Myelodysplasia

Question 1

[MYELODYSPLASIA (MDS)]

• Group of acquired haematopoietic stem cell disorders (~ 4 per 100,000 persons) and typically a disorder of the elderly.
• Cells are proliferating actively but not effectively.
• The cells would have an abnormal morphology.
• Increased number of blasts but ________
• There is a tendency to develop into _________.
• Associated with prior exposure to _________________.
• Normal BM has <5% blasts

Answer 1

<20%;

AML (blasts >20%);

alkylating agents or radiotherapy

Question 2

[Pathophysiology of MDS]

Haematopoietic stem cells keep on producing abnormal ineffective blast cells

Most of these blast cells are unable to mature properly due to gene mutation, leading to ______________

However, they lack the oncogenic mutation that allows them to ________________.

Even when some of these blast cells DO develop into mature blood cells, they are defective + die off quicker
There is thus ↓ in myeloid cells 🡪 cytopenia 🡪 require _______________

Cytopenia can involve 1 or multiple cell lineages. Pt with MDS therefore present very similarly to patient with Leukaemia.

In summary
- There is an abnormal maturation of blood cells which results in
Cytopenias
- Even in matured cells, there are functional defects causing early death
- Increased Blasts (<20%)
- Increased risk of transformation to ___________ (usually considered a premalignant condition)

Answer 2

increase in % blasts;

proliferate indefinitely;

constant transfusion;

leukaemia

Question 3

What are the clinical features for MDS?

Answer 3

Anaemia: Fatigue, breathlessness

Thrombocytopenia:

• Bruising with minimal trauma or blood blisters in the mouth
• Physical findings include ecchymosis, bleeding gums and epistaxis.

Neutropenia: Infections

Question 4

What are the investigations performed for MDS?

Answer 4

If Refractory anaemia with excess of blasts-1 and 2
- Increased proportion of blast cells in marrow (normal < 5%)

Possible dysplasia we may see in PBF/BM include:

Neutrophils

• Pelger-Huet anomaly (bilobed neutrophils connected by thin strand)
• Hypersegmented Neutrophils (also seen in vit B12/folate deficiency)
• Hyposegmented Neutrophils (pseudo pelger-huet)
• Auer Rods (seen in AML as well as REAB-2)
• Dysgranulopoieses of neutrophils (absence / abnormal granules)

RBC

• Binucleated erythroid precursors
• Dyserythropoiesis of red cells (abnormal morphological forms - cytoplasmic/nuclear bridging, etc.)
• Ringer Sideroblasts (Refractory anaemia with ring sideroblasts (RARS)

Megakaryocytes
- Dysplastic megakaryocytes e.g. micro-megakaryocytes

Question 5

What is the prognosis of MDS?

Answer 5

Development of acute myeloid leukaemia

• Develops in 50%< 1 year
• Some cases of MDS are much slower to evolve
• AML from preceding MDS extremely poor prognosis; usually not curable

As a rule of thumb

• 1/3 die from infection
• 1/3 die from bleeding
• 1/3 die from acute leukaemia

Question 6

What is the management of MDS?

Answer 6

At present, the only 2 treatments that can prolong survival:

• Allogeneic stem cell transplantation (SCT): Usually done for pt <50YO with a HLA matched sibling
• Intensive chemotherapy but only a minority of MDS patients can really benefit from them

Supportive:

• Blood product support, antimicrobial therapy, growth factors (EPO, G-CSF)
• Biological modifiers: Immunosuppresive therapy/ Azacytidine/ Lenalidomide