Myelodysplastic Syndromes: New Methods of Diagnosis, Prognostication, and Treatment

Abstract

Background: Myelodysplastic syndromes (MDS) are malignant diseases arising from hematopoietic stem cells. Their overall incidence is 4 cases per 100 000 persons per year, and they are usually diagnosed when evaluating cytopenia. The median survival time is three years. Myelodysplastic syndromes take a variable course; one-quarter of patients go on to develop acute leukemia.

Methods: This review is based on publications retrieved by a selective search of the literature from 2013 to 2022, including relevant guidelines, in the PubMed database. The time period was chosen to reflect developments since the publication of the latest EHA guidelines in 2013.

Results: The gold standard of diagnosis is cytomorphology of the blood and bone marrow, supplemented by banding cytogenetics, histomorphology, and somatic mutation analyses. The new classification proposed by the WHO incorporates the molecular and cytogenetic findings. The Molecular International Prognostic Scoring System (IPSS-M), which takes somatic mutations into account, is now available as an aid to prognostication. Quality of life evaluation with standardized instruments is helpful in many ways. Low-risk patients are treated supportively with erythrocyte transfusions and iron chelation therapy. Erythropoietin-a can be given to patients whose erythropoietin level is less than 200ng/mL, lenalidomide to those with a 5q deletion, and luspatercept to those with an SF3B1 mutation. High-risk patients should be evaluated as early as possible for allogeneic hematopoietic stem cell transplantation with curative intent. 5-azacytidine improves outcomes in patients for whom stem cell transplantation is not suitable.

Conclusion: Once a precise diagnosis has been established, new prognostic instruments such as the IPSS-M enable risk-adapted treatment based on the biological aspects of the patient's disease as well as his or her age and comorbidities.

Figure 1

Figure 1 Mean survival time according to WHO subtype in years; MDS, myelodysplastic syndrome

Figure 2

Therapy algorithm for patients with myelodysplastic syndrome and very low, low, or intermediate risk: approved = gray (erythropoietin-alpha, Exjade, lenalidomide, luspatercept) EPO, erythropoietin

Figure 3

Therapy algorithm for patients with myelodysplastic syndrome and intermediate risk (int-2), high risk or very high risk: approved gray (5-azazytidine,9 allogeneic stem cell transplantation)

eFigure 1

Survival curves of the different risk groups according to the IPSS-R. Mean survival of all patients 34 months, mean survival of IPSS-R risk groups: blue: “very low”: 98 months, green: “low“: 61 months, red: “intermediate“: 31 months, orange: “high“: 23 months, brown: “very high risk”: 10 months, p<0.00005, (n= 2694, data from the Düsseldorf MDS Registry).

eFigure 2

Cumulative risks for AML transition of the various risk groups according to IPSS-R, blue: “very low”: green: “low“, red: “intermediate“, orange: “high“, brown: “very high“, p<0.00005 (n = 2694, data from the Düsseldorf MDS Registry). AML, acute myeloid leukemia; MDS, myelodysplastic syndromes

eFigure 3

Survival curves of patients with “intermediate”, “high” and “very high risk” after IPSSR, according to therapy, mean survival time of all patients 20 months, mean survival time with “best supportive care” 18 months, with induction chemotherapy 18 months, with therapy with 5-azacytidine, 24 months and with allogeneic stem cell transplantation 96 months, p<0.0005 (n = 887, data from the Düsseldorf MDS Registry). BSC, best supportive care; MDS, myelodysplastic syndromes