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Updated ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of MDS

Feb 25, 2021

The European Society for Medical Oncology (ESMO) Guidelines Committee issued an update of their Clinical Practice Guidelines for myelodysplastic syndromes (MDS) in November 2020, which was published in the February 2021 edition of Annals of Oncology.1

Below, we highlight the key recommendations from the ESMO Guidelines Committee regarding the diagnosis, staging, treatment, and follow-up of MDS.

Diagnosis and pathology/molecular biology

  • Diagnosis should be based on blood count, bone marrow aspirate, and bone marrow karyotype, with histology of bone marrow trephine biopsies strongly recommended.
    • In blood film, 200 cells should be reviewed per slide, and 500 cells in bone marrow.
    • Marrow blast count (including agranular blasts, myeloblasts, and promonocytes but not promyelocytes) must be calculated.
    • Staining for iron with Prussian blue (Perls stain) is to be carried out in lower-risk MDS to verify the presence of ring sideroblasts.
  • Cytogenetics on at least two different cell cultures, at 24 and 48 hours, is recommended.
    • Chromosome banding analysis should be performed on 20–25 metaphase cells, with complex abnormalities defined as ≥ 3 independent abnormalities in at least two metaphases.
    • In cases of normal karyotype or an insufficient number of metaphases, fluorescence in situ hybridization (FISH) with probes for 5q13, cen7, 7q31, cen8, TP53, 20q, and cenY is favored.
  • Molecular analysis by next generation sequencing can be used to demonstrate clonality where blood and marrow tests are inconclusive, however molecular profiling is not considered helpful for clinical management decisions apart from the following exceptions:
    • SF3B1 mutation in lower-risk MDS is associated with a higher likelihood to respond to luspatercept treatment.
    • TP53 mutation in lower-risk MDS correlates with an increased risk of leukemic transformation and shorter duration of response to lenalidomide.
  • If performed by experts and according to published guidelines,2 flow cytometry of blood and marrow cells can assist with diagnosis.
  • Classification should follow the World Health Organization (WHO) criteria.3
    • It was noted that the presence of del(5q), and not morphological criteria, defines del(5q) MDS, therefore cytogenic analysis is essential.

Staging and risk assessment

  • The revised International Prognostic Scoring System (IPSS-R) is highly recommended for treatment planning, incorporating marrow blast percentage, number and extent of cytopenias, and cytogenetic abnormalities.
  • The prognostic value of somatic mutations in treatment decisions is yet to be confirmed, except for the following:
    • TP53 mutation in patients with del(5q).
    • SF3B1 in patients with < 5% blasts.
    • IDH1/2 mutations.


The committee supported following the International Working Group recommendations4 when defining response criteria, including complete and partial response and progression.

Treatment of higher-risk MDS patients

  • Evaluation for allogeneic hematopoietic stem cell transplant (allo-HSCT) eligibility at diagnosis and during disease course is suggested for all patients ≤ 70 years old, or > 70 years if very fit.
  • In fit patients ≤ 70 years with a donor, chemotherapy or administration of a hypomethylating agent (HMA) prior to allo-HSCT are to be considered.
  • In patients not immediately eligible for allo-HSCT or without a donor, acute myeloid leukemia-like chemotherapy treatment or azacitidine (an HMA) should be initiated if there are no unfavorable cytogenetics and > 10% marrow blasts.
    • The recommended schedule is subcutaneous azacitidine 75 mg/m2/day for 7 days, every 28 days, for a minimum of six courses, although a ‘5-2-2’ regimen is acceptable if easier.
  • In very frail patients, supportive care should be provided, with red blood cell (RBC) transfusions and antibiotics as required.

Treatment of lower-risk MDS patients

  • It was noted that the main priority in patients with lower-risk MDS is treatment of cytopenias and improvement in quality of life.

Treatment of anemia

  • Symptomatic anemia (hemoglobin < 10g/dL) should be treated with chronic RBC transfusions.
  • In patients without del(5q), erythropoiesis-stimulating agents are recommended in the first line, with granulocyte colony-stimulating factor (G-CSF) to improve efficacy.
    • Antithymocyte globulin, with or without cyclosporine, can be discussed as a second-line treatment in patients < 65 years old with favorable features such as normal karyotype, no excess blasts, and HLA-DR15 genotype.
    • Luspatercept is recommended in patients with RBC transfusion-dependent MDS with ring sideroblasts or with SF3B1 mutation refractory to erythropoiesis-stimulating agents.
    • HMAs can be used, although they are not approved in Europe.
  • In patients with del(5q), lenalidomide is recommended at a dose of 10 mg/day for 3 weeks, every 4 weeks, however blood counts should be closely observed, and dose reduction and G-CSF considered if needed.
    • Patients who additionally have a TP53 mutation should be monitored carefully, including regular bone marrow assessments, and discussions around HMAs and allo-HSCT are suggested due to their poor prognosis.

Treatment of neutropenia and thrombocytopenia

  • G-CSF can assist in improving neutropenia and are suitable for use alongside antibiotics.
  • Thrombopoietin receptor agonists, such as romiplostim and eltrombopag, can currently only be used within clinical trials and registries in patients with < 5% blasts for the treatment of thrombocytopenia.

Supportive care and chelation therapy in MDS

All patients are likely to require supportive care at some point, and therefore access to psychosocial support and patient support groups should be provided. Key points on supportive care and chelation therapy highlighted in the updated guidelines were:

  • A sufficiently high hemoglobin threshold for RBC transfusions is important (at least 8 g/dL, and up to 9–10 g/dL in patients with comorbidities or poor functional tolerance), with transfusion over multiple days if necessary.
  • Prophylactic platelet transfusions are not recommended, nor are prophylactic antibiotics and/or G-CSF in the case of neutropenia, although broad-spectrum antibiotics should be initiated rapidly if fever or symptoms of infection are present.
  • Short-term use of G-CSF should be considered during severe infections.
  • Transfusion iron overload requires iron chelation therapy, particularly in allo-HSCT candidates.
    • Oral iron chelators and parenteral deferoxamine can be useful, although it was noted that deferasirox should not be used in patients with renal failure and deferiprone is not approved for use in MDS.

Personalized medicine

  • At present, the IPSS-R provides the basis for current treatment recommendations, and prognostic factors are not considered predictive of therapeutic efficacy.
  • Factors such as the patient’s age, performance status, comorbidities, frailty, and wishes should be considered prior to decision making with regards to treatment.


  • It was confirmed that the main aim of patient follow-up is to detect worsening cytopenias with regular blood counts.
  • If symptoms of infection occur, rapid onset of broad-spectrum antibiotics is warranted.
  • Bone marrow analysis is not currently performed regularly, although it is required upon detection of worsening cytopenias or circulating blasts.

  1. Fenaux P, Haase D, Santini V, et al. Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(2):142-156. DOI: 1016/j.annonc.2020.11.002
  2. Duetz C, Westers TM, van de Loosdrecht AA. Clinical implication of multi-parameter flow cytometry in myelodysplastic syndromes. Pathobiology. 2019;86(1):14-23. DOI: 1159/000490727 Top of Form
  3. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. DOI: 1182/blood-2016-06-721662
  4. Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419-25. DOI: 1182/blood-2005-10-4149