Introduction to Leukaemias Flashcards Preview

Sem 4: TI2 > Introduction to Leukaemias > Flashcards

Flashcards in Introduction to Leukaemias Deck (22):
1

What are the 4 basic leukaemia classifications?

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

2

What is the differentiation between acute and chronic leukaemias?

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

3

Give 2 examples of hybrid oncogenes that cause leukaemias. 

  • BCR-ABL - in CML. 
  • PML-RARA - in AML M4.

4

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

HTVL-1

5

Name 2 rare genetic diseases that predispose to leukaemia. 

  • Fanconi's anaemia
  • Down's syndrome

6

Outline the treatment options used in leukaemias. 

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

7

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

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

8

Outline the side effects of chemotherapy. 

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

9

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

  • 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. 

10

What are the disadvantages of SCBMT in treatment of leukaemia?

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

11

Outline the signs and symptoms of acute leukaemias. 

  • 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.

12

Describe how acute leukaemias are diagnosed. 

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

13

Outline the pathophysiology of acute leukaemias. 

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

14

Outline the signs and symptoms of chronic lymphocytic leukaemia. 

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

15

Outline the outcomes of acute and chronic leukaemias. 

  • 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. 

16

Outline the signs and symptoms of chronic myeloid leukaemia. 

  • Anaemia
  • Night fever/sweats
  • Splenomegaly

17

Describe how chronic myeloid leukaemia is diagnosed. 

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

18

How is chronic myeloid leukaemia treated?

  • 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

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

  • 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

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

  • 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

How is the response to treatment monitored in CML patients?

  • 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

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

  • 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