Myelodysplastic syndromes Flashcards
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
what is the pathophysiology of fanconi anaemia ?
Multiple mutated genes are responsible.
what is the Treatment Algorithm for Severe Aplastic Anaemia?
A. <35 and sibling with matchign HLA:
- HLA matched stem cell transplant (HSCT)
if not. and has kids -> unrelated SCT
B. >50:
Ciclosporin (immunosuppresant) + ATG
Relapse -> unrelated SCT or. repeat above
C. 35-50 :
can try either regimen
