Chronic Myeloproliferative Disorders Flashcards
What is meant by myeloproliferative?
The bone marrow makes too many red blood cells, platelets, or certain white blood cells
What are CMDs?
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 are the sub types of MPDs?
BCR-ABL1 +ve: CML
BCR-ABL1 -ve: Polycythaemia Rubra Vera, Essential Thrombocytaemia, Idiopathic Myelofibrosis
When should a MPD be considered?
High Granulocyte count High Red cell count / haemoglobin High Platelet count Eosinophilia/basophilia Splenomegaly Thrombosis in an unusual place No reactive explanation
What occurs in CML?
Proliferation of myeloid cells- granulocytes and their precursors, other lineages (platelets)
Previously, chronic phase with intact maturation 3-5y, followed by blast crisis reminiscent of acute leukaemia with maturation defect
Fatal without stem cell/bone marrow transplantation in chronic phase
What are the clinical features of CML?
Asymptomatic Splenomegaly Hypermetabolic symptoms Gout Misc: Problems related to hyperleucocytosis problems, Priapism
What are the lab features of CML?
Blood count changes:
normal/↓Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
Bone marrow- increase in myelocytes and eosinophils
What is the hallmark of CML?
Philadelphia chromosome
What is the gene product in CML?
Tyrosine kinase which causes abnormal phosphorylation (signalling) leading to the haematological changes in CML
What features are common to both BCR-ABL1 + and - MPD?
Asymptomatic
Increased cellular turnover (gout, fatigue, weight loss, sweats)
Symptoms/signs due to splenomegaly
Marrow failure (fibrosis or leukaemic transformation:lower with PRV and ET)
Thrombosis (arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia)
What occurs in PRV?
High haemoglobin/haematocrit accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages
What is it important to distinguish PRV from?
Secondary polycythaemia (chronic hypoxia, smoking, erythropoietin-secreting tumour etc) Pseudopolycythaemia (eg dehydration, diuretic therapy, obesity)
What are the clinical features of PRV?
Common to MPD
Headache, fatigue (blood viscosity raised not plasma viscosity)
Itch (aquagenic puritis)
How is polycythaemia investigated?
History (eg history suggestive of a secondary polycythaemia?)
Examination (eg splenomegaly?)
FBC, film
JAK2 mutation status
Ix for 2’/pseudo causes- CXR, O2 saturation/ABGs, DHx)
Infrequently EPO levels, bone marrow biopsy
How many PRV patients have a JAK2 (kinase) mutation?
95%
What does the JAK2 mutation?
Mutation (substitution) results in loss of auto-inhibition
Activation of erythropoiesis in absence of ligand
How is PRV treated?
Venesect to haematocrit <0.45
Aspirin
Cytotoxic oral chemo (hydroxycarbamide)
What is essential thrombocythaemia (ET)?
Uncontrolled production of abnormal platelets
What can the abnormal platelet function in ET cause?
Thrombosis
At high levels also bleeding due to acquired vWD
What are the clinical features of ET?
Common to MPD (particularly vasoocclusive complications)
Bleeding
How is ET diagnosed?
Exclude reactive thrombocytosis
(Blood loss, inflammation, malignancy, iron deficiency)
Exclude CML
Genetics: JAK2 mutations (in 50%), CALR (Calreticulin) in those without mutant JAK2, MPL mutation
Characteristic bone marrow appearances
What is the treatment for ET?
Anti-platelet agents- Aspirin
Cytoreductive therapy to control proliferation- hydroxycarbamide, anagrelide, interferon alpha
What occurs in idiopathic myelofibrosis?
Marrow failure (variable degrees)
Bone marrow fibrosis (no secondary fibrosis)
Extramedullary hematopoiesis (liver and spleen)
Leukoerythroblastic film appearances
Teardrop-shaped RBCs in peripheral blood
What are the clinical features of MF?
Marrow Failure- anaemia, bleeding, infection
Splenomegaly- LUQ abdo pain, complications including portal HT
Hypercatabolism
Common to MPD
How is MF diagnosed?
Lab diagnosis Typical blood film (tear-drop shaped RBC and leucoerythroblastic) Dry aspirate Fibrosis on trephine biopsy JAK2 or CALR mutation in a proportion
What are the two types of MF?
Idiopathic(or agnogenic myeloid metaplasia)
Post-polycythaemia or essential thrombocythaemia
What are the causes for a leucoerythroblastic film?
Reactive (sepsis)
Marrow infiltration
Myelofibrosis
What is the treatment for MF?
Supportive care (blood transfusion, platelets, antibiotics)
Allogeneic stem cell transplantation in a select few
Splenectomy (Controversial)
JAK2 inhibitors e.g. Ruxolitinib (improve spleen size, QoL, ?survival)
