Abstract:
Myelodysplastic syndromes are a group of clonal bone marrow diseases, that are characterized by peripheral cytopenia, signs of dysplasia, ineffective hematopoiesis, increased blasts, and a frequent transition to acute myeloid leukemia. According to the WHO-classification, MDS is one of five subclasses of myeloid neoplasms besides to the acute myeloid leukemias, the myeloproliferative neoplasms, the myelodysplastic/myeloproliferative neoplasms and the myeloid/lymphatic neoplasms with eosinophilia and abnormal PDGFRA, PDGFRB or FGFR1.
Clinical picture:
With a mean age of 70 years, MDS is a disease of the elderly. The overall incidence is about 3-5/100'000/year; among the >70-year olds it is >20/100'000/year. It is a heterogenous group of diseases. The activity of these diseases increase with progressive signs of dysplasia (from 1 to 2 to 3 cell lines affected) and increasing blasts in the blood and bone marrow(from lacking up to 10-20%). Depending on the MDS-subtype (see below), the consequences of cytopenia (fatigue in anemia, bleeding in thrombocytopenia, infections in neutropenia) predominate in low malignancy MDS-types (MCUD, RARS, MDS 5q-), while in higher malignancy MDS-types (RAEB-1, RAEB-2) the transition to acute myeloid leukemia with reduced life expectancy is of higher significance.
| Mean survival rate (months) |
time to AML in 25% of patients (months) |
|
| RCUD/RARS/MDS 5q- | 99 | not reached |
| RCMD | 66 | 123 |
| RAEB-1 | 28 | 23 |
| RAEB-2 | 18 | 9 |
Clinical picture:
in the peripheral blood, one can find depending on the MDS-subtype (see below) one or more cytopenias (anemia, thrombocytopenia or neutropenia) as well as the release of myeloid blasts (lacking to <20%). Typical are signs of dysplasia in peripheral blood cells: poikilocytosis, anisocytosis and macrocytosis of erythrocytes, lacking or decreased granulation as well as abnormalities of nuclear segmentation (Pseudo-Pelger-Huët-anomaly) in neutrophils. In platelets, macrocytosis, anisocytosis, and abnormalities of granulation of thrombocytes are present.
Bone marrow:
Typically, the bone marrow is hypercellular. There are also hypocellular MDS-variants as well as subtypes with fibrosis of the bone marrow. The discrepancy between increased cellularity in the bone marrow and severe cytopenias in the peripheral blood as expression of an ineffective hematopoiesis is striking. Depending on the MDS-subtype, blasts are lacking or increased to a maximum of 20% . Signs of dysplasia of erythropoiesis, myelopoiesis or megakaryopoiesis are imperative for the diagnosis of MDS and at least 10% of the cells of one lineage must show signs of dysplasia.
Diagnosis:
Besides the exclusion of reactive cytopenias and the typical morphological findings in the bone marrow aspirate and biopsy, cytogenetics as well as hybridization methods (FISH/CGH) are of major importance to secure the diagnosis and to give a prognosis. Flow cytometric immunophenotyping will be of increasing importance in the diagnosis of MDS.
WHO-classification of myelodysplastic syndromes:
| Abbreviation | MDS-subtype | Blood | Bone marrow |
|---|---|---|---|
| RCUD - RA - RN - RT |
Refractory cytopenia with unilinear dysplasia
|
Unicytopenia or bicytopenia no or rare blasts (<1%) |
Dysplasias in ≥10% cells in one cell lineage <5% blasts <15% ringed sideroblasts |
| RARS | Refractory anemia with ringed sideroblasts | Anemia, no blasts | ≥15% ringed sideroblasts Exclusively erythroid dysplasias <5% blasts |
| RCMD | Refractory cytopenia with multilinear dysplasia | One or more cytopenias No or rare blasts (<1%) No Auer rods Monocytes <1.0 x 109/L |
Dysplasias in ≥10% cells in ≥2 cell lineages |
| RAEB-1 | Refractory anemia with excess of blasts-1 | One or more cytopenias <5% blasts No Auer rods Monocytes <1.0 x 109/L |
Unilinear or multilinear dysplasias 5-9% blasts No Auer rods
|
| RAEB-2 | Refractory anemia with excess of blasts-2 | One or more cytopenias 5-19% blasts Auer rods possible Monocytes <1.0 x 109/L |
Unilinear or multilinear dysplasias 10-19% blasts Auer rods possible |
| MDS-U | Unclassifiable MDS | One or more cytopenias ≤1% blasts |
Clear signs of dysplasia in <10% of cells of one or more lineages and simultaneous MDS-typical cytogenetics <5% blasts |
| MDS 5q- | MDS with isolated del(5q) | Anemia Normal or increased thrombocytes No or rare blasts (<1%) |
Cytogenetic with isolated del(5q) Number of megakaryocytes normal or increased with hypolobulated nuclei of megakaryocytes <5% blasts No Auer rods |