Leukaemia (CH) Flashcards
What is leukaemia?
Uncontrolled proliferation of immature WBCs that then accumulate in the blood or bone marrow
Describe how haematopoietic stem cells –> blood cells (recap)
- multipotential haematopoietic stem cell –> common myeloid progenitor + common lymphoid progenitor
- common myeloid progenitor –> megakaryocyte (–> thrombocytes), erythrocyte, mast cell, myeloblast (–> basophil, neutrophil, eosinophil, monocyte–>macrophage)
- common lymphoid progenitor –> natural killer cell (large granular), small lymphocyte –> T lymphocyte + B lymphocyte–>plasma cell
What are the four types of leukaemia?
- acute lymphoblastic leukaemia (ALL)
- acute myeloid leukaemia (AML)
- chronic lymphocytic leukaemia (CLL)
- chronic myeloid leukaemia (CML)
Acute = problem with progenitors
Chronic = problem with mature cells
What are the typical symptoms of leukaemia? (11)
- fatigue
- weight loss
- fever
- pallor
- ecchymoses
- petechiae
- bleeding
- dyspnoea
- dizziness
- palpitations
- recurrent infections
What does the management of leukaemia generally involve? (2)
- chemotherapy +/- radiotherapy
- stem cell transplantation
What is acute lymphoblastic leukaemia (ALL)?
Lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation
Who does acute lymphoblastic leukaemia (ALL) occur most in?
Children 2-5 years old –> most common malignant disease in children
M>F
What condition increases the risk of acute lymphoblastic leukaemia (ALL)?
Down syndrome
What do most patients with acute lymphoblastic leukaemia (ALL) usually have on presentation?
Signs and symptoms related to cytopenias (e.g. fatigue, easy bruising) and enlarged lymph nodes
What is acute lymphoblastic leukaemia (ALL) characterised by?
Early lymphoid precursors replacing the normal HSCs of the bone marrow and further infiltrating various body organs
What are the clinical features of acute lymphoblastic leukaemia (ALL)? (9)
- bone pain (secondary to BM infiltration)
- lymphadenopathy
- hepatomegaly
- splenomegaly
- fever
- testicular swelling
- anaemia - lethargy and pallor
- thrombocytopenia - ecchymoses, petechiae, epistaxis, menorrhagia
- neutropenia - recurrent infections
What distinguishes ALL from AML?
Lymphadenopathy and fevers (not seen in AML)
What investigations do we do for acute lymphoblastic leukaemia (ALL)? (3)
- FBC - neutropenia, thrombocytopenia, anaemia (normocytic), leukocytosis
- peripheral blood smear - lymphoblasts (immature WBCs)
- bone marrow aspiration and biopsy (confirms diagnosis) - hypercellular marrow with >20% of cells being lymphoblasts
How do we manage newly diagnosed acute lymphoblastic leukaemia (ALL)? (2)
- dexamethasone
- cyclophosphamide
How do we manage acute lymphoblastic leukaemia (ALL) with positive Philadelphia chromosome?
Tyrosine kinase inhibitor (imatinib)
How do we manage acute lymphoblastic leukaemia (ALL) in remission?
Cyclophosphamide, stem cell transplant
How do we manage a relapse of acute lymphoblastic leukaemia (ALL)?
Salvage chemotherapy (blinatumomab), stem cell transplantation
What is chronic lymphocytic leukaemia (CLL)?
Low-grade B-cell lymphoma caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B cells
What is the median age at diagnosis of chronic lymphocytic leukaemia (CLL)?
70-72 years old - most common leukaemia in adults
What is a rare complication of chronic lymphocytic leukaemia (CLL)?
Richter transformation - sudden transformation of CLL into a significantly more aggressive form of large cell non-Hodgkin’s lymphoma
- lymph node swelling
- fever
- weight loss
- night sweats
What cells do you see in chronic lymphocytic leukaemia (CLL)?
Smudge cells - remnant of cells that have no identifiable plasma membrane or nuclear structure
How is chronic lymphocytic leukaemia (CLL) often found?
Incidental finding
What are the clinical features of chronic lymphocytic leukaemia (CLL)? (7)
- B symptoms - weight loss, fever, anorexia
- lymphadenopathy - more marked than CML
- splenomegaly / hepatomegaly
- pruritus
- thrombocytopenia = bleeding
- recurrent infections (hypogammaglobulinaemia)
- anaemia - SOB, fatigue
Why do patients often have a late diagnosis of chronic lymphocytic leukaemia (CLL)?
Many cases remain asymptomatic for a long period of time - incidental finding
What investigations do we do for chronic lymphocytic leukaemia (CLL)? (3)
- FBC - persistent lymphocytosis with high % of small, mature lymphocytes, anaemia, thrombocytopenia
- blood smear - smudge/smear cells (and spherocytes and polychromasia if haemolysis)
- features on bloods of anaemia - warm AIHA, IgG
How do we manage chronic lymphocytic leukaemia (CLL)?
- asymptomatic early stage - watchful waiting
- advanced/symptomatic - chemotherapy
- relapse - allogenic stem cell transplant
What is acute myeloid leukaemia (AML)?
Life-threatening haematological malignancy caused by clonal expansion of myeloid blasts in the BM, peripheral blood and/or extramedullary tissues
Who does acute myeloid leukaemia (AML) occur most in?
65 years old - most common acute leukaemia in adults
What is the most common cause of acute myeloid leukaemia (AML)?
Pre-existing haematopoietic disorders e.g. aplastic anaemia, myeloproliferative disorders like polycythaemia vera
What usually progresses to acute myeloid leukaemia (AML)?
1/3 of myelodysplasia progresses to AML
What is seen on cytology in acute myeloid leukaemia (AML)?
Auer rods - large pink/red stained needle-like structures
What condition is acute myeloid leukaemia (AML) associated with?
Down syndrome
What are the clinical features of acute myeloid leukaemia (AML)?
- anaemia - fatigue, pallor, weakness
- neutropenia (despite high WCC) - frequent infection
- thrombocytopenia - epistaxis, bleeding gums, petechiae, purpura, easy bruising
- splenomegaly - ‘early satiety’
- bone pain
What investigations are done for acute myeloid leukaemia (AML)?
- FBC - neutropenia, thrombocytopenia, anaemia, leukocytosis
- peripheral blood smear - myeloblasts (immature WBCs) and Auer rods
- bone marrow aspiration and biopsy (confirms diagnosis) - >20% blasts, Auer rods
How do we manage acute myeloid leukaemia (AML)?
- hydration, hydroxycarbamide, allopurinol
- chemotherapy, cytarabine, stem cell transplant
What indicates poor prognosis in acute myeloid leukaemia (AML)? (3)
- age >60
- > 20% blasts after first chemotherapy
- depletion of chromosomes 5 or 7
What is chronic myeloid leukaemia (CML)?
Overexpression of cells of myeloid lineage, especially granulocytes
When is peak incidence of chronic myeloid leukaemia (CML)?
50-60 years old
What chromosome is seen in chronic myeloid leukaemia (CML)?
- Philadelphia chromosome in >95%
- reciprocal translocation between chromosome 9 and 22
- resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal
What are the clinical features of chronic myeloid leukaemia (CML)? (5)
- B symptoms - weight loss, fever, night sweats
- massive splenomegaly
- anaemia
- hyperviscosity symptoms - increased thrombotic risk
- gout
What investigations do we do for chronic myeloid leukaemia (CML)? (4)
- FBC - leukocytosis, thrombocytosis, basophilia, eosinophilia, high band cells
- blood film - left shift (immature granulocytes) –> granulocytosis + myeloblasts
- decreased leukocyte alkaline phosphatase (LAP)
- cytogenic testing - for confirmation of Philadelphia chromosome
What is the first-line treatment for chronic myeloid leukaemia (CML)?
Tyrosine kinase inhibitors (Imantinib)
What is a complication of treatment with chemotherapy (leukaemia)?
Tumour lysis syndrome: PUKE calcium (E = elevated)
- hyperPhosphataemia
- hyperUricaemia
- hyperKalaemia
- hypercalcaemia
How do we diagnose tumour lysis syndrome?
- PUKe calcium +
- increased serum creatinine OR
- cardiac arrhythmia OR
- seizure
What can be used as prophylaxis against tumour lysis syndrome?
Allopurinol
Give an example of a patient who would need immediate specialist referral for urgent FBC (leukaemia)?
0-24 years old with unexplained petechiae or hepatosplenomegaly
How can we interpret bloods in leukaemia?
- look at lymphocytes
- look at WBC
- others - blasts, bands
E.g.
1. low lymphocytes = AML or CML
2. WBC>100 = chronic = consider CML
3. presence of band cells = confirm CML
How can we differentiate between acute and chronic myeloid leukaemias?
- blasts = AML
- bands = CML
Summary of the four types of leukaemia.
- AML - immature myeloid WBCs - anaemia, spontaneous bleeding - adults and children
- CML - myeloid stem cells - anaemia, low platelets, splenomegaly - rare in children
- ALL - immature B/T cells and macrophages - disturb BM function - children
- CLL - lymphoid B/T cell - lymphadenopathy, splenomegaly - over 55s