Myelodysplastic Syndrome (MDS) (BSH 2013)


Heterogeneous group of malignant hematopoietic disorders, characterized by dysplastic changes in 1 or more cell lineages, ineffective hematopoiesis and a variable risk of developing AML

4 per 100,000 per year (>30/100,000/year of >70 y.o.)

All patients should be offered a review at a regional expert centre given rarity of disease.  


WHO 2016 Classification

mds who.png




  • Prior chemo/radiotherapy exposure

  • FHx of MDS/AML or pulmonary/liver fibrosis

  • Recurrent infection


  • Dysmorphic features

  • Splenomegaly, bruising, bleeding, infections, skin lesions


  • FBC, Film, Reticulocytes, LDH, Ferritin, B2M, Blood group and Antibody screen

  • Hep B/C, HIV


  • MGG stain with assessment of 500 cells inc. 30 megakaryocytes – dysplasia should be present in at least 10% of cells of relevant lineage

  • Flow cytometry optional – no specific immunophenotype

  • Iron stain (Prussian Blue / Perls) - >15% ring sideroblasts for MDS-RS

  • Reticulin stain

  • Cytogenetics – performed on at least 25 metaphases


Further Investigations to consider

  • Epo level

  • PNH screen

  • Fanconi anaemia screen

  • Mutational analysis if constitutional cause suspected

  • HLA typing of patient and siblings if transplant considered

  • Parvo, CMV

  • Red cell extended phenotyping if chronic transfusion expected

  • JAK2 if MPN/MDS overlap suspected


Prognosis – IPSS-R


IPSS-R designed for use at diagnosis

The WHO WPSS can be used at any time during the course of the disease



Prognosis - IPSS


Therapy is guided by IPSS (based on blast % / karyotype / No. of cytopenias) , not IPSS-R

Low risk patients = IPSS Low / Intermediate 1 (INT-1)

High risk patients = IPPS INT-2 / High

Source:  Blood Ref

Source: Blood Ref

Supportive Care



  • Irradiated products after ATG or transplant

  • Transfuse to correct symptomatic anaemia and improve QoL

  • Consider extended phenotyping for those on chronic transfusion programme


Neutropenia + Infection

  • GCSF in low risk disease with recurrent infections

  • Antifungal prophylaxis if receiving active treatment


Thrombocytopenia + Active bleeding

  • Routine prophylactic transfusion may be appropriate in recurrent bleeding

  • But not required in stable non-bleeding patients regardless of absolute count

  • TXA, esp for mucous membrane bleeding


Spiritual and Emotional health needs

  • Rare disease, difficult to understand, many treatments, poor outlook


Management of Low Risk MDS


General Approach

Discuss potentially eligible patients w/ allogeneic transplant team early after diagnosis, as early HSCT preferred

Non-transplant options include:

  • Supportive Care

  • ATG + Ciclosporin - consider in patients <60 y.o. with normal karyotype or trisomy 8

  • Lenalidomide - consider in 5q- and 1 or fewer other karyotypic abnormalities

  • Erythropoeitin - add GSCF in siderolblastic variants. Stop after 16 weeks if no response

Consider iron chelation in some low risk patients with a very good prognosis – Desferrioxamine preferred due to experience of use


5q- Syndrome

(Diagnostic note: One additional cytogenetic abnormality is allowed except for chromosome 7 abnormalities, which carry a very poor prognosis. Also, MDS-EB trumps 5q- diagnosis)

Typically presents as refractory anaemia in older women with macrocytosis, thrombocytosis and non-lobulated megakaryocytes (micromegakaryocytes).

Relatively indolent natural history.

Lenalidomide induces a durable transfusion independency, though patients ultimately relapse.

Even during complete cytogenetic response (CCyR) during lenalidomide therapy, morphology demonstrates persistence of non-lobated micomegakaryocytes.


Other Good Prognosis Cytogenetic Subtypes

SF3B1 mutation in MDS with Ring Sideroblasts and thrombocytopenia (MDS/MPN-RS-T)


Management of High Risk MDS


General Approach

Transplant eligible patients

  • Early HSCT - Precede by induction chemotherapy if >10% blasts or hypercellular bone marrow

Transplant ineligible patients

  • Supportive care

  • Azacitidine

  • Intensive chemotherapy - consider if good PS, minimal co-morbidities, no high risk karytopic abnormalities



Median age 76 years old.

Median survival only 20 months.

Molecular – Poor prognosis with SRSF2 or ASXL1 mutation. TET2 mutation no prognostic signif.

Cytogenetics usually normal

Non-transplant Mx = supportive care +/- hydroxycarbamide. Azacitidine for CMML-2


Other Poor Prognosis Cytogenetic Subtypes

SRSF2 mutation in MDS with Ring Sideroblasts

TP52 mutation adds poor prognosis in all MDS subtypes.