Description

Myelodysplastic syndromes (MDSs) constitute a heterogeneous group of acquired hematopoietic stem-cell disorders characterized by cytologic dysplasia in the bone marrow and blood and by various combinations of anemia, neutropenia, and thrombocytopenia:

• The natural progression of disease evolves as cellular maturation becomes more arrested and blast cells accumulate. There is a overlap between arbitrary diagnostic subgroups.
• World Health Organization (WHO) classification (1):
  • Refractory cytopenia with unilineage dysplasia:
    • Refractory anemia (RA); refractory neutropenia; refractory thrombocytopenia
    • <5% blasts and <15% ring sideroblasts in marrow; <1% blasts in blood
  • Refractory anemia with ring sideroblasts (RARS):
    • <5% blasts in marrow; ≥15% of erythroid precursors are ring sideroblasts; no blasts in blood
    • Also known as acquired idiopathic sideroblastic anemia
  • Refractory cytopenia with multilineage dysplasia:
    • Marked trilineage dysplasia, but without excess blasts in marrow; no Auer rods; <1% blasts in blood
  • Refractory cytopenia with multilineage dysplasia and ring sideroblasts
  • Refractory anemia with excess blasts-1 (RAEB-1):
    • 5–9% blasts in marrow; no Auer rods; <5% blasts in blood; <1,000 monocytes/mm³
  • RAEB-2:
    • 10–19% blasts in marrow; 5–19% blasts in blood; ±Auer rods; <1,000 monocytes/mm³
  • MDS associated with isolated del(5q) (2):
    • RA with erythroid hyperplasia, increased megakaryocytes with hypolobated nuclei, and normal or increased platelets; <5% blasts in marrow; <1% blasts in blood
  • Acute MDS with sclerosis:
    • RAEB with marked myelosclerosis
  • Chronic myelomonocytic leukemia (CMMoL or CMML) is now grouped with myelodysplastic/myeloproliferative disorders:
    • <20% blasts and promonocytes in marrow and blood with >1,000 monocytes/mm³
  • RAEB in transformation is now considered acute myeloid leukemia (AML):
    • 20–30% blasts in marrow; >20% blasts in blood
    • Incidence: 2:1 (female > male)
  • Therapy-related MDS (t-MDS) (3,4):
    • Seen 3–7 years after treatment with alkylating agents and/or radiotherapy
    • Evolves to AML over ~6 months
    • Classified by the WHO as therapy-related myeloid neoplasm
• System(s) affected: Hematologic; Lymphatic; Immunologic
• Synonym(s): Dysmyelopoietic syndrome; Hemopoietic dysplasia; Preleukemia; Smoldering or subacute myeloid leukemia

• Monosomy 7 syndrome
• Juvenile chronic myelogenous leukemia

Epidemiology

• Predominant age: Median age, >65 years; uncommon in children and young adults
• Predominant sex: Male = Female

Incidence
Apparent increased incidence (1–2/100,000/yr) in recent years may be due to improved diagnosis; incidence increases markedly with older age.

Risk Factors

• Primary MDS is associated with older age, occupational exposure to petroleum solvents (benzene, gasoline), and smoking.
• Secondary (therapy-related) MDS is associated with prior treatment with alkylating agents or radiotherapy.

• Most are clonal neoplasms by cytogenetics, G6PD isoenzyme analysis, or restriction fragment length polymorphism analysis.
• Mutations in RAS oncogene
• Mutations in RPS14 gene on chromosome 5q
• TET2 mutations

Commonly Associated Conditions

• Anemia
• Neutropenia
• Thrombocytopenia
• Pancytopenia
• Opportunistic infections
• Bleeding, bruising
• Sweet syndrome (neutrophilic dermatosis)