Myelodysplastic syndrome (ORPHA:52688)
A group of myeloid hemopathies characterized by blood cytopenias, marrow dysplasia and a high risk of progression to acute myeloid leukemia (AML).
Epidemiology
The annual incidence is 1/17,000-25,000 people, with a median age at diagnosis of 70 years. Only 5-10% of patients are diagnosed below the age of 50.
Clinical description
Clinical symptoms are consequences of blood cytopenias, mainly anemia (e.g. fatigue, dyspnea, possible angina, etc.), and less often of thrombocytopenia (spontaneous bleeding) or neutropenia (bacterial or less often fungal infections).
Etiology
The etiology is unknown in 80% of the cases. In the remaining 20% it has either acquired causes (previous treatment with chemo or radiotherapy, occupational exposure to benzene derivatives or ionizing radiation) or inherited causes, such as inherited gene point mutations mainly in DDX41, GATA2, RUNX, and telomerase genes, or DNA instability (Fanconi anemia patients are prone to develop MDS).
Diagnostic methods
Blood count reveals aregenerative anemia, which is often macrocytic, with or without neutropenia and thrombocytopenia. Cytological/ Histological analysis of bone marrow aspirate or biopsy generally reveals hypercellularity, with dysplasia in one to three myeloid lineages, without (<5%) or with (5-20%) excess of blasts. Cytogenetics of bone marrow show acquired clonal abnormality in 50 % of the cases, especially chromosome loss (-7, del 5q, del 20q) or gain (+8). Marrow cell mutations analysis by NGS method reveals at least one acquired mutation in myeloid genes panel in 90% of the cases especially in spliceosome genes (SF3B1,SRSF2), epigenetic genes (TET2, DNMT3a, ASXL1), RUNX1, or TP53.
Differential diagnosis
The differential diagnosis includes other bone marrow failures such as aplastic anemia, AML, or peripheral and clonal hematopoiesis in the elderly.
Management and treatment
Management and treatment depends on the prognostic score of patients in the revised International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-R), recently improved by the addition of acquired mutations (IPSS-M). Higher risk MDS are treated with allogeneic bone marrow transplantation when possible, otherwise with hypomethylating agents (azacytidine, decitabine), and less often chemotherapy. Lower risk MDS patients receive treatment for anemia with erythropoietin or derivatives, or other drugs in specific cases (lenalidomide in case of 5q deletion; Luspatercept in MDS with ringed sideroblasts).
Prognosis
MDS may progress into AML in ~30% of patients. The prognosis differs depending on a set of criteria scored by the IPSS-R and IPSS-M, including the number and importance of cytopenias, marrow blast percentage, and marrow cytogenetic abnormalities. This score separates schematically patients into lower risk (mainly characterized by anemia and less often thrombocytopenia) and higher risk (with generally severe cytopenias, including also neutropenia) of progression to AML, into five (IPSS-R) or six (IPSS-M) categories going from very low risk (2.8% risk of transformation into AML by 4 years) to very high risk (42.8% risk of transformation into AML by 4 years).

                            Last update: 
                            July 2023


                            - Expert reviewer(s): 
                            Pr Pierre FENAUX | EuroBloodNet*


                                * European Reference Network