OS of patients with CVD as compared to those without CVD. This underscores the importance of recognizing comorbid cardiovascular conditions in patients who are diagnosed with MDS as they can portend a poor outcome as well as the need for comprehensive cardiovascular management in this population. Further prospective studies should explore interventions targeting cardiovascular health in MDS patients. Additional research into specific types of CVD and their differential impacts on MDS outcomes could provide deeper insights into managing these comorbidities.

No relevant conflicts of interest to declare.