Myelodysplastic syndromes Flashcards
(26 cards)
what is MDS/ myelodysplasia?
If it helps; a previous name was ‘pre-leukaemia’.
The symptoms are in line with this; they get your symptoms of cytopaenia (anaemia and co, easy bruising, increased infections) but not the symptoms of organ mets/infiltration (hepatic/splenomegaly etc) becuase it is not cancer, rather a bone marrow ‘failure’ (failure of maturation).
mean age is 65
list some Blood & Bone Marrow Morphological Features of MDS
The 3 cell lines affected:
- Dysgranulopoieses of neutrophils - means they dont form properly so can have a range of defects from no granules to macrocytosis to:
Pelger-Huet anomaly (bilobed neutrophils) - Dyserythropoiesis of red cells
- basophilic stippling of rbcs - Dysplastic megakaryocytes – e.g. micromegakaryocytes
Increased proportion of blast cells in marrow (normal < 5%)
ringed sideroblasts
large agranular platelets
the presence of which cells are pathognomic in MDS?
what are they?
Blast cells in bone marrow and peripheral blood
Ringed sideroblasts: when BM aspirate is taken and stained, erythroid precursor cells who’s nuclei are surrounded by blue granules - haemosiderin deposits
which stain is required to see Ringed sideroblasts?
haemosiderin stain
The 2016 WHO classifcation of MDS subtypes includes which categories?
No. of dysplastic lineages/cell types (1-3)
No. of cytopaenias (1-3)
Ringed sideroblasts as % of marrow
BM and peripheral blood blasts %
Cytogenetics!! eg 5q- deletions and more
what does a high Prognostic Score mean in MDS?
The higher the score, the lower the survival and time to progress to AML
what kills in MDS?
- 1/3 die from infection
- 1/3 die from bleeding
- 1/3 die from acute leukaemia
what are the subtypes of MDS?
MDS with single lineage dysplasia (old term refractory anaemia - low RBCs)
MDS with multilineage dysplasia (OT refractory cytopenia)
MDS with excess blasts (OT refractory anaemia with excess blasts) -> has 5-9% + BM blasts and similar peripheral blasts. other forms have <5% blasts.
How is MDS treated?
Supportive care:
EPO &/ G-CSF - replace cytopaenia
Blood transfusion
Abx
Lenalidomide pill - used to treat a rare type of MDS called deletion 5q
Azacitidine - hypomethylating agent - more serious MDS
Chemotherapy (oral or iv) followed by Autologous SCT - more serious MDS, with risk of AML not primary treatment.
what are the causea on BM failure?
Primary:
genetic and congenital
Secondary Marrow infiltration: Haematological ( leukaemia, lymphoma, myelofibrosis) Non-haematological (Solid tumours, ) Radiation Drugs Chemicals (benzene) Autoimmune Infection (Parvovirus, Viral hepatitis
which drugs can cause BM failure?
PREDICTABLE (dose-dependent, common)
Cytotoxic drugs
IDIOSYNCRATIC (NOT dose-dependent, rare)
Phenylbutazone
Gold salts
ANTIBIOTICS
Chloramphenicol
Sulphonamide
DIURETICS
Thiazides
ANTITHYROID DRUGS
Carbimazole
WHAT IS THE EPIDEMIOLOGY OF APLASTIC ANAEMIA?
Bimodal distribution:
15 to 24 yrs
60 yrs
what is the aetiology of aplastic anaemia?
80% = Idiopathic
Failure of BM to produce blood cells
• “Stem cell” problem (CD34, LTC-IC) [Long-Term Culture-Initiating Cells]
• Immune attack:
Humoral or cellular (T cell) attack against multipotent haematopoietic stem cell.
how. does. aplastic anaemia present?
Triad:
- Anaemia Fatigue, breathlessness
- Leucopenia Infections
- Platelets Easy bruising/bleeding
how is severe and non-severe aplastic anaemia diagnosed?
Non-severe:
- Blood Cytopenia
- Marrow Hypocellular
note: other conditions eg AML can present like this
Severe:
2 out of 3 peripheral blood features
- Reticulocytes < 1% (<20 x 109/l)
- Neutrophils < 0.5 x 109/l
- Platelets < 20 x 109/l
Bone marrow <25% cellularity
how is APLASTIC ANAEMIA treated?
- Supportive:
blood, abx, iron chelation - Specific:
A. Immunosuppressive therapy – older patient
Anti-Lymphocyte Globulin (ALG)
Ciclosporin
B. Androgens – oxymethalone
C. Stem cell transplantation
what are the most common late COMPLICATIONS FOLLOWING IMMUNOSUPPRESSIVE THERAPY FOR AA?
- Relapse of AA (35% over 15 yrs)
- Clonal haematological disorders ~ 20% risk
Myelodysplasia
Leukaemia
PNH (paroxysmal nocturnal haemoglobinuria) - Solid tumours
what are the presenting sx in fanconi anaemia?
Short Stature Hypopigmented spots and café-au-lait spots Abnormality of thumbs Microcephaly or hydrocephaly Hyogonadism Developmental delay No abnormalities 30%
WHAT IS THE PATTERN OF INHERITANCE IN FANCONI ANAEMIA?
Autosomal recessive or X-linked inheritance
List some complications of FA?
Aplastic anaemia - 90 by 9y/o
Myelodysplasia - 32% by age 17
Leukaemia - 16% by age 14
cancer - 5% by age 23
In which condition do patients present with the Classical Triad of:
Skin pigmentation
Nail dystrophy
Leukoplakia
DYSKERATOSIS CONGENITA (DC)
what is the MANAGEMENT protocol OF BONE MARROW FAILURE?
- Supportive: Blood/platelet transfusions
Antibiotics
Iron Chelation Therapy (possibly) - Drugs to promote marrow recovery
TPO receptor agonists (e.g. eltrombopag)
?Oxymetholone?
??Growth factors?? - Stem cell transplantation
what is the pathophysiology of DYSKERATOSIS CONGENITA ?
Telomere shortening
- Telomere length is reduced marrow failure diseases but even more in DC
X-linked recessive trait — the most common inherited pattern (mutated DKC1 gene - defective telomerase function).
Autosomal dominant trait —
Autosomal recessive trait —
what is the main difference betweeen DC and Idiopathic AA?
DYSKERATOSIS CONGENITA
aplastic anaemia
no Physical abnormalities in AA as in DC
genetic associations. identified in DC
