Haem: Myelodysplastic syndromes and Aplastic anaemia Flashcards
Define myelodysplastic syndrome.
Biologically heterogenous group of acquired haematological stem cell disorders.
What is the defining pathophysiological characteristics of myelodysplastic syndromes?
- Development of a clone of marrow stem cell with abnormal maturation resulting in functionally defective blood cells and a reduction in cell counts
- This leads to 3 main features:
* cytopaenia
* functional abnormalities of cell maturation
* increased risk of transformation to leukaemia
Typicaly age range does Myelodysplastic syndromes affect
Elderly (>60)
How do myelodysplastic syndromes typically present?
Bone marrow failure (cytopenias) developing over weeks/months
List and describe some blood film and bone marrow features of myelodysplastic syndromes.
- Pseudo-Pelger-Huet anomaly (bilobed neutrophils with decreased granules)
- Dysgranulopoeisis of neutrophils (decreased granules)
- Dyserythropoiesis of red blood cells (lack of separation between red cell precursors - cytoplasmic bridges, presence of abnormal ring of cytoplasm around the nucleus of percursor red cells)
- Increased ring sideroblasts
- Dysplastic megakaryocytes (micro-megakaryocytes)
- Increased proportion of blast cells in the bone marrow BUT NOT over 20% (normally < 5%)
Differentiate between AML and Myelodysplastic Syndrome
BY DEFINITION:
Myelodysplastic < 20% blast cells in bone marrow
Myeloid > 20% blast cells in bone marrow
What does this image show?
Pelger-Huet anomaly
What does this image show?
Dysgranulopoiesis (failure of neutrophil granulation)
What does this image show?
Lack of separation between red cell precursors, presence of abnormal ring of cytoplasm around the nucleus of precursor red cells)
What does this image show?
Ringed sideroblast (accumulation of iron around the nuclei of red blood cell precursors)
What is the presence of myeloblasts with Auer rods suggestive of?
Acute myeloid leukaemia - it is pathognomonic
Diagnostic Criteira for Myelodysplastic Syndrome
- Cytopenia of at least 1 blood cell line
- < 20% blasts in blood and bone marrow
- Either
- characteristic cytogenic or molecular finding
- morphological dysplasia >10% of nucleated cells
What are the four prognostic variables that are used to calculate prognostic risk using the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes?
Cytogenetics
Molecular Data
Age
Clinical data (BM blast%, cytopaenia, karyotype)
How does myelodysplasia tend to evolve from the time of diagnosis?
Blood counts will decrease (leading to worsening bone marrow failure) - *strong correlation between severity of cytopenia + overall life expectancy *
Then many develop acute myeloid leukaemia (poor prognosis)
Death causes: infection (commonest), bleeding, leukaemia
What are the two treatments that can prolong life in myelodysplastic syndromes?
- Allogeneic stem cell transplantation
- Intensive chemotherapy
NOTE: as most MDS patients are elderly, they often cannot tolerate treatment
List some other treatments that may be used in myelodysplastic syndromes.
- Supportive Care (blood products, antimicrobials, growth factors (e.g. EPO, GM-CSF)
- Biological modifiers
- Immunosuppression
- Azacytidine (hypomethylating agent)
- Decitabine
- Lenalidomide (used in 5q minus syndrome)
- Oral chemotherapy (e.g. hydroxyurea)
- Low-dose chemotherapy (SC low-dose cytarabine)
Define Aplastic Anaemia
Inability of BM to produce adequate blood cells - damage or suppresion of stem cell or committed progenitor cell.
Note = aplastic anaemia refers to anaemia but may also include failure to produce all types of blood cells.
List some causes of primary bone marrow failure.
CONGENITAL
* Fanconi anaemia (multipotent stem cell)
* Diamond-Blackfan syndrome (red cell progenitor)
* Kostmann syndrome (neutrophil progenitor)
ACQUIRED:
* idiopathic aplastic anaemia (multipotent stem cell)
List some secondary causes of bone marrow failure.
Marrow infiltration
* Haematological malignancies (e.g. leukaemia, lymphoma, myelofibrosis)
* Non-haemaetological (e.g. solid tumours, mets)
Aplastic
* Infection (e.g. Parvovirus B19, TB, HIV)
* Radiation
* Drugs
* Chemicals (e.g. benzene)
* Autoimmune (e.g. SLE)
List some drugs that can cause bone marrow failure.
- Cytotoxic drugs (predicatble, dose-dependent)
- Antibiotics - chloramphenicol, sulphonamides
- Diuretics - thiazide
- Antithyroid drugs - carbimazole
Which age groups are affected by aplastic anaemia?
Bimodal distribution: 10-24 and 60+
NOTE: this is much more rare than MDS
What is the most common cause of aplastic anaemia?
Idiopathic (70-80%)
List some inherited causes of aplastic anaemia.
- Fanconi anaemia
- Schwachman-Diamond syndrome
- Dyskeratosis Congenita
Outline the possible pathophysiology of idiopathic aplastic anaemia.
- Characterised by failure of the bone marrow to produce blood cells
- Either due to an inherent issue with the stem cells (CD34, LTC-IC) and/or due to autoimmune attack on stem cells
- Also features short telomeres
