What is myelodysplasia?

Myelodysplastic Syndromes (MDS): Definition and Characteristics

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by peripheral blood cytopenia with typically hypercellular bone marrow and dysplasia of cellular elements, which can progress to acute myeloid leukemia in one-third of cases. 1

Key Features of MDS

• MDS are clonal hematopoietic stem cell disorders that predominate in the elderly, with a median age at diagnosis of approximately 70 years 1, 2
• The incidence is about 4 cases/100,000 inhabitants/year, increasing to 40-50/100,000 in patients aged ≥70 years 1
• MDS is more common in men than women (yearly incidence rates of approximately 5.4 vs 2.9 per 100,000) 2

Etiology

• The etiology is unknown in more than 80% of patients (idiopathic) 1
• Known causes (approximately 15% of cases) include: 1
  • Previous exposure to chemotherapy (especially alkylating agents and purine analogues) 1
  • Radiotherapy or ionizing radiation 1
  • Environmental toxins such as benzene and its derivatives 1
  • Tobacco smoking 1
• Inherited predisposition is seen in one-third of pediatric MDS cases and less frequently in adults 1

Clinical Presentation

• Typically presents with signs and symptoms associated with cytopenias: 2
  • Anemia (fatigue, weakness)
  • Thrombocytopenia (bleeding, bruising)
  • Neutropenia (infections)
• Presentation is often insidious and discovered during routine blood tests 2

Diagnostic Criteria

MDS diagnosis is based on:

• Persistent peripheral blood cytopenias 1
• Bone marrow examination showing dysplastic features in ≥10% of cells in one or more cell lineages 1
• Common dysplastic features include: 1
  • Peripheral blood: Pseudo Pelger-Huet cells, abnormal chromatin clumping in granulocytes, giant platelets, anisocytosis, poikilocytosis in red cells
  • Bone marrow: Megaloblastoid changes in erythropoiesis, micromegakaryocytes, nuclear abnormalities, hypogranulation in granulocytes

Classification

• Historically referred to as oligoblastic leukemia, refractory anemia, smoldering acute leukemia, or preleukemia 1
• The French-American-British (FAB) classification was widely used since 1982 1
• The World Health Organization (WHO) classification is now the standard, with modifications including: 1
  • Lowering the threshold for diagnosing acute myeloid leukemia from 30% blasts to 20% blasts
  • Creating a category of MDS/myeloproliferative disorders for conditions like chronic myelomonocytic leukemia

Risk Stratification

• Prognosis is determined using scoring systems such as the International Prognostic Scoring System (IPSS) and the Revised IPSS (IPSS-R) 1, 3
• Key prognostic factors include: 1
  • Bone marrow cytogenetics
  • Percentage of bone marrow blasts
  • Number and severity of cytopenias
  • Age and gender
• Patients are categorized into lower risk (better prognosis) and higher risk (worse prognosis) groups 1
• Lower-risk MDS patients have a median survival of approximately 3-10 years, while higher-risk patients have a median survival of less than 3 years 2

Related Conditions

Several related conditions have been defined: 1

• ICUS (Idiopathic Cytopenias of Uncertain Significance): Mild cytopenias with no or mild dysplasia, <5% blasts, no clonal markers 1
• IDUS (Idiopathic Dysplasia of Unknown Significance): Dysplasia without significant cytopenias 1
• CHIP (Clonal Hematopoiesis of Indeterminate Potential): No significant cytopenias, presence of MDS-related mutations 1
• CCUS (Clonal Cytopenias of Uncertain Significance): Cytopenias with MDS-related mutations but minimal dysplasia 1

MDS represents a spectrum of myeloid disorders with variable clinical courses and outcomes, requiring individualized risk assessment and treatment approaches based on disease characteristics and patient factors.