These are clonal abnormalities of marrow cells characterized by varying degrees of cytopenias affecting one or more cell lines. The World Health Organization (WHO) classification of myelodysplastic syndromes is shown in Table 65-3. Other terms that have been used to describe one or more of the entities include preleukemia and oligoblastic leukemia.

NameWHO Estimated Proportion of Patients with MDSPeripheral Blood: Key FeaturesBone Marrow: Key Features
Refractory cytopenias with unilineage dysplasia (RCUD):
 Refractory anemia (RA)10–20%Anemia <1% of blastsUnilineage erythroid dysplasia (in ≥10% of cells) <5% blasts
 Refractory neutropenia (RN)<1%Neutropenia <1% blastsUnilineage granulocytic dysplasia <5% blasts
 Refractory thrombocytopenia (RT)<1%Thrombocytopenia <1% blastsUnilineage megakaryocytic dysplasia <5% blasts
Refractory anemia with ring sideroblasts (RARS)3–11%AnemiaUnilineage erythroid dysplasia ≥15% of erythroid precursors are ring sideroblasts <5% blasts
  No blasts 
Refractory cytopenias with multilineage dysplasia (RCMD)30%Cytopenia(s) <1% blastsMultilineage dysplasia ± ring sideroblasts <5% blasts
  No Auer rodsNo Auer rods
Refractory anemia with excess blasts, type 1 (RAEB-1)40%Cytopenia(s) <5% blastsUnilineage or multilineage dysplasia
  No Auer rods 
Refractory anemia with excess blasts, type 2 (RAEB-2) Cytopenia(s) 5–19% blastsUnilineage or multilineage dysplasia 10–19% blasts
  ± Auer rods± Auer rods
MDS associated with isolated del(5q)UncommonAnemiaIsolated 5q31 chromosome deletion
  Normal or high platelet count <1% blastsAnemia; hypolobated megakaryocytes <5% blasts
Childhood MDS, including refractory cytopenia of childhood (provisional) (RCC) 1 %Pancytopenia<5% marrow blasts for RCC
   Marrow usually hypocellular
MDS, unclassifiable (MDS-U)?


≤1% blasts

Does not fit other categories


<5% blasts

If no dysplasia, MDS-associated karyotype

Note: If peripheral blood blasts are 2–4%, the diagnosis is RAEB-1 even if marrow blasts are <5%. If Auer rods are present, the WHO considers the diagnosis RAEB-2 if the blast proportion is <20% (even if <10%), AML if at least 20% blasts. For all subtypes, peripheral blood monocytes are <1 × 109/L. Bicytopenia may be observed in RCUD subtypes, but pancytopenia with unilineage marrow dysplasia should be classified as MDS-U. Therapy-related MDS (t-MDS), whether due to alkylating agents, topoisomerase II (t-MDS/t-AML) in the WHO classification of AML and precursor lesions. The listing in this table excludes MDS/myeloproliferative neoplasm overlap categories, such as chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, and the provisional entity RARS with thrombocytosis.
Abbreviation: MDS, myelodysplastic syndrome.

Incidence and Etiology

About 3000 cases occur each year, mainly in persons >50 years old (median age, 68). As in AML, exposure to benzene, radiation, and chemotherapeutic agents may lead to MDS. Chromosome abnormalities occur in up to 80% of cases, including deletion of part or all of chromosomes 5, 7, and 9 (20 or 21 less commonly) and addition of part or all of chromosome 8. Mutations in genes involved in RNA splicing such as SF3B1 have a more favorable outcome; mutations in genes often involve in AML such as RUNX and ASXL1 have poorer prognosis.

Clinical and Laboratory Features

Symptoms depend on the affected lineages, 85% of pts are anemic, 50% have neutropenia, and about one-third have thrombocytopenia. The pathologic features of MDS are a cellular marrow with varying degrees of cytologic atypia including delayed nuclear maturation, abnormal cytoplasmic maturation, accumulation of ringed sideroblasts (iron-laden mitochondria surrounding the nucleus), uni- or bilobed megakaryocytes, micromegakaryocytes, and increased myeloblasts. Table 65-3 lists features used to identify distinct entities. Prognosis is defined by marrow blast %, karyotype, and lineages affected. The International Prognostic Scoring System is shown in Table 65-4.

Prognostic Variable Score Value
Bone marrow blasts (%)<5%5–10% 11–20%21–30%
Cytopeniab (lineages affected)0 or 12 or 3   
Risk Group ScoresScore    
aGood, normal, -Y, del(5q), del(20q); poor, complex (≥3 abnormalities) or chromosome 7 abnormalities; intermediate, all other abnormalities.
bCytopenias defined as Hb <100 g/L, platelet count <100,000/μL, absolute neutrophil count <1500/μL.


Allogeneic bone marrow transplantation is the only curative therapy and may cure 60% of those so treated. However, the majority of pts with MDS are too old to receive transplantation. 5-Azacytidine (75 mg/m2 daily × 7, q 4 weeks) can delay transformation to AML by 8–10 months. Decitabine (15 mg/m2 by continuous IV infusion, q8h daily × 3, q 6 weeks) may induce responses lasting a median of 1 year in 20% of pts. Lenalidomide (10 mg/d), a thalidomide analogue with fewer central nervous system effects, causes a substantial fraction of pts with the 5q– syndrome to become transfusion-independent. Pts with low erythropoietin levels may respond to erythropoietin, and a minority of pts with neutropenia respond to granulocyte colony-stimulating factor. Supportive care is the cornerstone of treatment.


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