Myelodysplastic Syndromes and Aplastic Anaemia Flashcards
What are myelodysplastic syndromes?
Biologically heterogeneous groups of acquired haemopoietic stem cell disorders
What characterises myelodysplastic syndromes?
The development of a clone of marrow stem cells with abnormal maturation resulting in functionally defective blood cells AND numerical reduction
Is also associated with increased risk of transformation to leukaemia
What are the presenting features of myelodysplasia?
Typically a disorder of the elderly
Symptoms/signs are those of general marrow failure
Develops over weeks & months
What are the morphological features of blood and bone marrow in myelodysplastic syndrome?
Pelger-Huet anombaly (bilobed neutrophils)
Dysganulopoiesis of neutrophils
Dyserythropoiesis of red cells
Dysplastic megakaryocytes e.g. micro-megakaryocytes
Increased proportion of blast cells in marrow
What is the normal proportion of blast cells in bone marrow?
<5%
What is the classification of MDS based on?
Number of dysplastic lineages Percentage of blasts in bone marrow and peripheral blood Cytogenetic findings Percentage of ringed sideroblasts Number of cytopenias
What is an important gene mutation in MDS?
TP53
EZH2, ETV6, RUNX1, ASXL1
What increases the chance of MDS developing into acute myeloid leukaemia?
High blast cells
What is the rule of 1/3rds in MDS?
1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia
Why is AML that has progressed from MDS hard to treat?
No functioning stem cell
What are the treatment options for MDS?
Allogenic stem cell transplantation (SCT)
Intensive chemotherapy
However, as majority of patients are elderly they are unlikely to tolerate these
What supportive care is given to patients with MDS?
Blood product support
Antimicrobial therapy
Growth factors (Epo, G-CSF), TPO-Receptor Agnoist)
What biological modifiers can be used in treatment of MDS?
Immunosuppressive therapy
Hypomethylating agents
Lenalidomide (for del(5q) variant)
What chemotherapies can be used in MDS?
Oral: hydroxyurea
Low dose sub cut cytarabine
What is bone marrow failure?
Results from damage or suppression of stem or progenitor cell
What are the types of bone marrow failure?
Pluripotent haematopoietic cell - impairs production of all peripheral blood cells - RARE
Committed progenitor cells - results in bi-or unicytopenias
What are the primary causes of bone marrow failure?
Congenital: Fanconi’s anaemia (multipotent stem cell)
Diamond-Blackfan anaemia (red cell progenitors)
Kostmann’s syndrome (neutrophil progenitors)
Acquired: idiopathic aplastic anaemia (multipotent stem cell)
What are the secondary causes of bone marrow failure?
Marrow infiltration Haematological (leukaemia, lymphoma, myelofibrosis) Non-haematological (solid tumours) Radiation Drugs Chemicals (benzene) Autoimmune Infection (Parvovirus, viral hepatitis)
How can we break down the types of drugs that cause marrow failure?
Predictable e.g. cytotoxic Isiosyncratic - rare Antibiotics Diuretics Antithyroid drugs
What antibiotics can cause marrow failure?
Chloramphenicol
Sulphonamide
What diuretics can cause marrow failure?
Thiazides
What antithyroid drug can cause marrow failure?
Carbimazole
What is the epidemiology of aplastic anaemia?
2-5cases/million/yr
All age groups can be affected
Peak incidence: 15-24yrs and >60yrs
What is the classification of aplastic anaemias?
Idiopathic - vast majority
Inherited
Secondary
Miscellaneous
Give examples of inherited aplastic anaemia
Dyskeratosis congenita (DC) Fanconi anaemia (FA) Shwachman-Diamond syndrome
What are some secondary causes of aplastic anaemia?
Radiation
Drugs e.g. cytotoxic agents, chloramphenicol, NSAIDs
Viruses e.g. hepatitis
Immune: SLE
What are the miscellaneous causes of aplastic anaemia?
PNH (Paroxysmal nocturnal haemoglobinuria)
Thymoma
What is the pathophysiology of idiopathic AA?
Failure of BM to produce blood cells
‘Stem cell’ problem (CD35, LTC-IC) [Long-Term Culture-Initiating Cells]
Immune attack:
Humoural or cellular (T cell) attack against multipotent haematopoietic stem cell
What are the clinical findings of aplastic anaemia?
Anaemia - fatigue, breathlessness
Leucopenia - infections
Platelets - easy bruising/bleeding
How is aplastic anaemia diagnosed?
Blood - cytopenia
Marrow - hypocellular
What are some differential diagnoses for pancytopenia and hypocellular marrow
Hypoplastic MDS / AML
Hypocellular acute lymphoblastic leukaemia
Hairy cell leukaemia
Mycobacterial (usually atypical) infection
Anorexia nervosa
Idiopathic thrombocytopenic purpura
What is the Camitta criteria for severe aplastic anaemia?
2 out of 3 peripheral blood features: 1. Reticulocytes <1% (<20 x 10^9/L) 2. Neutrophils <0.5 x 10^9/L 3. Platelets <20 x 10^9/L \+ Bone marrow <25% cellularity
What are the steps to bone marrow failure treatment?
Seek and remove cause Supportive Immunosuppressive Drugs to promote recovery of marrow Step cell transplantation
What immunosuppressive therapy is given in bone marrow failure?
Anti-thymocyte globulin
Steroids
Eltrombopag
Cyclosporine A
What drugs are given to promote marrow recovery?
Oxymethone, TPO receptor agonists
What specific treatment is there for aplastic anaemia?
Immunosuppressive therapy - older patient ○ Anti-lymphocyte globulin (ALG) ○ Ciclosporin ○ Eltrombopag • Androgens - oxymethalone • Stem cell transplantation ○ Younger patient with donor (80% cure) VUD/MUD >40 years (50% survival)
What are the features of supportive aplastic anaemia treatment?
Blood products
Antimicrobials
Iron chelation therapy
What late complications may occur following immunosuppressive therapy for AA?
Relapse of AA
Clonal haematological disorders: myelodysplasia, leukaemia
Solid tumours
What congenital malformations may occur in 60-70% of children with Fanconi’s Anaemia?
Short stature Hypopigmented spots and café-au-lait spots Abnormality of thumbs Microcephaly or hydrocephaly Hypogonadism Developmental delay No abnormalities in 30%
What are the complications of Fanconi’s anaemia?
Aplastic anaemia Leukaemia Liver disease Myelodysplasia Cancer
What is dyskeratosis congenita?
An inherited disorder characterised by: bone marrow failure, cancer predisposition and somatic abnormalities
What is Fanconi’s anaemia?
Most common form of inherited aplastic anaemia
Autosomal recessive or X-linked inheritance
What is the presentation of dyskeratosis congenita?
Skin pigmentation
Nail dystrophy
Leukoplakia
