W26 - myelodysplastic syndrome Flashcards
What are myelodysplastic syndromes (MDS)
Biologically heterogeneous group of acquired haemopoietic stem cell disorders, characterised by the development of a clone of marrow SCs with abnormal maturation
What are the 3 end results of myelodysplstic syndromes?
functionlly defective blood cells and numerical reduction leads to:
- cytopaenia(s)
- Functional abnormalities of erythroid, myeloid, and megakaryocyte maturation
- Increased risk of transformation to leukaemia
Myelodysplastic synromes - do they typically affect young/elderly?
Elderly
Symptoms of myelodysplastic syndromes
similar to BM failure
- low red cells (fatigue, SOB, anaemia, pallor)
- low WCC (recurrent infections)
- low platelets (recurrent bleeds)
5 blood and BM features of MDS
- Pelger-Huet anomaly (bilobed neutrophils)
- Dysgranulopoieses of neutrophils
- Dyserythropoiesis of red cells
- Dysplastic megakaryocytes – e.g. (micro-megakaryocytes in BM)
- Increased proportion of blast cells in marrow (normal < 5%)
What does peripheral blood here show?

Pelger-Huet anomaly (bilobed neutrophil) => MDS
What does this BM slide show?

desgranulopoiesis (only 4-5 granules, should be much more) => MDS
What do these 2 show?

left = red cell precursors joined by cytoplastic bridge
right = red cell precusor where cytoplsm is blebbing
= dyserythropoiesis => MDS
What does this BM slide show?

Ringed sideroblasts - iron loaded mitochondria stained with Prussian Blue => MDS
Peripheral smear - what do you see?

2 blast cells with auer rods (rod-like structure) = ACUTE MYELOID LEUKAEMIA (AML)
How is MDS prognosis determined? Name the 5 criteria
using the IPSS - International Prognostic Scoring System
- BM blast %
- Karyotype
- Hb (g/L)
- Platelet count
- Neutrophil count
Name 1 driver mutation in MDS? what is the importance of identifying these?
TP53
carry prognostic significance
Rule of thumb for outcome of MDS
1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia
Treatments (4) for MDS
- Supportive (blood products, abx, growth factors like epo for RBC, GCSF for neutrophil)
- Biological modifiers (immunosuppressive therapy)
- Allogeneic SCT (if young + matched donor)
- Intestive chemotherapy (if residual healthy stem cell)
- or low dose if intensive is unsuitable
Which one of the following is true?
- Myelodysplasia has a bi-modal age distribution
- The primary modality of treatment of MDS is by intensive chemotherapy
- One third of MDS patients can be expected to die from leukaemic transformation
- There is no good correlation between the severity of the cytopenias and the overall life expectancy
- White cell function is frequently well preserved in MDS
3.One third of MDS patients can be expected to die from leukaemic transformation
describe the right and left BM

left = normal BM (50% is fat, the other pink stuff are cells, bigger cells are megakaryocytes)
right = aplastic BM (hypocellular)
Aplastic anaemia
- incidence
- peak incidence (age)
Aplastic anaemia
- incidence:
2-5 cases/million/yr
- peak incidence (age):
2 peaks: 15-24 yrs, >60 yrs
4 classifications of aplastic anaemia
1. Idiopathic (most common, 70-80%)
2. Inherited (Dyskeratosis congenita, Fanconi anaemia, etc)
3. Secondary:
- Radiation
- Drugs (i.e. cytotoxic drugs, chlorampheniocol)
- Viruses (i.e. hepatitis)
- Immune (i.e. SLE)
4. Miscellaneous (i.e. Paroxysmal nocturnal haemoglobinuria, thymoma)
Idiopathic aplastic anaemia pathophysiology
Failure of BM to produce blood cells
Thought to be an immune attack = B or T cell attack against multipotent HSCs
Clinical presentation (3) of aplastic anaemia
- Anaemia = Fatigue, breathlessness
- Leucopenia = Infections
- Platelets = Easy bruising/bleeding
How is aplastic anaemia diagnosed?
- Blood shows cytopaenias
- BM showed hypocellularity
What is the criteria used for diagnosing the severity of aplastic anaemia?
Name the criteria
Camitta criteria:
2 out of 3 peripheral blood features:
- Reticulocyte
- Neutrophils
- Platelets
+ BM <25% cellularity
Management (6) of aplastic anaemia (BM Failure)
- Remove cause, if possible (i.e. radiation)
- Supportive (blood products, abx, iron chelation therapy if iron overloaded from RBC transfusion)
- Immunosuppressive therapy
- Drugs to promote marrow recovery
- SCT (if young + matched donor)
- Other tx for refractory cases (biologic therapies)
Aplastic anaemia - who would benefit from a SCT?
Younger patient with donor (80% cure)
% falls if match isn’t a sibling donor and patient age >40 y.o.

