What is Myelodysplastic syndrome (MDS)?

From the Guidelines

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, leading to blood cytopenias and a high risk of transformation to acute myeloid leukemia (AML). The diagnosis of MDS is based on blood and marrow examination, showing blood cytopenias, hypercellular marrow with dysplasia, with or without an excess of immature marrow cells (blasts) 1. The pathophysiology of MDS involves a multistep process with cytogenetic changes and/or gene mutations, and widespread gene hypermethylation at advanced stages 1.

Key Characteristics of MDS

• Ineffective hematopoiesis leading to blood cytopenias
• High risk of transformation to AML
• Clonal hematopoietic stem cell disorder
• Characterized by dysplastic changes in bone marrow cells

Diagnosis and Classification

The diagnosis of MDS requires a comprehensive approach, including morphologic studies of peripheral blood and bone marrow, cytogenetics, and molecular markers 1. The World Health Organization (WHO) classification of MDS identifies several entities, including MDS with single lineage dysplasia, MDS with ring sideroblasts, and MDS with excess blasts 1. The Revised International Prognostic Scoring System (IPSS-R) is used to predict the outcome of patients with MDS, based on the number and severity of cytopenias, percentage of bone marrow blasts, and cytogenetic abnormalities 1.

Treatment Options

Treatment of MDS depends on disease risk stratification, patient age, and comorbidities. For lower-risk MDS, options include supportive care with red blood cell and platelet transfusions, erythropoiesis-stimulating agents, and lenalidomide [@Example@]. For higher-risk MDS, hypomethylating agents such as azacitidine or decitabine are standard treatments, and allogeneic hematopoietic stem cell transplantation remains the only potentially curative option for eligible patients [@Example@].

Recent Updates and Recommendations

Recent updates to the WHO classification and the IPSS-R have improved the diagnostic and prognostic capabilities of MDS 1. The use of next-generation sequencing has also become a powerful tool in the diagnosis and treatment of MDS, allowing for the identification of specific genetic mutations and the development of targeted therapies 1. Regular monitoring of blood counts and iron chelation therapy with deferasirox should be considered for transfusion-dependent patients [@Example@].

From the FDA Drug Label

14 CLINICAL STUDIES 14.1 Myelodysplastic Syndromes (MDS)

Study 1 was a randomized, open-label, controlled trial carried out in 53 U. S sites compared the safety and efficacy of subcutaneous azacitidine for injection plus supportive care with supportive care alone (“observation”) in adult patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS): refractory anemia (RA), RA with ringed sideroblasts (RARS), RA with excess blasts (RAEB), RAEB in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL)

Myelodysplastic syndrome (MDS) is a group of disorders characterized by the following subtypes:

• Refractory anemia (RA)
• RA with ringed sideroblasts (RARS)
• RA with excess blasts (RAEB)
• RAEB in transformation (RAEB-T)
• Chronic myelomonocytic leukemia (CMMoL) 2

From the Research

Definition and Characteristics of Myelodysplastic Syndrome (MDS)

• Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML) 3, 4, 5, 6, 7.
• MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy 3, 7.
• Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy 3.

Risk Stratification and Prognosis

• Prognosis of patients with MDS can be calculated using a number of scoring systems, including the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) 3, 6.
• The IPSS includes analysis of peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics 3.
• Patients with lower-risk MDS have a median survival of approximately 3 to 10 years, whereas patients with higher-risk disease have a median survival of less than 3 years 7.

Treatment Options

• Therapy for MDS is selected based on risk, transfusion needs, percent of bone marrow blasts, and cytogenetic and mutational profiles 3, 5, 7.
• Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation 3, 4, 5, 6, 7.
• Allogeneic stem cell transplantation is the only potential cure for MDS and is considered for higher-risk patients 5, 6, 7.
• Treatment goals for lower-risk MDS are to improve cytopenia, quality of life, and overall survival, while treatment goals for higher-risk MDS are to prolong survival 5, 7.