Myelodysplastic syndromes (MDS)

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-Hu√ęt-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
  • Refractory anemia
  • Refractory neutropenia
  • Refractory thrombocytopenia
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
<5% blasts
No Auer rods
Ringed sideroblasts present or lacking

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