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Leukaemia (CH) Flashcards

1
Q

What is leukaemia?

A

Uncontrolled proliferation of immature WBCs that then accumulate in the blood or bone marrow

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2
Q

Describe how haematopoietic stem cells –> blood cells (recap)

A
  • 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
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3
Q

What are the four types of leukaemia?

A
  • 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

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4
Q

What are the typical symptoms of leukaemia? (11)

A
  • fatigue
  • weight loss
  • fever
  • pallor
  • ecchymoses
  • petechiae
  • bleeding
  • dyspnoea
  • dizziness
  • palpitations
  • recurrent infections
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5
Q

What does the management of leukaemia generally involve? (2)

A
  • chemotherapy +/- radiotherapy
  • stem cell transplantation
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6
Q

What is acute lymphoblastic leukaemia (ALL)?

A

Lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation

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7
Q

Who does acute lymphoblastic leukaemia (ALL) occur most in?

A

Children 2-5 years old –> most common malignant disease in children

M>F

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8
Q

What condition increases the risk of acute lymphoblastic leukaemia (ALL)?

A

Down syndrome

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9
Q

What do most patients with acute lymphoblastic leukaemia (ALL) usually have on presentation?

A

Signs and symptoms related to cytopenias (e.g. fatigue, easy bruising) and enlarged lymph nodes

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10
Q

What is acute lymphoblastic leukaemia (ALL) characterised by?

A

Early lymphoid precursors replacing the normal HSCs of the bone marrow and further infiltrating various body organs

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11
Q

What are the clinical features of acute lymphoblastic leukaemia (ALL)? (9)

A
  • bone pain (secondary to BM infiltration)
  • lymphadenopathy
  • hepatomegaly
  • splenomegaly
  • fever
  • testicular swelling
  • anaemia - lethargy and pallor
  • thrombocytopenia - ecchymoses, petechiae, epistaxis, menorrhagia
  • neutropenia - recurrent infections
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12
Q

What distinguishes ALL from AML?

A

Lymphadenopathy and fevers (not seen in AML)

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13
Q

What investigations do we do for acute lymphoblastic leukaemia (ALL)? (3)

A
  • 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
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14
Q

How do we manage newly diagnosed acute lymphoblastic leukaemia (ALL)? (2)

A
  • dexamethasone
  • cyclophosphamide
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15
Q

How do we manage acute lymphoblastic leukaemia (ALL) with positive Philadelphia chromosome?

A

Tyrosine kinase inhibitor (imatinib)

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16
Q

How do we manage acute lymphoblastic leukaemia (ALL) in remission?

A

Cyclophosphamide, stem cell transplant

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17
Q

How do we manage a relapse of acute lymphoblastic leukaemia (ALL)?

A

Salvage chemotherapy (blinatumomab), stem cell transplantation

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18
Q

What is chronic lymphocytic leukaemia (CLL)?

A

Low-grade B-cell lymphoma caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B cells

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19
Q

What is the median age at diagnosis of chronic lymphocytic leukaemia (CLL)?

A

70-72 years old - most common leukaemia in adults

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20
Q

What is a rare complication of chronic lymphocytic leukaemia (CLL)?

A

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
21
Q

What cells do you see in chronic lymphocytic leukaemia (CLL)?

A

Smudge cells - remnant of cells that have no identifiable plasma membrane or nuclear structure

22
Q

How is chronic lymphocytic leukaemia (CLL) often found?

A

Incidental finding

23
Q

What are the clinical features of chronic lymphocytic leukaemia (CLL)? (7)

A
  • B symptoms - weight loss, fever, anorexia
  • lymphadenopathy - more marked than CML
  • splenomegaly / hepatomegaly
  • pruritus
  • thrombocytopenia = bleeding
  • recurrent infections (hypogammaglobulinaemia)
  • anaemia - SOB, fatigue
24
Q

Why do patients often have a late diagnosis of chronic lymphocytic leukaemia (CLL)?

A

Many cases remain asymptomatic for a long period of time - incidental finding

25
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
26
How do we manage chronic lymphocytic leukaemia (CLL)?
- asymptomatic early stage - watchful waiting - advanced/symptomatic - chemotherapy - relapse - allogenic stem cell transplant
27
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
28
Who does acute myeloid leukaemia (AML) occur most in?
65 years old - most common acute leukaemia in adults
29
What is the most common cause of acute myeloid leukaemia (AML)?
Pre-existing haematopoietic disorders e.g. aplastic anaemia, myeloproliferative disorders like polycythaemia vera
30
What usually progresses to acute myeloid leukaemia (AML)?
1/3 of myelodysplasia progresses to AML
31
What is seen on cytology in acute myeloid leukaemia (AML)?
Auer rods - large pink/red stained needle-like structures
32
What condition is acute myeloid leukaemia (AML) associated with?
Down syndrome
33
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
34
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
35
How do we manage acute myeloid leukaemia (AML)?
- hydration, hydroxycarbamide, allopurinol - chemotherapy, cytarabine, stem cell transplant
36
What indicates poor prognosis in acute myeloid leukaemia (AML)? (3)
- age >60 - >20% blasts after first chemotherapy - depletion of chromosomes 5 or 7
37
What is chronic myeloid leukaemia (CML)?
Overexpression of cells of myeloid lineage, especially granulocytes
38
When is peak incidence of chronic myeloid leukaemia (CML)?
50-60 years old
39
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
40
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
41
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
42
What is the first-line treatment for chronic myeloid leukaemia (CML)?
Tyrosine kinase inhibitors (Imantinib)
43
What is a complication of treatment with chemotherapy (leukaemia)?
Tumour lysis syndrome: PUKE calcium (E = elevated) - hyperPhosphataemia - hyperUricaemia - hyperKalaemia - hypercalcaemia
44
How do we diagnose tumour lysis syndrome?
- PUKe calcium + - increased serum creatinine OR - cardiac arrhythmia OR - seizure
45
What can be used as prophylaxis against tumour lysis syndrome?
Allopurinol
46
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
47
How can we interpret bloods in leukaemia?
1. look at lymphocytes 2. look at WBC 3. others - blasts, bands E.g. 1. low lymphocytes = AML or CML 2. WBC>100 = chronic = consider CML 3. presence of band cells = confirm CML
48
How can we differentiate between acute and chronic myeloid leukaemias?
- blasts = AML - bands = CML
49
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

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