Myelodysplasia Flashcards
[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
<20%;
AML (blasts >20%);
alkylating agents or radiotherapy
[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)
increase in % blasts;
proliferate indefinitely;
constant transfusion;
leukaemia
What are the clinical features for MDS?
Anaemia: Fatigue, breathlessness
Thrombocytopenia:
- Bruising with minimal trauma or blood blisters in the mouth
- Physical findings include ecchymosis, bleeding gums and epistaxis.
Neutropenia: Infections
What are the investigations performed for MDS?
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
What is the prognosis of MDS?
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
What is the management of MDS?
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