Myelodysplasia Flashcards
Define myelodysplasia/ myelodysplastic syndromes.
Acquired haemopoietic stem cell disorders
Characterised by development of a clone of marrow stem cells with abnormal maturation resulting in functionally defective blood cells AND a numerical reduction
i.e. abnormal myeloid clone forms + number is reduced
What is the prognosis with myelodysplasia?
Can transform into AML (about 30% of the time)
What is the aetiology of myelodysplastic syndromes?
Primary or secondary to chemo/radiotherapy.
May show chromosomal abnormalities:
- deletions e.g. partial/total loss of chromosomes 5,7, 20 or Y
- monosomy 7
- trisomy 8
- complex karyotypes with multiple abnormalities
What are the risk factors for myelodysplasia?
- Age >70yrs
- Alkylating agents
- Topoisomerase inhibitors
- Prior haematopoietic stem cell transplantation
- DNA repair deficiency syndrome
- ionising radiation
- tobacoo
- benzene
- aplastic anaemia
- paroxysmal nocturnal haemoglobinuria (PNH)
- Down’s syndrome (trisomy 21)
- congenital neutropenia
Who is usually affected by myelodysplasia?
- 65-75yr old men
- Twice as common as AML
What are the signs and symptoms of myelodysplasia?
Asymptomatic and diagnosed after routine bloods in 50%
Symptoms of BM failure:
- Anaemia - fatigue, dizzy
- Neutropaenia - infections
- Thrombocytopenia - easy bruising, epistaxis
Signs of BM failure:
- Anaemia - pallor, cardiac flow murmur
- Neutropaenia - infections
- Thrombocytopaenia - purpura or ecchymoses
- Gum hypertrophy
- Lymphadenopathy
- Spleen NOT ENLARGED - except in CMML
What is the prognosis?
Most die of infection in myelodysplasia stage of disease
Some progress rapidly to AML
NB: difference between MDS and AML: MDS is diagnosed when blasts in BM are <20%, AML is when blasts are >20%.
How is the diagnosis of myelodysplasia made?
Diagnosis of MDS is made when BM shows
- Significant dysplasia
- Clonal cytogenetic abnormality
- Quantitative changes in at least one of the blood cell lines
- Blasts <20%
What investigations would you do for myelodysplasia?
Work up mainly includes:
- FBC -everything LOW
- peripheral smear
- bone marrow aspiration with iron stain - single or multilineage dysplasia; bone marrow blasts <20%
- core biopsy with cytogenetic analysis - hypercellular marrow with chromosomal abnormalities. Ringed sideroblasts, abnormal granulocyte precursors and megakaryocytes. 10 % show fibrosis.
What are the causes of death in MDS?
As a rule of thumb
- 1/3 die from infection
- 1/3 die from bleeding
- 1/3 die from acute leukaemia
What treatments for MDS prolong survival?
- Allogeneic stem cell transplantation
- Intensive chemotherapy - most are not good candidates for this due to age
What supportive therapy can be given in MDS?
- Blood products
- Abx
- Growth factors (EPO, G-CSF, TPO)
What biologics are used in MDS?
- Immunosuppressant
- Hypomethylating agents - azacytidine, decitabine
- Lenalidomide for del5q variant
What chemotherapies are used in MDS?
Hydroxyurea
Cytarabine
What is seen on blood film in MDS?
Bilobed neutrophils (Pelger-Huet abnormality)
Myelokathexis - increased number of mature hypersegmented neutrophils
Ringed sideroblasts - haemosiderin deposits in the mitochondria of erythroid precursors form an apparent ring around the nucleus
Myeloblasts with Auer rods
