Myeloproliferative Disorders and CLL Flashcards
What translocation drives CML?
Philadelphia chromosome +ve, (9;22)
What does the BCR-ABL gene cause?
Increased tyrosine kinase activity- which is why treatment is imatinib (BCR-ABL tyrosine kinase inhibitor)
What is CML?
A myeloproliferative disorder.
Neoplastic proliferation of myeloid cells, especially granulocytes and their precursors; basophils are characteristically increased.
Age group typically affected by CML?
MIDDLE AGED 40-60
Common feature of CML?
SPLENOMEGALY
When is imatinib treatment for CML most effective?
Chronic phase
Blood results for CML?
Neutrophilia
Raised WCC
Blood film of CML?
LEFT SHIFT- high number of young immature white blood cells
Leukocytosis
Eosiniophilia
Basophilia
Hypoblated megakaryocytes in bone marrow
Diagnosis of CML?
Use FISH currently, PCR for BCR-ABL1 fusion gene resulting form t(9;22), forming philadelphia chromosome.
Phases of CML and features?
Chronic- responsive to therapy <5% blasts
Accelerated- >10% blasts, less responsive to therapy, increasing manifestations such as splenomegaly
Blast phase: >20% blasts behaves like Acute leukaemia, treatment similar to AML possibly with allogeneic SCT for young people.
Bone marrow of CML?
HYPERCELLULAR BM with spectrum of immature (myelocytes) and mature granulocytic cells in the blood.
Blood film of CLL?
SMEAR CELLS/SMUDGE CELLS
Remember SMEAR CLLs
High WBC with lymphocytosis
Difference between CLL and small lymphocytic leukaemia (SLL)?
Essentially the SAME disease process but CLL primarily seen in the bone marrow
SLL in the LYMPH NODES (generalised lymphadenopathy)
Age range affected by CLL and gender more commonly affected?
Elderly >50
Twice as common in MALES
What is CLL associated with?
Autoimmune haemolytic anaemia and ITP
Staging of CLL?
Binet staging A, B &C
A: High WBC, <3 groups of enlarged lymph nodes
Usually no treatment needed
B: >3 groups of enlarged lymph nodes (consider treating)
C: Anaemia or thrombocytopenia (treat)
What is richter syndrome?
Transformation of CLL to aggressive disease- diffuse large B cell lymphoma
What is CLL?
A lymphoproliferative disease, neoplastic proliferation of naive B cells.
Philadelphia chromosome negative myeloproliferative disorders?
Polycythemia vera
Myelofibrosis
Essential thrombocytosis
What is essential thrombocythaemia?
A myeloproliferative disorderw here megakaryocytes dominate the bone marrow.
Gene mutation associated with essential thrombocythaemia?
JAK2 mutation in 50%
Clinical features of essential thrombocythaemia?
Venous and arterial thrombnosis & haemorrhage
Either platelets over functioning or not functioning.
Blood film and bone marrow of myelofibrosis?
TEAR DROP POIKILOCYTES (DACROCYTE), LEUKOERYTHROBLASTIC SMEAR (tear drop RBCs, nucleated RBCs, immature granulocytes)
BM0 fibrosis, ‘dry tap’
What is myelofibrosis?
A myeloproliferative disorder with fibrosis of bone marrow, reduced production of all cell lineages, pancytopenia.
Mutation in myelofibrosis?
JAK2 present in 50%
Clinical features of myelofibrosis?
Extramedullary haematopoieosis: MASSIVE SPLENOMEGALY, hepatomegaly, weight loss, fever
Mutation in polycythaemia vera?
JAK2 MUTATION IN 95%!!!
A secondary cause of polycythaemia?
Raised EPO- so disease state such as RENAL CELL CARCINOMA GET ECTOPIC EPO
High altitude, chronic hypoxia e.g. COPD
Clinical features of polycythaemia rubra vera?
Blurred vision, headache
Thrombosis
Histamine release>aquagenic pruritis (itching after bathing)
Most common cause of Budd-chiari
Investigation results for Polycythaemia vera?
Raised Hb
Raised haematocrit
Treatment for polycythaemia rubra vera?
Venesection (reduces RBC mass)
Hydroxycarbamide to lower count
Which Haem disorders present with MASSIVE splenomegaly?
CML and myelofibrosis
Both myeloproliferative disorders!
What is tumour lysis syndrome?
Combination of metabolic and electrolyte abnormalities that occur in patients with cancer after initiation of cytotoxic treatment but also spontaneously. Characterised by excessive cell lysis resulting in HYPERURICAEMIA, HYPERPHOSPHATAEMIA, HYPERKALAEMIA and HYPOCALCAEMIA. Most common with LYMPHOMAS and LEUKAEMIAS, in particular BURKITT’s LYMPHOMA and ALL.
