Myeloproliferative disorders Flashcards
What does myeloproliferative mean?
- Myelo = bone marrow lineage (granulocytes, red cells and platelets)
- Proliferative = rapidly multiplying
What are chronic myeloproliferative disorders?
- Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells
- In contrast to acute leukaemia, maturation is relatively preserved
What does this blood film show?
Normal blood film
What does this blood film show?
Acute leukaemia
What does this blood film show?
Myeloproliferative disorder
How are myeloproliferative disorders divided into sub-types?
Presence of BCR-ABL1
What are examples of each of the sub-types of myeloproliferative disorders?
- BCR-ABL1 positive = chronic myeloid leukaemia
- BCR-ABL1 negative = polycythaemia rubra vera, essential thrombocythaemia, idiopathic myelofibrosis
In basic terms what is chronic myeloid leukaemia?
Over production of myeloid cells - granulocytes and their precursors +/- other lineages e.g. platelets
In basic terms what is polycythaemia rubra vera?
Over-production of red cells
In basic terms what is essential thrombocythaemia?
Over-production of platelets
What blood results and signs would make you suspect in a MPD?
- High granulocyte count +/-
- High RBC count/Hb +/-
- High platelet count +/-
- Eosinophilia/basophilia
- Splenomegaly
- Thrombosis in an unusual place
Describe the chronic phase of CML
- Previously, chronic phase with intact maturation for 3-5 years, followed by blast crisis reminiscent of acute leukaemia with maturation defect
- Fatal without stem cell/bone marrow transplantation in the chronic phase
What are the 3 stages of CML?
- Chronic phase
- Accelerated phase
- Blast crisis
What are the clinical features of CML?
Asymptomatic, splenomegaly, hypermetabolic symptoms, gout, priapism
What are some of the expected lab features of CML?
- Blood count: Normal/decreased Hb
- Leucocytosis with neutrophilia and myeloid precursors, eosinophilia, basophilia
- Thrombocytosis
- Bone marrow
What is the hallmark of CML?
Philadelphia chromosome
What happens as a result of the Philadelphia chromosome?
- Results in a new gene BCR-ABL1
- The gene product is a tyrosine kinase which causes abnormal phosphorylation leading to the haematological changes in CML
What drug is used to target the gene product of CML?
- Imatinib - tyrosine kinase inhibitor
- Usually good response to this
What are some clinical features common to all MPDs?
- Increased cell turnover - gout, fatigue, weight loss, sweats
- Symptoms/signs due to splenomegaly
- Marrow failure - fibrosis or leukaemic transformation
- Thrombosis - arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication
What is the disease mechanism involved in polycythaemia rubra vera (PRV)?
- High Hb/haematocrit accompanied by erythrocytosis but can have excessive production of other lineages
- Important to distinguish from secondary polycythaemia (chronic hypoxia, smoking, epo-secreting tumour) and pseudopolycythaemia (dehydration, diuretic therapy. obesity)
What are the clinical features of PRV?
- Clinical features common to MPD
- Headache, fatigue - remember blood viscosity is raised not plasma viscosity
- Aquagenic puritis (itch)
How is PRV investigated?
- History + examination
- FBC, blood film
- JAK2 mutation status
- Investigation for secondary/pseudo causes e.g. CXR, ABGs, drug history
- Can do epo levels and bone marrow biopsy
What is JAK2 mutation?
- JAK2 = kinase
- JAK2 mutations are present in over 95% of these patients
- The mutation results in loss of auto-inhibition
- Activation of erythropoiesis in the absence of ligand
- Mutational analysis forms part of initial screening and has replaced a number of other tests in routine practice
How is PRV treated?
- Vensect to haematocrit <0.45
- Aspirin
- Cytotoxic oral chemotherapy e.g. hydroxycarbamide
