Haem - Myelodyplasia and Aplastic anaemia Flashcards
What are myelodysplastic syndromes and what are the characterised by
Heterogeneous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells.
- Cytopenia
- Qualitative (functional) abnormalities of erythroid, myeloid and megakaryocyte maturation
- Increased risk of transformation to leukaemia (AML)
What are the clinical features of myelodysplasia
Elderly
Symptoms develop over weeks-months
BM failure and cytopenias – infection, bleeding, fatigue
What are the features of myelodysplasia in the blood
RBCs:
Dyserythropoiesis of red cells (lack of separation between RBC precursors)
Ringed sideroblasts (iron granules in red cell precursors, iron deposited in mitochondria in a ring around the nucleus)
Ferritin may be elevated– ineffective erythropoiesis
Granulocytes:
Pelger-Huet anomaly (bilobed neutrophils)
Dysgranulopoiesis of neutrophils (low granule number)
Dysplastic megakaryocytes – e.g. micro-megakaryocytes
Increased proportion of blast cells in marrow (5-20%)
What is RAEB-T
Refractory anaemia with excess blasts in
transformation
21-30% myeloblasts in the marrow – now
considered as AML.
Describe the evolution of myelodyslplasias
- Deterioration of blood count
- Worsening consequences of marrow failure - Development of acute myeloid leukaemia (AML)
- Develops in 5-50% <1 year (depends on subtype)
- Some cases of MDS are much slower to evolve
- AML from MDS has an extremely poor prognosis and is usually not curable - Death:
- 1/3 die from infection
- 1/3 die from bleeding
- 1/3 die from acute leukaemia
What is the treatment for myelodysplasia
Supportive: transfusion, antimicrobial therapy, growth factors (EPO, G-CSF, TPOr-atagonist)
Biological modifiers: immunosuppressive therapy, hypomethylating agents, lenalidomide
Treatments to prolong survival: allogenic stem cell transplant (A-SCT) OR intensive chemotherapy
What is the WHO classification of myelodysplastic syndromes
Refractory anaemia (RA): with (RARS) or without ringed sideroblasts
- anaemia, no blasts, dysplasia <5% blasts OR >15% ringed sideroblasts
Refractory cytopenia with multilineage dyspalsia (RCMD)
- cytopenia and dysplasia (>10% cells) in 2 or more cell lines
Refractory anaemia with excess of blasts (RAEB): RAEB-I (blasts 5-9%) or RAEB-II (blasts 10-19%)
5q syndrome
- anaemia, megakaryocytes with hypolobulated nuclei <5% blasts
Unclassified: with fibrosis, childhood, others
What is aplastic anaemia
Bone marrow failure from damage/suppression of stem/progenitor cells
May be committed progenitor cells (bi- or uni-cytopenia) OR pluripotent haematopoeitic cells (pancytopenia)
What are the causes of aplastic anaemia
3
What drugs can cause aplastic anaemia
Cytotoxic drugs (predictable)
Phenylbutazone, gold salts (idiosyncratic, not dose dependent)
Chloramphenicol, sulphonamides
Thiazides
Carbimazole
What is the epidemiology of aplastic anaemia
Rarer than myelodysplasia
Bimodal peaks: 15-24 and >60yo
What are the clinical features of aplastic anaemia
Anaemia – fatigue, breathlessness
Leucopaenia – infections
Thrombocytopaenia – bleeding/bruising
What is the criteria for severe aplastic anaemia
(Camitta criteria) 2 out of 3 peripheral blood features:
1. Reticulocytes < 1% (<20 x 109/L)
2. Neutrophils < 0.5 x 109 /L
3. Platelets < 20 x 109 /L
+ Bone marrow <25% cellularity
What is the management for aplastic anaemia
- Seek and remove any causes
- Supportive: transfusions, Abx, iron chelation
- Immunosuppression: anti-thymocyte globulin, steroids, Eltrombopag, cyclosporine A
- Drugs for marrow recovery (androgens (oxymetholone), thrombopoietin receptor agonists (Eltrombopag))
- Stem cell transplantation
What is the prognosis for aplastic anaemia
Stem cell transplantation tends to be used in younger patients: <40yo → 80% cure rate
25% risk of relapse
Risk of myelodysplasia, leukaemia and Paroxysmal nocturnal haemoglobinuria (PNH)
What is Fanconi anaemia
Congenital aplastic anaemia (most common form of inherited AA)
Autosomal recessive or X-linked
Multiple mutated genes → abnormal DNA repair and chromosomal fragility
What are the clinical features of Fanconi anaemia
Presents at 5-10yo
Short Stature
Hypopigmented spots and café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Hypogonadism
Developmental delay
No abnormalities 30%
What are the complications of Fanconi anaemia
32% progress to myelodysplasia
10% progress to AML
What is dyskeratosis congenita
An inherited disorder characterised by:
- Marrow failure
- Cancer predisposition
- Somatic abnormalities: leukoplakia, nail dystrophy, skin pigmentation
What is the genetic basis for dyskeratosis congenita
Due to telomere shortening
X-linked recessive (most common): DKC1 gene mutation
Autosomal dominant: TERC gene
Autosomal recessive
Describe Schwachman-Diamond Syndrome
Autosomal recessive
Primarily neutrophilia ± others
Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature
AML risk
Describe Diamond-Blackfan Syndrome
Pure red-cell aplasia; normal WCC and platelets
Presents at 1yr/neonatal
Dysmorphology
What is the treatment for severe aplastic anaemia
<35: ?HLA identical sibling → HLA matched HSCT (if not → unrelated donor HSCT
35-50: either HSCT or horse ATG
>50: horse anti-thymocyte globulin (ATG) + ciclosporin
