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Sem 4: TI2 > Introduction to Leukaemias > Flashcards

Introduction to Leukaemias Flashcards

1
Q

What are the 4 basic leukaemia classifications?

A
  • Acute myeloid (myeloblastic) leukaemia =
  • Chronic myeloid (granulocytic) leukaemia
  • Acute lymphoid (lymphoblastic) leukaemia
  • Chronic lymphoid (lymphocytic) leukaemia
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2
Q

What is the differentiation between acute and chronic leukaemias?

A
  • Acute - undifferentiated leukaemias characterised by immature WBC - i.e. blast cells.
  • Chronic - differentiated leukaemias characterised by mature WBC.
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3
Q

Give 2 examples of hybrid oncogenes that cause leukaemias.

A
  • BCR-ABL - in CML.
  • PML-RARA - in AML M4.
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4
Q

Which virus is a predisposing factor to adult T-cell leukaemia?

A

HTVL-1

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5
Q

Name 2 rare genetic diseases that predispose to leukaemia.

A
  • Fanconi’s anaemia
  • Down’s syndrome
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6
Q

Outline the treatment options used in leukaemias.

A
  • Chemotherapy - cytotoxic drugs
  • Stem cell and bone marrow transplant (SCBMT)
  • Disease specific agents - including oncogene targeted drugs
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7
Q

Name 2 examples of chemotherapy drugs used in leukaemia and describe their mechanisms of ation.

A

Cytosine arabinoside:

  • Cytosine analogue
  • Interferes with deoxynucleotide synthesis
  • Prevents successful DNA replication

Vincristine:

  • Binds to tubulin dimers
  • Inhibits microtubule formation
  • This prevents mitotic spindle formation
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8
Q

Outline the side effects of chemotherapy.

A
  • Cytotoxic drugs kill normally dividing cells.
  • GI epithelium - nausea and diarrhoea.
  • Hair follicles - hair loss.
  • Loss of fertility.
  • Haematopoeitic progenitors - bone marrow suppression.
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9
Q

Explain how stem cell and bone marrow transplant (SCBMT) is used to treat leukaemia.

A
  • Give intense chemotherapy and total body irradiation.
  • Wipes out leukaemic cells and normal stem cells.
  • Reconstitute bone marrow with transplanted stem cells.
  • Transplanted cells may attack leukaemic cells - “graft vs leukaemia” effect.
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10
Q

What are the disadvantages of SCBMT in treatment of leukaemia?

A
  • Shortage of HLA matched donors.
  • High mortality of procedure in older and sicker patients.
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11
Q

Outline the signs and symptoms of acute leukaemias.

A
  • Typical symptoms due to bone marrow suppression.
  • Thrombocytopenia - leads to purpura (bruising), epistaxis (nosebleed), bleeding gums.
  • Neutropenia - recurrent infections.
  • Anaemia - lassitude, weakness, shortness of breath.
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12
Q

Describe how acute leukaemias are diagnosed.

A
  • Peripheral blood - blast cells, cytopenias.
  • Bone marrow aspirate - > 30% blasts is diagnostic of acute leukaemia.
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13
Q

Outline the pathophysiology of acute leukaemias.

A
  • Blast cells - maturation arrest.
  • Blast cell pool is very large.
  • Cell death halted due to undifferentiated blasts.
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14
Q

Outline the signs and symptoms of chronic lymphocytic leukaemia.

A
  • Thrombocytopenia
  • Anaemia
  • Recurrent infections - neutropenia and suppressed lymphocyte function
  • Lymph node enlargement
  • Hepatosplenomegaly
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15
Q

Outline the outcomes of acute and chronic leukaemias.

A
  • ALL - 90% childhood cases long-term remission/cure, adult cases have poorer prognosis - due to different cell of origin and different oncogene mutations.
  • AML - > 80% long-term remission in young adults with aggressive treatment, elderly unable to tolerate aggressive chemotherapy or SCBMT.
  • CLL - mainly seen in elderly, controlled by regular chemotherapy - most survive > 2 years and many > 12 years.
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16
Q

Outline the signs and symptoms of chronic myeloid leukaemia.

A
  • Anaemia
  • Night fever/sweats
  • Splenomegaly
17
Q

Describe how chronic myeloid leukaemia is diagnosed.

A
  • Neutrophilia - very high WBC count
  • Left shift in blood and bone marrow.
  • Presence of Philadelphia chromosome - BCR-ABL translocation.
18
Q

How is chronic myeloid leukaemia treated?

A
  • Imatinib - first line drug - tyrosine kinase inhibitor - specific to BCR-ABL.
  • Survival on treatment measured in years.
  • Progresses to accelerated phase and blast crisis.
  • Blast crisis resembles acute leukaemia and is hard to treat.
  • Allogeneic bone marrow or stem cell transplant curative.
  • Autologous transplant sometimes tried.
  • Most patients > 50 years old, don’t tolerate transplant.
19
Q

What is the Philadelphia chromosome and what is its clinical significance?

A
  • Philadelphia chromosome (Ph’) = 22q- = shorter than normal short arm of chromosome 22.
  • Balanced reciprocal translocation of chromosome 22 to chromosome 9: t(9;22) - resulting in 9q+.
  • Translocation leads to hybrid BCR-ABL oncogene - BCR fragment from Chr22, ABL on Chr9.
  • 95% of CML cases have detectable Ph’ chromosome.
  • Of remaining 5% some have BCR-ABL gene, some have a different disease requiring distinct therapy.
20
Q

Describe in detail the pathophysiology of CML and the Philadelphia chromosome.

A
  • ABL previously known to be an oncogene.
  • ABL protein is a tyrosine kinase - tightly regulated.
  • BCR-ABL hybrid leads to constitutive activity of tyrosine kinase - i.e. unregulated.
  • Causes proliferation of progenitor cells in the absence of growth factors.
  • Decreased apoptosis.
  • Decreased adhesion to bone marrow stroma.
21
Q

How is the response to treatment monitored in CML patients?

A
  • Reverse transcription-PCR.
  • BCR-ABL mRNA converted to ds cDNA by reverse transcriptase.
  • PCR with BCR and ABL specific primers.
  • Only get products if BCR and ABL on same molecule.
  • Quantification of PCR products indicates the extent of residual disease.
22
Q

Explain why imatinib is the first line treatment for CML and describe its limitations.

A
  • Remission induced in more patients
  • Greater durability
  • Fewer side effects
  • A proportion of patients are effectively cured - but monitored for relapse by RT-PCR
  • However, some patients become drug resistant

Sem 4: TI2 (19 decks)

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