Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) represent a group of hematological disorders that are characterized by inefficient hematopoiesis, resulting in cytopenias and dysplasias in the blood. MDS often manifests in older patients, with a median age at diagnosis of 70 to 75 years. This older population is frequently diagnosed with comorbidities such as cardiovascular, pulmonary, and malignant diseases.¹

Common Comorbidities in Patients With MDS

Della Porta et al. studied the prevalence of comorbidities in patients with MDS, as well as the relationship of these comorbidities with demographic and disease-related factors. Additionally, the authors developed the MDS-specific comorbidity index (MDS-CI). This tool, together with the World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS), can lead to an improved prognostic stratification of patients with MDS and therefore offer tailored treatment strategies.² Other comorbidity indexes have also been developed, such as the hematopoietic cell transplantation (HCT)-specific comorbidity index (HCT-CI), which is used to determine whether a patient is eligible for a stem cell transplantation.³ 

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A high prevalence of comorbidities has been reported in patients with MDS. In the Della Porta et al. study, 54% of the patients presented with at least 1 comorbidity at the time of diagnosis. The authors also observed that comorbidities were associated with the age of the patients, with a prevalence of 29% in patients under 50 years of age vs 71% in patients over the age of 75 years.²

The comorbidity most frequently reported in this study was cardiac disease, which was identified in 25% of patients. This included arrhythmia, heart valve disease, coronary artery disease, myocardial infarction, congestive heart failure, and ejection fraction <50%. Cardiac disease was also the main cause of nonleukemic death. Other identified comorbidities included ²:

• Cerebrovascular transient ischemic attack and/or ischemic or hemorrhagic cerebrovascular accident
• Pulmonary disease (including dyspnea at rest or during activity and a need of oxygen)
• Hepatic disease (including chronic hepatitis, fibrosis, and persistent bilirubin increase)
• Renal disease (including a requirement for renal dialysis or renal transplant)
• Solid malignancies
• Rheumatological disease (including systemic lupus erythematosus and rheumatoid arthritis)
• Gastrointestinal disease (including Crohn’s disease)
• Diabetes
• Endocrine disease (including thyroid and adrenal disorders)
• Obesity
• Psychiatric diseases (including depression)

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Prognostic Impact of Comorbidities in Patients With MDS

Comorbidities are important factors to consider in the prognostic evaluation of patients with MDS. These diseases often compromise organ function, affecting quality of life and requiring therapeutic intervention. They can also influence the therapeutic course of each patient, preventing patients from undergoing treatments such as allogeneic stem cell transplantation.³ 

In low-risk patients, comorbidities affect the natural course of disease by increasing the risk of death. In these patients, assessing comorbidities is important for establishing supportive care and follow-up. In high-risk patients, comorbidities influence clinical outcomes as they often limit the eligibility of patients to undergo treatments as well as their tolerance to those treatments.²

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The Della Porta et al. report revealed that comorbidities had a significant impact on clinical outcomes, as they impacted both nonleukemic death and overall survival. From the list of comorbidities identified in the study, cardiac, liver, renal, pulmonary diseases, and solid tumors independently affected the risk of nonleukemic death.²

A different study from Rozema et al. also found a high prevalence of comorbidities in patients with MDS. They discovered a significant portion of the studied population with prior malignancy and shorter overall survival. The overall survival was not linked to radiotherapy or chemotherapy treatments.¹

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References

1. Rozema J, Hoogendoorn M, Kibbelaar R, van den Berg E, Veeger N, van Roon E. Comorbidities and malignancies negatively affect survival in myelodysplastic syndromes: a population-based study. Blood Adv. 2021;5(5):1344-1351. doi:10.1182/bloodadvances.2020003381
2. Della Porta MG, Malcovati L, Strupp C, et al. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica. 2011;96(3):441-449. doi:10.3324/haematol.2010.033506
3. Kasprzak A, Nachtkamp K, Gattermann N, Germing U. Assessing the prognosis of patients with myelodysplastic syndromes (MDS). Cancers (Basel). 2022;14(8):1941. doi:10.3390/cancers14081941

Reviewed by Harshi Dhingra, MD, on 6/17/2023.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.