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Glasgow Phase 3 > Acute and Chronic Leukaemia > Flashcards

Acute and Chronic Leukaemia Flashcards

1
Q

What is the classification of leukaemia?

A

Either myeloid (immune cells) or lymphoid (B/T cells). and either acute or chronic

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2
Q

What causes leukaemia?

A

acquired genetic abnormalities

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3
Q

What are the definitions of acute/chronic leukaemia?

A

Acute leukaemia is a neoplastic disorder of immature cells (blasts) in the bone marrow. Symptoms come from marrow failure.
Chronic leukaemia is a neoplastic disorder or mature WBCs in the bone marrow. Symptoms come from accumulation of cells

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4
Q

What are the two pre-leukaemic disorders?

A

Myelodysplastic syndrome
Myeloproliferative disease

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5
Q

What are the characteristics of myelodysplastic syndrome?

A
  • Failure of effective haematopoiesis as cells produced are dysplastic. It results in marrow failure as the cells are non-functional.
  • 25% progress to acute myeloid leukaemia. The risk depends on proportion of blast cells in marrow, the number and severity of cytopenias and the cytogenetic profile
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6
Q

What are the characteristics of myeloproliferative disorders

A

JAK2 mutation is prevalent. It is characterised by ineffective haematopoiesis which can cause essential thrombocytopenia, polycythaemia vera (primary polycythaemia) which have a risk of vascular events but low risk of progression to AML, or myelofibrosis

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7
Q

What is myelofibrosis?

A

A serious condition which results in the overproduction of fibrous tissue. It results in a large spleen and systemic symptoms. Incurable other than a stem cell transplant. Also can used JAK2 inhibitors

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8
Q

What are the causes of acute leukaemia?

A

Largely unknown but thought to be:
- Chemicals,
- Chemotherapy,
- Radiotherapy,
- Genetic (downs or fanconi anaemia)
- Antecedent blood disorders
- Infection?

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9
Q

How is the diagnosis of AL made?

A

From history if there is a rapid onset of symptoms, lethargy, infections, bleeding and bruising, bone pain, gum swelling, lymphadenopathy or skin rash.
In the blood there will be anaemia, neutropenia, thrombocytopenia and blast cells,.
In the bone marrow blast cells will be>20% of cells

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10
Q

What is a specific histological finding of M3 acute myeloid leukaemia and what is the genetic abnormality?

A

Rods in the cytoplasm of cells. It is a translocation of the 15th and 17th chromosome. It is associated with DIC and needs treated immediately. Also called Acute promyelocytic leukaemia

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11
Q

What is the importance of cytogenetics in acute myeloid leukaemia?

A

Understanding the genetic mutation is essential for determining prognosis. Certain abnormalities correlate with response to treatment and survival. It also allows decisions on management,

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12
Q

What is the management of acute myeloid leukaemia

A
  1. Intensive chemotherapy (Anthracycline and cytarabine based) +/- SCT (<60-65yrs). Aim is to eradicate the abnormal clone.
  2. Low dose chemotherapy (pts >60-65),
  3. Supportive care only (older pts or with major co-morbidities. Prognosis 3-6 months)
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13
Q

What are the side effects of chemotherapy?

A

Heavy myelotoxicity (immune system supression)
Hair loss,
Sterility,
Mucositis

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14
Q

What is the clinical presentation of Acute lymphoblastic leukaemia

A
  • Purpuric rash,
  • Limping child,
  • Unexplained bone pains
  • Fatigue and SOB,
  • Recurrent infections,
  • Abnormal bleeding,
  • Night sweats
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15
Q

Name an example of a genetic mutation that can cause acute lymphoblastic leukaemia

A

t(9:22) - Philadelphia chromosome

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16
Q

Describe the management of acute lymphoblastic leukaemia

A
  • Steroids and aggressive chemotherapy
  • For relapsed patients can use CAR T cells (modified cells that have receptors which recognise the tumour cell, creating an immune reaction, killing the cancer cell) or Blinatumomab
17
Q

What is the supportive management for acute leukaemia?

A
  • Blood transfusion for symptomatic patients, improves QOL.
  • Fresh frozen plasma for coagulopathy/DIC,
  • Platelet transfusion to try reduce bleeding problems.
  • Antibiotics,
  • Granulocyte growth factor
18
Q

What are the indications for a stem cell transplant in acute leukaemia

A
  • Relapsed patients,
  • Those with high risk molecular profile,
  • Age less than 60 years,
  • Good performance (fit enough for the procedure)
19
Q

Describe features and the presentation of chronic lymphocytic leukaemia

A
  • Commonest leukaemia which is more likely to affect males. B CLL is commonest. It is a complex disease
  • Can present with no symptoms so incidental diagnosis is common, or can present with lethargy, night sweats weight loss, symptoms of anaemia, lymphadenopathy or infection
20
Q

Explain the diagnosis of chronic lymphocytic leukaemia

A
  • Clonal populations of B lymphocytes with specific patterns of markers.
  • They express a unique immunophenotype which can be picked up on flow cytometry.
21
Q

Explain the clinical staging of chronic leukaemia

A

Stage A - Less than 3 involved nodes (survival 10yrs)
Stage B - More than 3 involved nodes, liver and spleen (survival 7yrs)
Stage C - Anaemia or thrombocytopenia (2 yrs)

22
Q

Explain the use of cytogenetics in CLL

A

It can identify genetic mutations which have given rise to the cancer. For example 17p deletions cause an aggressive disease due to the loss of the p53 gene (TSG) and it doesn’t respond as well to chemotherapy by may respond to steroids and antibiotics. Therefore cytogenetics can guide treatment choices and allow for use of more targeted biological therapies.

23
Q

What are some immune complications that can arise with CLL?

A
  • Autoimmune haemolytic anaemia
  • Autoimmune thrombocytopenia
  • Treat with steroids
24
Q

Why can the risk of infection increase with CLL

A

It can cause:
- Hypogammaglobinaemia (not enough antibodies produced),
- Cell mediated immunity is impaired,
- T lymphopenia,
- Neutropenia
- Defects in complement activation.
This can all increase patients risk of developing a range of infections which can be just as life threatening

25
Q

What would trigger you to treat a patient with CLL

A
  • You don’t treat asymptomatic patients, you watch and wait.
  • If patient is symptomatic (sweats, weight loss or symptomatic nodes) or has bone marrow failure (indicated by anaemia or thrombocytopenia) then you treat
26
Q

Describe the presentation of chronic myeloid leukaemia

A

May be asymptomatic,
- Night sweats,
- Weight loss,
- Fatigue,
- Abdominal discomfort,
- Massive splenomegaly

27
Q

How is CML diagnosed?

A
  • Blood films and clinical features,
  • Molecular testing (FISH) to identify BCR-ABL mutation which can occur on a Philadelphia chromosome (if BCR-ABL negative then not CML)
  • Cytogenetic analysis (karyotyping)
28
Q

What is the treatment and complications in CML

A
  • CML is successfully treated with Imatinib (tyrosine kinase inhibitor)
  • So very few complications however can get imatinib resistance/intolerance or a blast crisis.
29
Q

What are the different phases of CML?

A
  • Chronic phase,
  • Accelerated phase,
  • Myeloid blast phase

Glasgow Phase 3 (148 decks)

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