MYELODYSPLASTIC SYNDROMES (MDS)
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.
|Name||WHO Estimated Proportion of Patients with MDS||Peripheral Blood: Key Features||Bone Marrow: Key Features|
|Refractory cytopenias with unilineage dysplasia (RCUD):|
|Refractory anemia (RA)||10–20%||Anemia <1% of blasts||Unilineage erythroid dysplasia (in ≥10% of cells) <5% blasts|
|Refractory neutropenia (RN)||<1%||Neutropenia <1% blasts||Unilineage granulocytic dysplasia <5% blasts|
|Refractory thrombocytopenia (RT)||<1%||Thrombocytopenia <1% blasts||Unilineage megakaryocytic dysplasia <5% blasts|
|Refractory anemia with ring sideroblasts (RARS)||3–11%||Anemia||Unilineage erythroid dysplasia ≥15% of erythroid precursors are ring sideroblasts <5% blasts|
|Refractory cytopenias with multilineage dysplasia (RCMD)||30%||Cytopenia(s) <1% blasts||Multilineage dysplasia ± ring sideroblasts <5% blasts|
|No Auer rods||No Auer rods|
|Refractory anemia with excess blasts, type 1 (RAEB-1)||40%||Cytopenia(s) <5% blasts||Unilineage or multilineage dysplasia|
|No Auer rods|
|Refractory anemia with excess blasts, type 2 (RAEB-2)||Cytopenia(s) 5–19% blasts||Unilineage or multilineage dysplasia 10–19% blasts|
|± Auer rods||± Auer rods|
|MDS associated with isolated del(5q)||Uncommon||Anemia||Isolated 5q31 chromosome deletion|
|Normal or high platelet count <1% blasts||Anemia; 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)||?|
Does not fit other categories
If no dysplasia, MDS-associated karyotype
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 1||2 or 3|
|Risk Group Scores||Score|
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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