Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MD2 Haematology > Acute and Chronic Leukaemia > Flashcards

Acute and Chronic Leukaemia Flashcards

1
Q

Distinguish between acute and chronic leukaemia

A

Chronic: insidious onset, usually less agressive, cells usually more mature

Acute: acute onset, often more aggressive, characterised by presence of immature blast cells in bone marrow and blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How are the vast majority of leukaemias categorised?

A

Acute or chronic (based on clinical presentation and response to therapy)

Myeloid or lymphoid (based on stem cell of origin; immunophenotype and morphological appearance enable differentiation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List 7 common aetiologies of leukaemia. Which is the most common?

A

Unknown (most common)

Previous cytotoxic therapy

Exposure to ionising radiation

Chemical exposure

Infections

Genetics

Rare familial syndromes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In what cell populations does leukaemia arise?

A

Stem cell and progenitor cell populations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is leukaemia?

A

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream

I.e. circulating malignant cells of haematopoietic origin in the blood or bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the epidemiology of leukaemia

A

7th major cause of death in Victoria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How can myeloid and lymphoid leukaemias be differentiated?

A

Immunophenotype

Morphological appearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the most common myeloid neoplasms?

A

Acute myeloid leukaemia (AML)

Chronic myeloid leukaemia (CML)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the most common lymphoid leukaemias?

A

Acute lymphoblastic leukaemia: precursor B-cell lymphoblastic leukaemia/lymphoma (most common) and precursor T-cell lymphoblastic leukaemia/lymphoma

Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Give an example of an infection causing leukaemia

A

HTLV-1 causing adult T cell leukaemia lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Give an example of a genetic abnormality predisposing to leukaemia

A

Trisomy 21 prediposes to high risk AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give an example of a rare familial syndrome which predisposes to leukaemia

A

Fanconi anaemia (FA): 52% of patients develop AML or MDS by age 50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give an example of a chemical exposure which predisposes to leukaemia

A

Benzene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What blood abnormalities are typically seen in acute leukaemia and how do these correlate with the clinical presentation? What other symptoms/signs are seen? What features are less common?

A

Anaemia: lethargy, dyspnoea, pallor, pre-syncope or syncope

Neutropenia: fevers, rigors, infections

Thrombocytopaenia: bruising, bleeding (petechiae in the pharynx may be seen before they appear on the skin so look inside the mouth!)

Other symptoms/signs: B symptoms (fever, sweats, weight loss)

Less commonly: lymphadenopathy (unusual), hepatosplenomegaly and symptoms of hyperleucocytosis (occlusions of the microcirculation)

Gum hypertrophy may be seen in acute monoblastic leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What feature is occasionally seen on CXR in ALL?

A

Mediastinal mass (may result in SVC obstruction)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Ix for acute leukaemia

A

FBE and peripheral blood smear

Bone marrow biopsy

Immunophenotyping

Cytogenetics

Molecular studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the aim of Ix into a suspected leukaemia?

A

Determine type, prognosis and how best to monitor response to therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What abnormalities are seen on blood film in acute leukaemia?

A

Circulating malignant cells (the most immature of which are called blasts; often difficult to differentiate these from normal cells unless there are specific morphological features)

Abnormalities in multiple blood lineages typical, particularly cytopaenias as a result of suppression of normal haematopoiesis

Leukoerythroblastosis (causes leukoerythroblastic anaemia; anaemia due to “crowding out” of bone marrow)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What abnormalities are seen on bone marrow biopsy in acute leukaemia?

A

Blasts >20% of nucleated cells is diagnostic of an acute leukaemia

Suppression of normal haematopoietic function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Features on bone marrow biopsy in AML

A

Excess of immature blasts with prominent nucleoli, scant cytoplasm and coarse chromatin

Auer rods (due to alignment of eosinophilic granules; pathognomonic of AML)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Features on bone marrow biopsy in ALL

A

Excess of blasts, some demonstrating vacuoles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Difference between bone marrow aspirate and trephine biopsy

A

Aspiration (fast but does not represent all cells): semi-liquid bone marrow, which can be examined under a light microscope and analysed by flow cytometry, chromosome analysis or PCR

Trephine biopsy (slow processing): yields a narrow, cylindrically shaped solid piece of bone marrow, which is examined microscopically (sometimes with aid of immunohistochemistry) for cellularity and infiltrative processes (provides cells and stroma constitution)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why is flow cytometry used in the diagnosis of leukaemias?

A

Indicates lineage commitment (i.e. myeloid vs lymphoid), which is often very helpful when the morphology is difficult to interpret

Can be used to identify aberrant expression (seen in 80% of acute leukaemias) which can be useful as a marker for monitoring disease response to chemotherapy: e.g. AML blasts may express a lymphoid Ag which is not seen on normal non-leukaemic blasts, and vice-versa in ALL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How is flow cytometry (which makes use of immunophenotyping) interpreted?

A

By the intensity with which a fluorescence-conjugated Ab stains cell surface proteins (can be interpreted with knowledge of what markers are specific for what cell types)

I.e. if strong staining, then the cell surface protein is present

Result is usually provided as a graph

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Give 2 examples of myeloid markers seen on flow cytometry which are suggestive of AML

A

CD34

CD33

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Give 2 examples of monocytic markers seen on flow cytometry which are suggestive of AML

A

CD11

CD14

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How are patients with AML who have normal cytogenetics risk stratified using molecular testing?

A

Poor prognosis: FLT3 internal tandem duplication

Good prognosis: nucleophosmin 1 (NPM1) and CEBPA

28
Q

How does the cytogenetics of AML influence prognosis? Give specific examples

A

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

Intermediate (70% of patients): mostly normal cytogenetics (but mutations can be seen on molecular testing)

Poor: monosomy 7, multiple complex abnormalities, Ch 3 abnormalities

29
Q

What abnormal transcripts can be identified on molecular testing in AML and used to confirm cytogenetic findings and to monitor response to future therapy?

A

PML-RARa transcript in t(15;17) APML

AML1-ETO in t(8;21)

30
Q

What leukaemias does benzene exposure predispose to?

A

AML

Aplastic anaemia

MDS

ALL

CML

31
Q

What factors are considered when determining the prognosis for a patient with AML?

A

At Dx: cytogenetics, molecular findings

During therapy: flow cytometric evidence of residual disease, disapearance of previous cytogenetic abnormalities

32
Q

Describe 4 ways response to chemotherapy in acute leukaemia can be monitored, and what result constitutes “remission” for each test

A

Marrow aspirate and trephine: <5% = morphological remission

Cytogenetics: disappearance of any previous abnormalities = cytogenetic remission

Flow cytometry: no detection of cells with aberrant phenotype = remission

Molecular studies: no detectable transcript if a quanitifiable translocation (e.g. AML1-ETO in t(8;21)) - serial zero levels correspond with remission and likely cure but rising levels may impend relapse

33
Q

What care approach is used for fit patients with AML?

A

Induction chemotherapy with the “7+3” approach: high dose cytarabine (HiDAC) for 7 days with the addition of an anthracycline (e.g. idarubicin) for 3 days

Determination of response after marrow recovery (usually takes ~1/12) with bone marrow aspirate and trephine (BMAT)

If good response, consolidation cycles (to prevent recurrence; usually 2 in AML), with BMAT after each cycle to check disease status

Determination of need for allogeneic transplant (stem cell allograft is the only real curative therapy, others just put the patient in remission): based on age (eligibility usually <60 years) and prognostic features either at diagnosis (using cytogenetics and mutations) or during therapy (e.g. level of abnormal transcripts where applicable)

34
Q

APML is an example of good prognosis AML but can still cause death within 24-48 hrs if the diagnosis is missed. Why?

A

There is widespread DIC with low fibrinogen due to release of procoagulants from malignant promyelocytes

Therefore any patient suspected of having APML should have an urgent BMAT and commencement of treatment

35
Q

AEs of idarubicin

A

Cardiotoxic (always check cardiac status of patient before using)

36
Q

What care approach is used for fit patients with ALL?

A

Induction chemotherapy: multiple drugs (crucial one is L-asparagine; targeted immunochemotherapy is most effective), including intrathecal chemo prophylaxis due to higher risk of CNS relapse

NB Intensity of chemo is determined by age, but there is a move to use more intensive paediatric regimens in young adults aged 18-30 to improve outcomes

Determination of response after marrow recovery (takes ~1/12), particularly focussing on flow cytometric quantification of residual disease

If good response, consolidation cycles followed by repeat assessment around day 100

Determination of need for allogeneic transplant: based on age (eligibiliy usually <50 years) and prognostic features either at diagnosis (e.g. bad cytogenetics) or during therapy (e.g. level of abnormal transcripts at day 30 and 100)

In patients not receiving a stem cell allograft, maintenance chemo is indicated for 2 years

37
Q

What is the major feature of presentation with APML?

A

Bruising and bleeding

38
Q

What are the morphological characteristics of APML on blood smear?

A

Characteristic faggot cells containing many Auer rods

39
Q

What cytogenetic abnormality confirms the diagnosis of APML after a suggestive smear, and what is the significance of this mutation?

A

t(15;17)

Translocation of retinoic acid receptor alpha (RARa) on Ch 17 with promyelocytic leukaemia gene (PML) on Ch 15, resulting in the molecular fusion transcript PML-RARa

40
Q

Mx of APML

A

Correct coagulopathy with platelets, cryoprecipitate and fibrinogen concentrate as need

Specific therapy include all trans-retinoic acid (ATRA; induces promyelocyte differentiation) and arsenic (using both of these shows a high survival rate; APML is now probably the most curable leukaemia)

41
Q

Give an example of cytogenetics which confer good vs poor prognosis for ALL

A

Poor: hypoploidy, t(4;11)

Good: children with hyperdiploidy (>50 Ch)

42
Q

What is the prognosis of t(9;22) in ALL (i.e. Ph+ ALL)?

A

Traditionally terrible but appears to be better with TK inhibitor therapy

43
Q

What are the 3 stages of CML? In what stage do the majority of patients present and how do they present?

A

Chronic (majority present in this phase; often asymptomatic finding on blood examination or for another reason; may have symtoms from splenomegaly or feel vaguely unwell)

Accelerated

Blast

44
Q

What clinical features are seen in untreated chronic leukaemia which progresses to the accelerated or blast phase?

A

Anaemia, high WCC

Fevers

Increasing splenomegaly

45
Q

What is the median time period from the chronic to the blast phase in CML?

A

3-5 years

46
Q

What features are seen on blood film in CML?

A

Hyperleukocytosis with all stages of myeloid development (spectrum of early myeloid cells, basophils, eosinophilia)

47
Q

Ix and expected results in CML

A

FBE: leukocytosis with spectrum of early myeloid cells, basophils, eosinophilia

Bone marrow (no longer a necessary test): extremely hypercellular, increased numbers of blasts in more advanced cases

Cytogenetics: Ph Ch t(9;22) is pathognomonic (can perform FISH to demonstrate; a positive FISH is diagnostic)

Molecular: BCR-ABL fusion gene (which has independent TK activity)

48
Q

How was CML treated pre-2000?

A

Managed with toxic, non-specific therapy (e.g. IFN, hydroxyurea) to prevent progression to blast crisis

Definitive therapy was allogenic bone marrow transplant for patients <50-60

49
Q

Current standard therapy for CML

What are the benefits of this treatment?

A

TK inhibitors (first was imatinib)

Benefits: selective killing of CML cells, virtually eliminated need for allograft, no major toxicity in most patients

It is expected that patients treated with TK inhibitors will have a normal lifespan unless tolerance generates (even then, there are 2nd and 3rd gen drugs now so this may not be a problem for most patients)

50
Q

Mechanism of action of imatinib

A

Blocks ATP binding of BCR-ABL protein, and reduces signalling that drives cell proliferation

51
Q

How is response to therapy monitored in CML?

A

Previously: regular BMAT looking at % of Ph+ metaphases (where a complete cytogenic response, CCR, was defined as 0% Ph+)

Now: monitor by PCR the amount of abnormal BCR-ABL transcript in peripheral blood every 3/12s (aim is at least a major molecular response, MMR, which is defined as <1% Ph+; a rise in BCR-ABL % may signify resistance to therapy, most often due to a mutation in the binding site of imatinib to ABL)

52
Q

What options are available for CML patients who develop resistance to imatinib?

A

2nd gen TK inhibitors (which are more potent in vitro than imatinib) have been successful in patients losing response to imatinib

The two available are dasatinib and nilotinib

53
Q

What is the best current available therapy for CML as suggested by the literature?

A

Newer TK inhibitors (dasatinib, nilotinib) as part of initial therapy; show a superior molecular response within 24/12 of FU and were approved under PBS in 2012 for upfront therapy

54
Q

What is the most common leukaemia?

A

CLL

55
Q

How does CLL present?

A

May be asymptomatic finding on blood film

Advanced cases may present with:

Lymphadenopathy, splenomegaly

B symptoms

Cytopaenia due to marrow infiltration

Hypogammaglobulinaemia and recurrent infection

Immune complications (AI haemolytic anaemia, AIHA, and ITP)

56
Q

What morphological findings are seen on blood smear and BMAT in CLL?

A

Small mature lymphocytosis with smear cells

Cytopaenias due to AI phenomenon or marrow infiltration

57
Q

What immunophenotype is seen in CLL?

A

B lymphocytes co-expressing CD5 (they don’t normally) and CD19, CD23

58
Q

How can staging of CLL and monitoring of response to therapy be achieved?

A

Staging and monitoring achieved by by looking at degree of nodal involvement on CT (but not useful in asymptomatic patients)

59
Q

What cytogenetic abnormalities are associated with an indolent vs more aggressive course of CLL? How can these be detected?

A

Indolent: deletion 13q

Aggressive: deletion 17p (with loss of tumour suppressor gene p53)

Use FISH as it may detect abnormalities not detectable using standard techniques

60
Q

Ix for CLL and reasons for each Ix (e.g. diagnosis, staging, monitoring, etc)

A

Flow cytometry for Dx

BMAT and cytogenetics often not necessary (may do in younger patients for prognostic significance)

CT scans for staging and monitoring (not useful in asymptomatic patients)

61
Q

What criteria are used to determine who needs treatment for CLL and why?

A

Based on symptoms, cytopaenia, bulky glands or spleen, etc, NOT on level of WCC

Pre-emptive chemotherapy in patients with no symptoms is of no benefit; for early stage disease, a “watch and wait” approach is indicated

62
Q

Describe the natural Hx of CLL

A

Many patients (esp with minimally raised WCC) follow an indolent clinical course with prolonged survival even without treatment

A subset of patients (esp those with loss of p53) progress to terminal phase more rapidly

63
Q

Mx of CLL

A

Early stage disease with no clinical manifestations: expectant Mx only, no benefit from therapy

Symptomatic patients: chemoimmunotherapy is mainstay for young fit patients (fludarabine + cyclophosphamide + rituximab, FCR, is currently the best regimen)

For relapsed disease: consider other monoclonal Abs (e.g. alemtuzumab)

Allograft is only curative option but majority of patients are ineligible

64
Q

Give an example of an erythroid marker on flow cytometry

A

GlyA

65
Q

What is the role of cytogenetics in leukaemia?

A

Assists with:

Dx

Disease classification and monitoring

Treatment decisions

Prognosis

66
Q

What cytogenetic abnormality is seen in APML?

A

t(15;17)

MD2 Haematology (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions