Myelodysplastic Syndromes

Last updated by Peer reviewed by Dr Hayley Willacy, FRCGP
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Synonyms: myelodysplasia, dysmyelopoiesis syndrome, pre-leukaemia

The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant haematopoietic disorders characterised by dysplastic changes in one or more cell lineages, ineffective haematopoiesis and a variable predilection to development of acute myeloid leukaemia (AML)[1] .

The bone marrow becomes hypercellular or hypocellular with disordered growth and maturation of a clonal proliferation of abnormal cells. This causes peripheral blood cytopenias due to insufficient haematopoiesis among healthy marrow cells, affecting the myeloid (white cells), erythroid (red cells) and megakaryocyte (platelets) lines. The degree to which each cell line is affected is very variable. The disease course of myelodysplastic syndromes is highly variable, ranging from indolent to aggressive with swift progression to AML.

About 10% of MDS are secondary, most often due to radiotherapy or chemotherapy for cancer. The time from treatment of a primary malignancy (particularly prostate, breast, bladder, lung or non-Hodgkin's lymphoma) to the development of MDS is about five years. A small number of myelodysplastic syndrome cases are due to occupational exposure to radiation, benzene or other organic solvents. Secondary MDS have a worse prognosis than primary MDS[2] .

  • The incidence of MDS is approximately 3.7/100,000 population/year. It is predominantly a disease of the elderly (median age at diagnosis 75.7 years)[1] . ars .
  • The overall prevalence of the syndromes appears to be increasing due to an ageing population and better diagnosis[3] .
  • MDS is more common in men and in smokers[2] .

Risk factors

  • Myelodysplastic syndrome is mainly a disease of older people.
  • Previous cancer therapy including radiotherapy, alkylating agents (peak 4-10 years after therapy), epipodophyllotoxins (peak within five years of therapy), topoisomerase II inhibitors or colony-stimulating factors used to stimulate marrow function during chemotherapy[4] .
  • Prolonged use of alkylator therapy for other illnesses - eg, rheumatological disease.
  • Environmental toxins, especially benzene and other organic solvents, smoking, petroleum products, fertilisers, semi-metal, stone dusts and cereal dusts.
  • More unusually, it may be associated with other genetically associated diseases - eg, Shwachman-Diamond syndrome, Fanconi's anaemia and neurofibromatosis type 1, which are all associated with an increased risk[5, 6] .


  • Variable in severity and is usually two or more distinct populations of red cells with normal or a hypochromic microcytic red cells and macrocytes.
  • An unexplained macrocytic anaemia with no evidence of megaloblastosis and/or a mild thrombocytopenia or neutropenia may be the initial indicator of a problem and precede symptomatic illness or a definitive haematological diagnosis of MDS by several years.
  • Typically in an older patient presenting with symptoms of chronic anaemia - eg, fatigue and exertional dyspnoea.
  • There may be worsening of pre-existing pathology, due to presence of anaemia, particularly cardiac problems - eg, angina, congestive cardiac failure.


  • Neutropenia often occurs and is variable in severity.
  • If granulocyte depletion occurs, patients may present with recurrent or unusual infections or overwhelming sepsis.


  • The platelet count is often decreased with abnormal platelets.
  • If thrombocytopenia is present, patients may notice petechiae, bruising, nosebleeds or bleeding from gums after brushing teeth.
  • It may present as a bleeding diathesis with haemoptysis, haematuria or rectal bleeding.

There may be constitutional symptoms such as anorexia, weight loss, sweats and fevers, which occur in more advanced disease.


  • Examination should seek evidence of petechiae and ecchymoses (check under waistbands of clothing or other pressure points).
  • Inspect conjunctivae to look for evidence of anaemia.
  • Look for other clinical evidence of anaemia, such as cardiac failure or tachycardia.
  • Examine the mouth for evidence of anaemia and infections such as candidiasis.
  • Splenomegaly and lymphadenopathy are uncommon[2] .

The diagnosis of MDS is typically made by excluding other non-MDS causes of cytopenias in the presence of some combination of dysplastic cell morphology, increased marrow blasts and a karyotypic abnormality .

  • FBC and blood film:
    • Anaemia, either normocytic or macrocytic.
    • There may be cytopenias affecting the other cell lines: there may be neutropenia, thrombocytopenia, neutrophilia, monocytosis, thrombocytosis.
    • Blood film characteristically shows dimorphic red cells, Pappenheimer bodies, basophilic stippling, dysplasia evidenced as erythrocytes with anisocytosis (varying sizes) and poikilocytosis (abnormal shape). Platelets may be large or hypogranular.
  • Serum ferritin, vitamin B12 and red blood cell folate levels are usually normal. Check renal function tests, LFTs; CXR and ECG to assess comorbidity.
  • Bone marrow aspirate/biopsy plus cytogenetics - typically showing hypercellular marrow due to ineffective haematopoiesis and commonly showing megaloblastoid erythropoiesis.
  • Cytogenetic marrow studies show chromosomal abnormalities in 48-64% of cases, depending on series.
  • More advanced cytogenetic analyses, such as fluorescent in situ hybridisation, can reveal abnormalities in up to 79% of cases.
  • There are various clonal chromosomal abnormalities, including loss of part of a chromosome, monosomy or trisomy, usually affecting chromosomes 5, 7 and 8.
  • Chronic myelomonocytic leukaemia (monocytosis with >1,000 cells/μl and trilineage dysplasia) appears to be an overlap condition between MDS and myeloproliferative disorders.
  • MDS also appears to show overlap features with severe aplastic anaemia and paroxysmal nocturnal haemoglobinuria.


  • The classification of MDS is continuously evolving[9] . Every new validated classification reflects better understanding of myelodysplastic syndrome, its pathogenesis and prognosis[10] .
  • The traditional classification is the French-American-British (FAB) classification. However, it is thought that this system is inadequate in terms of clinical homogeneity and outlook within the groups. It is no longer in general use.
  • An International Prognostic Scoring System (IPSS) and a World Health Organization (WHO) classification have now been devised, which assess the type and extent of cytogenetic marrow abnormality and the cell lines affected. The WHO is now the recommended classification system[8] . The original IPSS has now been replaced by a revised version which takes into account more cytogenetic data (IPSS-R).

The WHO classification system[8]

  • Myelodysplastic syndrome (MDS) with single lineage dysplasia.
  • MDS with ring sideroblasts (MDS-RS).
  • MDS with multi-lineage dysplasia (MDS-MLD).
  • MDS with excess blasts (MDS-EB-1), with 5% to 9% blasts in the bone marrow.
  • MDS with excess blasts (MDS-EB-2), with 10% to 19% blasts in the bone marrow.
  • MDS with isolated del(5q)MDS, unclassifiable (MDS-U).

In addition, there are overlap syndromes included in the WHO classification, including myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) and myelodysplastic/myeloproliferative neoplasm, unclassifiable.

The IPSS-R is based on the percentage of bone marrow blast cells and the number of cytopenias to calculate the risk score. Patients can be categorised into one of four groups: low-risk, intermediate-1 and intermediate-2 risks and high-risk.

Clinical variants of MDS

There are clinical variants identified that do not neatly fall into the classification system. These include:

  • Chronic myelomonocytic leukaemia (CMML), which is the fifth element in the FAB classification but is an MDS/myeloproliferative disease (MPD) condition according to the WHO classification (see next section).
  • 5-q syndrome - a clinically distinct form of MDS that follows a more indolent course and predominantly occurs in female patients.
  • Pure sideroblastic anaemia - in these patients, dysplasia is confined to erythropoietic cells and is associated with improved survival rates.
  • Secondary MDS - the incidence of this is increasing due to successful chemotherapy in a greater proportion of the population. The prognosis is worse than with de novo disease.
  • Hypoplastic MDS - this occurs in fewer than 15% of cases and may be difficult to distinguish from aplastic anaemia. Diagnosis is based on investigations as above and its significance is that it may respond to immune therapy.
  • Fibrotic MDS - although almost half the patients have an element of bone marrow fibrosis, this is marked in about 15% of patients (more commonly in secondary MDS); it is associated with rapid deterioration.

Myelodysplastic/myeloproliferative diseases (MDS/MPD)

This is a category of disease created within the WHO classification of myeloid neoplasms for a group of disorders which have both dysplastic and proliferative features at diagnosis and which are therefore difficult to designate as either myelodysplastic or myeloproliferative. They include:

  • CMML.
  • Atypical chronic myeloid leukaemia.
  • Juvenile myelomonocytic leukaemia.
  • Unclassifiable MDS/MPD.

The management of MDS is constantly evolving with new agents being trialled and licensed on a regular basis. Patients with low-risk, indolent MDS may require no active management but are usually followed up in a haematology clinic. Although high-dose chemotherapy may cure a small subset of patients with MDS, allogeneic haematopoietic cell transplantation is the only currently available modality that is curative in a large proportion of patients[11] .

In lower-risk MDS, the risk of AML progression is smaller and survival longer than in higher-risk MDS, with about one half of elderly patients dying from causes other than the consequences of MDS or AML. In lower-risk MDS, the main priority is generally the treatment of cytopenias, mainly of anaemia and improving quality of life.

Anaemia often eventually requires repeated red blood cell transfusions, leading to potential iron overload. However, iron chelation therapy is not routinely recommended for MDS patients with transfusional iron overload. Triggers for chelation therapy may include more than 20 units of red cells transfused, or serum ferritin >1000 μg/L in patients for whom continuing red cell transfusion is predicted.

Supportive care

Anaemia and thrombocytopenia

  • In symptomatic anaemia, in those with anaemia-related cardiovascular disease, bleeding episodes and/or high risk of significant bleeds, treatment is supportive blood and platelet transfusions.
  • Many patients can live for prolonged periods with regular blood/platelet transfusions; patients who receive long-term recurrent transfusion require monitoring of their iron status (ferritin levels) and iron chelation therapy (eg, with desferrioxamine) if necessary, such as if the patient receives more than 20 units of packed red blood cells.
  • Erythropoietin ± granulocyte colony-stimulating factor (G-CSF) for the treatment of symptomatic anaemia may improve the quality of life, providing a more stable haemoglobin value compared with the cyclical fluctuations of blood transfusions[1] . These treatments are efficacious and safe for the treatment of anaemia associated with MDS . However, increased blood parameters do not necessarily improve survival.


  • Neutropenic sepsis should be treated promptly with empirical broad-spectrum antibiotics but there is no evidence supporting the routine use of prophylactic anti-infective agents.
  • G-CSF treatment of neutropenia, particularly where there are recurrent or antibiotic-resistant infections.

High-intensity therapy: chemotherapy

A large number of different forms of chemotherapy have been tried for myelodysplastic syndrome, including those used to treat AML but results are generally disappointing[12] . Generally, if the patient is otherwise reasonably well, more aggressive treatment can be envisaged. More commonly, the patient is elderly or has some significant comorbidity, in which case less aggressive treatment is usually considered.

  • Fludarabine phosphate, cytarabine and G-CSF (FLAG) have been used with success in de novo RAEBt.
  • Modern DNA anti-methylating agents (azacitidine, decitabine), farnesyl transferase inhibitors (lonafarnib, tipifarnib) and immunomodulators such as lenalidomide (a thalidomide analogue effectively used in the treatment of 5-q syndrome)[9] have been shown to have some efficacy in preventing/slowing progression of low-risk or early MDS and decreasing the need for transfusion[13] .
  • The National Institute for Health and Care Excellence (NICE) recommends azacitidine as a treatment option for adults who are not eligible for haematopoietic stem cell transplantation and have[14] :
    • Intermediate-2 and high-risk MDS according to the IPSS; or
    • CMML with 10-29% marrow blasts without MDP; or
    • AML with 20-30% blasts and multi-lineage dysplasia, according to the WHO classification.
  • Lenalidomide is recommended by NICE as an option for treating transfusion-dependent anaemia caused by low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate[15] .
  • Complications of anaemia, thrombocytopenia and low white cell count.
  • Myelofibrosis may develop and cause increased transfusion dependence and disease progression.
  • Patients are, therefore, at risk of transfusional iron overload and iron chelation therapy has been shown to improve organ function and survival[16, 17] .
  • Transformation to AML.
  • Splenomegaly may lead to splenic rupture and intraperitoneal haemorrhage.

The natural course of MDS is very variable, depending on several factors, including cytogenetics and severity of cytopenia. Patients categorised by the IPSS-R system as very high-risk have a median overall survival rate of 0.8 years compared with those in the very low- risk category who have a median overall survival rate of 8.8 years.

Patients with isolated 5q deletion may have longer survival than other types of MDS, One study noted five-year survival of 40% if they did not receive treatment and 54% if they received treatment.

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Further reading and references

  1. British Society for Haematology guidelines for the management of adult myelodysplastic syndromes; British Journal of Haematology, 2021

  2. Barzi A, Sekeres MA; Myelodysplastic syndromes: a practical approach to diagnosis and treatment. Cleve Clin J Med. 2010 Jan77(1):37-44.

  3. Corey SJ, Minden MD, Barber DL, et al; Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007 Feb7(2):118-129.

  4. Hershman D, Neugut AI, Jacobson JS, et al; Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst. 2007 Feb 799(3):196-205.

  5. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (November 2020)

  6. Myers KC, Furutani E, Weller E, et al; Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicentre, retrospective, cohort study. Lancet Haematol. 2020 Mar7(3):e238-e246. doi: 10.1016/S2352-3026(19)30206-6. Epub 2019 Dec 23.

  7. Myelodysplastic Syndromes Treatment (PDQ(R)); Health Professional Version

  8. Dotson JL, Lebowicz Y; Myelodysplastic Syndrome

  9. Maniatis A; Progress in the treatment of myelodysplastic syndromes. Blood Transfus. 2008 Oct6(4):180-1.

  10. Komrokji RS, Bennett JM; Evolving classifications of the myelodysplastic syndromes. Curr Opin Hematol. 2007 Mar14(2):98-105.

  11. Deeg HJ; Hematopoietic cell transplantation for myelodysplastic syndrome. Am Soc Clin Oncol Educ Book. 2015:e375-80. doi: 10.14694/EdBook_AM.2015.35.e375.

  12. Steensma DP; Myelodysplastic Syndromes: Diagnosis and Treatment. Mayo Clin Proc. 2015 Jul90(7):969-83. doi: 10.1016/j.mayocp.2015.04.001.

  13. Larson RA; Myelodysplasia: when to treat and how. Best Pract Res Clin Haematol. 200619(2):293-300.

  14. Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia; NICE Technology Appraisal Guidance, March 2011

  15. Lenalidomide for treating myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality; NICE Technology Appraisal Guidance, September 2014 - last updated June 2019

  16. List AF; Iron overload in myelodysplastic syndromes: diagnosis and management. Cancer Control. 2010 Jan17 Suppl:2-8.

  17. Leitch HA; Optimizing therapy for iron overload in the myelodysplastic syndromes: recent Drugs. 2011 Jan 2271(2):155-77. doi: 10.2165/11585280-000000000-00000.