CML and myeloproliferative disorders Flashcards
what is a myeloproliferative disorder
clonal prolif of 1 or more haematopoietic components (inc production of mature cells)
classified based on dominant cell line involved
what translocation is associated with the philidelphia chromosome
9,22
what myeloproliferative disorders are philidelphia Chr pos and neg
\+ve = CML -ve = polycythemia vera, essential thrombosis, myelofibrosis
what is the significance of the JAK2 mutation
asso with philidelphia Chr -ve MPDs
asso with 95% of PolyVera cases
findings in polycythemia
inc RBC mass, inc Hb, inc packed cell vol
causes of polycythemia
primary = PolyVera, familial poly
secondary (due to inc EPO) = inc altitude, chronic hypoxia (COPD), drugs
Pseudo = dec plasma vol, dehydration, D&V, burns
how will polycythemia ruba vera present
hyperviscosity, hypervol, hypermetabolism
-> blurred vision, headache, red nose, gout, thrombosis/stroke, splenomeg
Itchy after contact with water
what mutation is associated with polycythemia RV
JAK2 V617F point mut
investigative findings in polycythemia RV
inc HB, inc Hct, dec circulating EPO
BM dominated by erythoid precursors
treatment and maintenance of polycythemia ruba Vera
Tx = venesection maintenance = hydroxycarbamide, aspirin
what are the clinical features of essential thrombosis
often incidental findings
venous/arterial thrombosis, gangrene, haemorrhage, headache, dizziness, visual disturbances
what are the investigative findings in essential thrombosis
platelets sustained >600
megakaryocytes dominate BM
blood film - large platelets and megakaryocyte fragments
Nb 50% associated with JAK2
treatment for essential thrombosis
aspirin
anagrelide (dec plt formation)
hydroxycarbamide
pathology of myelofibrosis
MPD mainly of megakaryocytes and granulocytic cells
-> reactive BM fibrosis with extramedullary haematopoiesis
causes of myelofibrosis
primary - 50% = JAK2
secondary - leukemia, hypoparathyroidism, drugs
Clinical features of myelofibrosis
extramedullary haematopoiesis -> hepatomeg + massive splenomeg, weight loss, fever
often presents in elderly, may be with Budd-Chiari syndrome (abdo pain, ascites, hepatomeg)
investigative findings in myelofibrosis
film = tear drop poikilocytes, leukoerythroblasts Bm = dry tap (due to fibrosis)
treatment for myelofibrosis
supportive
SCT
Ruxolitinib = JAK2 inhib
hydroxycarbamide, thialidamide, steroids
how will CML present
80% = asymptomatic
hepatomeg + massive splenomeg, lethargy, hypermetabolism, easy bruisiing/bleeding
investigative findings in CML
blood film - massive leukocytosis, no excess myeloblasts in bone marrow (<5%)
FISH - phil Chr +ve
inc basophils
what is the Philadelphia Chr fusion geen
BCR-ABL
what are the different stages of CML
1 - chronic phase. <5%blasts sin BM/blood
Tx = imatinib (BCR_ABL TKI)
2 - accelerated phase. >10% blasts in BM/blood. inc manifestations
3 - blast phase. >20% blasts, resembles acute leukemia, Tx similar to AML
