Haematology 7: Myelodysplastic Syndrome Flashcards
What are the haematological features of Myelodysplastic syndrome ?
Cytopaenias
Qualitative abnormalities of erythrocytes, myelocytes and megakaryocytes maturation
increased risk of transformation into leukaemia
Name the characteristic bilobed neutrophil seen in MDS ?
Pseudo Pelger-huet anomaly
List some abnormal cells seen with microscopy in MDS ?
Pseudo Pelger huet neutrophils (bilobed)
Dysgranulosis of neutrophils
Dyserythropoiesis of red cells
Ringed sideroblasts - iron granules visible
Micro megakaryocytes ( dysplastic megakaryocytes)
Increased proportion of blast cells in marrow
Myeloblasts with auer rods (also feature of AML)
Which disease does MDS often progress to ?
AML
Which drug can be used to treat MDS 5q- syndrome ?
Lenalidomide
List 3 Primary causes of bone marrow failure ?
Fanconi’s anaemia
Diamond blackfan anaemia
Kostmann’s syndrome
Acquired: idiopathic aplastic anaemia
Which 2 antibiotics can cause bone marrow failure ?
Chloramphenicol
Sulphonamide
How is fanconi anaemia inherited ?
Mainly autosomal recessive but some are X linked
List 4 congenital abnormalities seen in children with Fanconi anaemia ?
Absent radii
Abnormal thumbs
Cafe au lait spots
Short stature
What is the pathognomonic triad of clinical signs of Dyskeratosis Congenital (DC)?
Skin pigmentation
Nail dystrophy
Leukoplakia
These children look very old! The disease causes premature aging
What is the genetic cause of Dyskeratosis congenita ?
Mutation in Genes that encode proteins involved in maintenance of telomerases. These telomerases get shortened at the ends. This causes premature ageing
define myelodysplastic syndrome
biologically heterogeneous group of acquired haematopoietic stem cell disorders
characterised by development of a clone of marrow stem cells with abnormal maturation resulting in:
- functionally defective blood cells
- numerical reduction
usually elderly
develops over weeks/months
prognosis of patients with MDS
1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia
treatment options for MDS
allogenic stem cell transplant
intensive chemotherapy
supportive - blood products, antimicrobial, growth factors
biological modifiers - immunosuppressive agents, azacytidine, decitabine, lanalidomide
oral chemotherapy - hydroxyurea/hydroxycarbamide
low dose chemo - subcutaneous low-dose cytarabine
intensive chemo/stem cell transplant - for high risk MDS - AML-type regimes
secondary causes of bone marrow failure
marrow infiltration haematological malignancies (leukaemias, lymphomas) non-haematological (solid tumours) radiation drugs chemicals (eg benzene) AI infection (parovirus, viral hepatitis)
what drugs can cause bone marrow failure
predictable - cytotoxic drugs
idiosyncratic - phenylbutazone, gold salts
antibiotics - chloramphenicol, sulphonamide
diuretics - thiazides
antithyroid drugs - carbimazole
what is aplastic anaemia
deficiency of RBC, WBC, and platelets
all age groups affected
bimodal incidence - 15-24, 60+
what are the different types of aplastic anaemia
most = idiopathic inherited = dyskeratosis congenita, fanconi anaemia, schwachman- diamond syndrome secondary = radiation, drugs, hepatitis viruses, SLE
describe the clinical presentation of bone marrow failure
anaemia - fatigue, breathlessmess
leucopaenia - infections
thrombocytopeania - bleeding/ bruising
how is aplastic anameia diagnosed
peripheral blood - cytopeania
bone marrow - hypocellular
what are the two subtypes of aplastic anaemia
severe aplastic anaemia (SAA)
non-severe aplastic anaemia (NSAA)
what is the camitta criteria for severe aplastic anaemia
2/3 peripheral blood features
- reticulocytes <1% (<20 x 109/l)
- neutrophils <0.5 x 109/l
- platelets <20 x 109/l
how is bone marrow failure managed
seek and remove cause supportive - blood transfusion/ platelet transfusion iron chelation therapy immunosuppressive therapy SC transplant (younger patients)
describe features of fanconi anaemia
most common AA autosomal recessive/ x linked multiple mutated genes involved gene mutations result in: - abnormalities in DNA repair - chromosomal fragility - breakage in the presence of in vitro mitomycin/ diepoxybutane
what are clinical features of fanconi anaemia
short stature hypopigmented spots and cafe au lait spots abnormality of thumbs microcephaly or hydrocephaly hypogonadism developmental delay no abnormalities in 30%
list complications of fanconi anaemia
aplastic anaemia leukaemia liver disease myelodysplasoa cancer (epithelial)
what is dyskaryosis congenita
inherited disorder characterised by:
- marrow failure
- cancer predisposition
- somatic abnormalities
how do patients with dyskaryosis congenita present
skin pigmentation
nail dystrophy
leukoplakia
list somatic abnormalities/complications in DC
abnormal skin pigmentation
nail dystrophy
BM failure
leukoplakia
what is the genetic basis of dyskaryosis congenita
telomere shortening
3 patterns of inhetritance:
- X-linked recessive (most common) - mutant DKC1 gene leads to ineffective telomere functioning
- Autosomal dominant - mutant TREC gene - encodes RNA component of telomerase
- Autosomal recessive - ? mutant gene
what is the function of telomeres
prevent chromosomal fusion or rearrangements during chromosomal replication
protects genes at end of chromosomes from degrading
telomere length reduced in BM failure diseases
how is severe aplastic anaemia treated
age <35:
- HLA identical sibling donor/child or unrelated donor
age 35-50:
- HLA donor or horse anti-thymocyte gobulin (ATG_ + ciclosporin) - unrelated HCA donor/ eltrombopag + 2nd ATG
