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8. CP - Core Haematology > (43) Acute leukaemia > Flashcards

(43) Acute leukaemia Flashcards

1
Q

Acute leukaemia is the result of what?

A

Accumulation of early myeloid and lymphoid precursors in the bone marrow, blood and other tissues

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2
Q

Acute leukaemia probably occurs by what?

A

Somatic mutation in a single cell within a population of early progenitor cells

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3
Q

May a mutation causing acute leukaemia be de novo?

A

May arise de novo or be the terminal event of a pre-existing blood disorder

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4
Q

What are the 2 main subgroups of acute leukaemia?

A
  • acute myeloid leukaemia (AML)

- acute lymphoblastic leukaemia (ALL)

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5
Q

How is acute leukaemia classified?

A

Divided into 2 main subgroups (AML and ALL) and then further divided on morphological grounds into various subcategories

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6
Q

What are the immature cells found in acute leukaemia?

A

Blast cells (abnormal immature white blood cells)

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7
Q

What are the clinical features of acute leukaemia?

A

Features of bone marrow failure:

  • anaemia
  • infections
  • easy bruising and haemorrhage
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8
Q

How many acute leukaemia affect other organs?

A

Organ infiltration by leukaemia cells may occur eg. spleen, liver, meninges, testes and skin

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9
Q

What are the different diagnostic techniques in acute leukaemia?

A
  • morphology
  • cytochemistry
  • immunological makers
  • cytogenetics, FISH
  • molecular techniques (PCR)
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10
Q

What are the 2 types of classification for AML?

A

FAB classification (morphological)

WHO classification (risk adapted)

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11
Q

What is the new cornerstone of leukaemia diagnosis?

A

Monoclonal antibody determination of surface antigen expression

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12
Q

What technique allows rapid leukaemia diagnosis?

A

Immunofluorescence and particularly fluorescence activated cell sorting (FACS)

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13
Q

Which immunological markers are used in leukaemia diagnosis?

A
  • monoclonal antibody determination of surface antigen expression
  • fluorescence activated cells sorting (FACS)
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14
Q

How can cytogenetics help in leukaemia diagnosis?

A

Cytogenetic analysis may help to confirm the diagnosis and indicate subtype

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15
Q

Certain abnormalities correlate with prognosis in leukaemia. Give examples

A

t(8;21) and t(15;17) in AML = good

monosomy 7 in AML and t(9;22) in ALL = bad

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16
Q

What is the favourable risk group in AML? (cytogentic abnormalities)

A

t(15;17), t(8;21), inv(16)

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17
Q

What is the intermediate risk group in AML? (cytogentic abnormalities)

A

t(9;11)

+8, +21

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18
Q

What is the poor risk group in AML? (cytogenetic analysis)

A

t(6;9), inv(3)
del(5q)
-7, -5

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19
Q

What numeric change chromosomal abnormalities occur in ALL?

A
  • high hyperdiploidy (>50 chromosomes)
  • hyperdiploidy (47-50)
  • pseudodiploidy (46+ struc/no change)
  • hypodiploidy
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20
Q

What structural chromosomal abnormalities occur in ALL?

A 
Ph chromosome
t(1,19)
t(4,11)
t(11,14)
t(8,14)
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21
Q

How do the chromosome number changes in ALL affect prognosis?

A

high hyperdiploidy = favourable

hyperdiploidy = intermediate

pseudodiploidy = intermediate

hypodiploidy = poor

22
Q

How do the structural abnormalities in ALL affect prognosis?

A

Ph chromosome = very poor

t(1,19) = poor

t(4,11) = poor

t(11,14) = intermediate

t(8,14) = very poor

23
Q

What is the Philadelphia chromosome?

A

A specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly CML cells) - defective and unusually short because of reciprocal translocation of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1

24
Q

What type of translocation occurs in the philadelphia chromosome?

A

t(9;22) translocation

25
Q

What is the fusion protein that results from translocation of chromosome 9 and 22 material?

A

bcr-abl

26
Q

What function does the bcr-abl fusion protein have?

A

Has tyrosine kinase activity

27
Q

What is the importance of molecular abnormalities in acute leukaemia?

A

Chromosomal translocations cause molecular changes which may be important in aetiology and monitoring response to treatment and in developing treatment strategies

28
Q

What is the gene fusion product in t(8;21) translocation?

A

AML-ETO

29
Q

What is the gene fusion product in t(15;17) translocation?

A

PML-RARa

30
Q

PML-RARa explains what?

A

The response of acute promyelocytic leukaemia (APML-M3) to all trans retinoid acid (ATRA)

31
Q

Give 3 molecular mutations in AML that result in abnormal cell proliferation

A
  • FLT3 mutation
  • Ras mutation
  • c-KIT mutations
32
Q

Give 3 molecular mutations in AML that result in a block in differentiation

A
  • CBF AML t(8;21) and inv(16)
  • PML-RARa t(15;17)
  • MLL translocations (11q23)
33
Q

Give a molecular mutation in AML that results in tumour suppression

A

NPM1

34
Q

Why are molecular mutations that cause abnormal cell proliferation, blockage in differentiation and tumour suppression all related to AML?

A

As they all disrupt normal maturation and differentiation of white blood cells

35
Q

In AML patients with normal cytogenetics (de novo AML), mutations in NPM1 gives what prognosis?

A

Good prognosis

36
Q

In AML patients with normal cytogenetics (de novo AML), mutations in FLT3 gives what prognosis?

A

Bad prognosis

37
Q

How does relapse free and overall survival differ between NPM1 and FLT3?

A

relapse free = 61% vs 47%

overall survival = 57% vs 23%

38
Q

Briefly describe the significance of molecular markers in AML

A
  • identification of mutations allows monitoring of disease

- potential for developing targeted therapy to reduce need for conventional chemotherapy

39
Q

How does the complete remission (CR) rate vary depending on cytogenetic profile in AML?

A

t(15;17), t(8;21), inv(16) = 91%

normal, all others = 86%

complex -5, -7, 3q = 63%

40
Q

How does the 5-year overall survival (OS) vary depending on cytogenetic profile in AML?

A

t(15;17), t(8;21), inv(16) = 65%

normal, all others = 41%

complex -5, -7, 3q = 14%

41
Q

What are the poor prognostic factors in ALL?

A
  • increasing age (>10)
  • high WCC
  • male sex
  • certain cytogenetic abnormalities
  • poor response to treatment
  • T-ALL and null-ALL
42
Q

How is AML managed/treated?

A
  • induction treatment to obtain remission, then consolidation with further course of combination chemotherapy
  • consider bone marrow transplantation in younger patients (sibling or MUD)
43
Q

How is ALL managed/treated?

A
  • induction chemotherapy, intensive consolidation chemotherapy, prophylaxis of meningeal leukaemia and intrathecal methotrexate and cranial irradiation
  • maintenance chemotherapy, or bone marrow transplantation in ‘bad-risk’ patients
44
Q

What is the main complication of therapy for acute leukaemia?

A

Neutropenic sepsis

45
Q

All patients with acute leukaemia receiving intensive chemotherapy will become what?

A

They will become neutropenic for 10-21 days

46
Q

How is neutropenic fever defined?

A

Pyrexia in the presence of a neutrophil count of less than 1.0x10^9/l

Frequently the neutrophil count will fall to levels below 0.2 or be unrecordable

47
Q

What are neutropenic patients in danger of?

A

They are in grave danger of developing overwhelming gram negative or gram positive infection (neutropenic sepsis!)

48
Q

What is the cornerstone of management of neutropenic sepsis?

A

Immediate administration of broad spectrum IV antibiotics (often Tazocin and Gentamicin) given empirically before the results of cultures are available

49
Q

What preventative measures are taken in neutropenia to prevent neutropenic sepsis?

A
  • protective isolation
  • prophylactic antibiotics eg. levofloxacin
  • use of granulocyte colony stimulating factors
  • strict hand hygiene
50
Q

Give a summary of acute leukaemia and its diagnosis and treatment

A

A rapidly developing haematological malignancy whose clinical features are due to the impaired production of normal blood cells

Increasing understanding of the cytogenetic and molecular processes involved is aiding diagnosis and guiding treatment strategies

However, the cornerstone of therapy remains intensive chemotherapy that brings risks for the patient, notably, neutropenic sepsis

8. CP - Core Haematology (11 decks)

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