Haematology 13 - Myelodysplastic syndromes and aplastic anaemias Flashcards
Definition of MDS
How is MDS different to MPN and leukamiea?
What is the difference between MDS and aplastic anaemia?
Basically: qualitative and quantitative defect of cells of different part sof the myeloid lineage
“Heterogeneous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells.”
MDS vs MPN and leukaemia
MDS: defective prolfieration and defective differentiation
MPN: increased proliferation, intact differentiation
Leukamiea: increased proliferation, some defective differentiation
**can be a degree of overlap
MDS vs aplastic anaemia
MDS- bone marrow is producing cells, but the cells are abnormal
Aplastic anamiea - the bone marrow is so damaged that it’s not producing cells (hypocellular bone marrow)
Which age group usually gets MDS?
Elderly
Clinical features of MDS
1) anaemia- tired, pallor, SoB
2) leukopenia- infection
3) thrombocytopenia- bleeding, bruising
This develops over weeks and months
What are the abnormalities seen on bone marrow and blood film in MDS?
1) abnormal blast cells
2) abnormal myeloid lineage- hypogranulation, pseudo-pelger-huet anomaly (hyposegmented neutrophil)
3) abnormal RBCs- ring sideroblasts
4) abnormal platelets- micromegakaryocytes, hypolobated nuclei
**you would see a HYPERCELLULAR BONE MARROW**- contrast with aplastic anaemia where you see a hypocellular bone marrow
What abornalities of blast cells do you see in MDS?
Increased proportion of blast cells (normal <5%)
**however they must be <20% otherwise it is classed as an acute leukaemia
What abnormalities of myeloid lineage do you see in MDS?
1) myeloblasts - aeur rods (aeur rods= either AML or late stage MDS that has progressed to AML i.e. bad news)
2) abnromal neutrophils
- Pelger Huet anomaly (bilobed nucleus, with lobes separated by thin bridge)
- dysgranulopoiesis - can’t release granules
- myelokathexis (fragmentation of neutrophil nucleus)
What abnormalities of RBC do you see in MDS?
- dyserythropoiesis of RBC - erythroblasts connected by cytoplasmic bridge not broken off, blebbing of RBC
- ringed sideroblasts- deposits of iron around the RBC nucleus
Abnornalities of platelets in MDS
Usually megakaryocytes (biggest cells in the bone marrow) make the smallest cells (platelets). In MDS you get small megakaryocytes (micromegakaryocytes)
What predicts transofmration of MDS into AML?
>5% blasts in bone marrow - increased risk
more blasts- more risk of AML
What are the possible causes of death in myelodysplastic syndromes?
1/3 die of bleeding
1/3 die of infection
1/3 die of AML
What are the 2 possible curative treatments for myelodysplastic syndromes, and what is the biggest issue with them?
- Allogenic stem cell transplant
- Intensive chemotherapy
Sadly, most patients can’t benefit from either for one reason or another
In myelodysplastic syndrome patients who are not suitable for curative treatment, how should disease be managed?
Supportive treatments include:
- Blood products
- Antibiotics
- GF - EPO, GCSF (neutrophil count)
Can add biological modifiers:
- Immunosuppressive therapy
- Azacytidine
How does azacytidine work in the treatment of myelodysplastic syndromes?
Hypomethylating agent
Causes blood count to rise
What chemotherapy can be used for MDS?
Primary causes of bone marrow failure: pancytopaenia and single cytopaenia
Schwanmann Diamond- primarily neutrophilia but can affect other lineages also.
(diff to diamond-blackfann which is single red-cell aplasia)
Secondary causes of bone marrow failure
Causes of aplastic anaemia
1) idiopathic- most common. tends to be autoimmune.
2) inherited
a) fanconi’s anaemia
b) dyskeratosis congenita
c) schwachman diamond syndrome
3) secondary
a) radiation
b) drugs
c) viruses
d) immune
Recall 3 drugs that can cause bone marrow failure
- Cytotoxic drugs (eg chemo) (predictable- dose dependent)
- Antibiotics (particularly chloramphenicol) (idiosyncratic- not dose dependent. rare)
- Thiazide diuretics
Epidemiology of aplastic anaemia
- 2-5 million cases per year worldwide (RARE)
- ALL age groups can be affected
- Bimodal incidence:
- 15-24 years
- 60+ years
Clinical features of aplastic anaemia
- Anaemia- fatigue, pallor, breathlessness:
- Cannot make haemoglobin so get anaemic
- Leukopenia- infections:
- Cannot make WBCs to fight off infections
- Thrombocytopaenia- easy bruising/ bleeding/ petechial rash:
- Cannot make enough platelets
Diagnosis of aplastic anaemia
- Bloods
cytopaenia
low RBC
low Hb
low reticulocytes
high MCV - as HbF increases to compensate for low Hb
- definitive diagnosis- bone marrow biopsy
- hypocellular bone marrow filled with fat
- dry tap- low haematopoietic stem cells
Differential diagnoses of aplastic anaemia
- Hypoplastic MDS/ AML
- Hypocellular ALL
- Hairy Cell Leukaemia
- Idiopathic Thrombocytopaenic Purpura (ITP)
- Mycobacterial (usually atypical) infection
- Anorexia Nervosa:
- necrosis of bone marrow into fat if they really starve themselves)
What are the 2 classifications of aplastic anaemia, and how is classification decided?
Severe or non-severe
Decided by *Camitta criteria*:
- Aplastic anaemia is severe if 2 or more of the following peripheral blood features are present:
- Reticulocytes <1%
- Neutrophils <0.5
- Platelets <20
PLUS: Bone marrow cellularity must be <25%
Treatment of aplastic anaemia: detailed algorithm
How should idiopathic aplastic anaemia be treated? summary
For all patients: androgens (oxymethalone)
For older patients: immunosuppression (presumably because there’s immune mediated destruction)
- anti-lymphocyte globulin
- ciclosporin
For younger patients: stem cell transplant
Success rates of bone marrow transplant for aplastic anaemia
Recall some symtoms of Fanconi’s anaemia
Short stature, hypogonadism, thumb abnormality, cafe au lait spots
What is the genetic basis of dyskeratosis congenita and aplastic anaemia?
Telomere shortening
What is the triad of clinical features of dyskeratosis congenita?
- Skin pigmentation
- Nail dystrophy
- Oral leukoplakia
“SNOB” = the above triad + BM failure - useful mnemonic
What is the pseudo-pelger-huet anomaly?
Hyposegmented neutrophils seen in myelodysplastic syndromes
What is diamond blackfann anaemia?
- pure red blood cell aplasia
- other cells not affected
- craniofacial abnormalities - cleft palate, cardiac defects
- blood test
- anaemia
- low reticulocyte count
- elevated foetal haemoglobin
CHaracteristics of fanconi anaemia
main thing- pancytopaenia
What is schwachman-diamond syndrome?
Autosomal recessive. Primarily NEUTROPAENIA +/- others
• Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment,
short stature • AML risk
**think of girl you saw at clinic** - also skin problems (hypersensitivity, eczema etc. ) and learning disability
Dyskeratosis congenita
X-linked. Chromosome instability (telomere shortening)
• Skin pigmentation, nail dystrophy, oral leukoplakia (triad) + BM failure
Diamond blackfann syndrome
Pure red-cell aplasia; normal WCC and platelets
• Presents at 1yr/neonatal
• Dysmorphology (d for diamond, d for dysmorphic)
**diamond- precious; RBC- main cell**
