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Cancer Care > Leukaemia > Flashcards

Leukaemia Flashcards

1
Q

What are the main types of leukaemia?

A

Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphoid leukaemia

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2
Q

What is the pathophysiology of ALL?

A

Arises from lymphoid progenitor cells that undergo malignant transformation

Most are B cell in origin
May arise from T cells

As clonal expansion occurs, these precursors replace other haematopoietic cells in the bone marrow

Classified as B cell lineage
T cell lineage

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3
Q

What cytogenic features are seen in ALL?

A

t(12;21) most common translocation seen in children - TEL-AML fusion gene

t(9;22) Philadelphia chromosome - BCR-ABL

t(4;11) in infants <12 months, rare in adults

Hyperdiploid karyotype
Hypodiploid karyotype

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4
Q

What are the clinical features of ALL?

A

Marrow suppression symptoms and lymphadenopathy

Marrow failure:
Anaemia - fatigue, SOB, angina
Neutropenia - recurrent infections
Thrombocytopenia - petechiae, nose bleeds, bruising

Tissue infiltration
Lymphadenopathy
Hepatosplenomegaly
Bone pain
Mediastinal mass - may result in SVCO
Testicular enlargement

Leucostasis
May occur due to large numbers of WCs entering blood stream
Organ dysfunction due to impairment through small vessels

Altered mental state, headache, SOB, visual changes

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5
Q

What is the presentation of T cell ALL?

A

Rarer than B cell form
Typically present in adolescent males
With lymphadenopathy or a mediastinal mass

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6
Q

What are the investigations for ALL?

A

Bloods
FBC, U&Es, LFTs, clotting
DDIMER, bone profile,
uric acid, LDH, BBV

Most will present with pancytopenia

Uric acid and LDH non specific markers of tumour border

DDIMER and coag for DIC

Imaging
CXR - mediastinal mass
CT chest, abdo pelvis for lympadenopathy and organ involvement
CT/MRI head exclude differentials, neurology

Bone marrow aspiration and biopsy, staining and review of cell morphology
Immunophenotyping

Blood smear
Pleural tap if pleural effusion
LP if CNS involvement

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7
Q

What are high-risk factors for adult patients, indicating a poorer prognosis?

A 
Age - worse with advancing age
Performance status > 1
WCC - >30 for B, >100 for T
Cytogenetics - 9;22, 4;11
Immunophenotype - proB, early and mature T
CNS involvement
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8
Q

What is the management of ALL?

A

Referral to haemato-oncology specialists

  1. Pre-phase therapy - steroids, with allopurinol and IV hydration, reduces risk of TLS

Can give rasburicase to prevent TLS as helps clears uric acid from body

Leucopheresis can help reduce WCC for TLS.
Anaemia and thrombocytopenia may need treatment, G-CSF for neutropenia.

  1. Induction chemotherapy
    For complete remission or molecular complete:
    Complete - not in bone marrow, peripheral blood or CSF
    MolecularCR - minimal disease not detectable by sensitive molecular probe
  2. Maintenance therapy
    Daily 6-mercaptopurine
    Weekly methotrexate
    Reduce risk of recurrence
  3. Stem cell transplant
    Allogenic
    Myeloablative transplant = high dose chemo, then stem cell transplant
  4. Palliative care
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9
Q

What complications are ALL patients at risk of?

A

TLS
Neutropenic sepsis
SVCO - dyspnoea, facial swelling, cough secondary to mediastinal mass
Chemo side effects - early mucositis, nausea, vomiting, hair loss or late - cardiomyopathy, secondary malignancies

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10
Q

What do you look for in a cytochemical stain in acute leukaemias?

A

TdT+ in lymphoblasts - ALL

Myeloperoxidase in myeloblasts - AML

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11
Q

How is philadelphia + ALL managed?

A

Stem cell transplant

Imatinib

TKI’s - tyrosine kinase inhibitors

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12
Q

What is APL? What genetics is it associated with?

A

Acute Promyelocytic Leukaemia

translocation of chromosome 15 and 17 t(15;17)

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13
Q

How does APL normally present? Describe the pathophysiology of this

A

Younger than AML and it’s other subtypes (age 25 ish)

build up of promyelocytes –> lots of Auer rods –> high coagulation risk –> DIC

Medical Emergency!

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14
Q

How is APL treated?

A

It responds to retinoic acid (ATRA)

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15
Q

What is myelodysplastic syndrome?
What would the bone marrow look like?
How would it present?

A

Condition which is a precursor of AML

Blasts build up in marrow but <20%

Same signs - cytopaenia, bruising etc.

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16
Q

Describe the age presentation of ALL vs AML

A

ALL is childhood (2-5)

AML is adults (65)

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17
Q

What are the blood results in ALL?

A

normocytic, normochromic anaemia
thrombocytopenia
leukocytosis but with neutropenia
reduced reticulocytes

Renal failure: raised K and phosphate

raised LDH

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18
Q

What is the bone marrow like in ALL?

A

hypercellular

blast cell infiltration

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19
Q

On cytochemical staining, what is seen in ALL? Compare this to AML?

A

blasts are TDT+ve

In AML it is myeloperoxidase +ve

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20
Q

What is ALL associated with?

A

Most common in children

Associated with Down’s

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21
Q

What is CLL associated with?

A

Most common leukaemia in adults overall
Associated with warm haemolytic anaemia
Richter’s transformation in lymphoma
Smudge/smear cells

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22
Q

What is CML associated with?

A

Has three phases
A 5 year - ‘asymptomatic chronic phase’
Associated with the Philadelphia chromosome

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23
Q

What is AML associated with?

A

Most common adult acute leukaemia
Can be the result of a transformation from a myeloproliferative disorder
Associated with Auer rods

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24
Q

What are the differentials for petechiae?

A 
Leukaemia
Meningococcal sepsis
Vasculitis
Henoch Schonlein Purpura
Idiopathic Thrombocytopenia Purpura 
Non accidental injury
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25
Q

What is the pathogenesis of a haematological malignancy?

A

Cause - environment, toxin, virus infection, drug, genetic predisposition: translocation, deletion, duplication, point mutation

Pathogenesis - altered gene expression, change in oncogene or tumour suppressor gene

Leads to decrease in apoptosis and differentiation, and proliferation increase

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26
Q

What are lymphoid haematological malignancies?

A

Acute - lymphoblastic leukaemia

Chronic
Lymphocytic leukaemia
Non-Hodgkin lymphoma
Hodgkin lymphoma
Multiple myeloma
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27
Q

What are myeloid malignancies?

A

Acute myeloid leukaemia

Chronic myeloid leukaemia
Myelodysplasia
Myeloproliferative disorders e.g. polycythaemia vera, essential thrombocytopenia, primary myelofibrosis

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28
Q

What would be shown on a blood film in T-ALL?

A

Bone marrow showing large number of lymphoblasts with a high nuclear/cytoplasmic ratio

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29
Q

What would be shown on a blood film in B-ALL?

A

Large blasts with characteristic vacuoles and blue cytoplasm

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30
Q

What are prognostic indicators in AML suggesting a better outcome?

A

Cytogenic changes - 8;21, 15;17, inversion 16

Remission after one course of chemotherapy

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31
Q

What indicates poor risk in AML?

A

Cytogenic changes - monosomy 5, monosomy 7, complex charyotypes, 11q23 abnormalities
Aged over 70

32
Q

How can AML be classed?

A

Primary or secondary; as may follow a previous myeloproliferative or myelodysplastic event

33
Q

What is the aetiology of AML?

A

Not completely understood
Myelodysplastic syndrome and high risk features e.g. excessive blasts
Congenital disorders e.g. Down’s, Fanconi anaemia
Radiation exposure
Prev chemo
Toxins - bezene, organochloride insecticides

34
Q

What are the clinical features of AML?

A

Pancytopenia
Fatigue, SOB, angina, recurrent infections, petechiae, nosebleeds

Tissue infiltration
Leucostasis

35
Q

What are the investigations for AML?

A

Normocytic normochromic anaemia is common
As is thrombocytopenia and reduced reticulocyte count

Usual blood panel
Clotting and DDIMER - DIC
Bone profile, Mg

Blood smear:
Auer roads - azurophilic structures seen in myeloid blasts (also seen in myelodysplastic syndrome)

Bone marrow aspirate
Myeloid blast count of >20%

LP if concern of CNS involvement

36
Q

What is the management of AML?

A

Education and support
Cytoreduction considered in signs of leukostasis and WBC count >100 with hydroxycarbamide
Intrathecal chemo - cytarabine if CNS involved
TLS - prophylaxis where indicated

Chemo:
Induction - cytarabine, daunorubicin and gemtuzumab
Consolidation - IDAC

Allogenic haematopoietic stem cell transplant following myeloablative conditioning regimes +- total body irradiation

37
Q

What factors indicate poorer prognosis in AML?

A

‘Secondary leukaemia’ following a preceding haematological disorder e.g. MDS

Age >60
Poor performance status
Multiple significant co-morbidities
Prev haematological disorders, dysplasia
Prev exposure to chemo/radio
Certain disease subtypes
38
Q

What are the phases of treatment for leukaemia?

A

First phase remission induction with high dose intensive combination chemo
to re-establish normal haemopoiesis
Then post induction chemo initially intensive

Then for ALL less intensive maintenance chemo

Requires 4-6 weeks in hospital

39
Q

What is chronic lymphocytic leukaemia?

A

Lymphoproliferative disorder of B lymphocytes
Results from abnormal clonal expansion of B cells
Leads to widespread lymphadenopathy

Due to genetic alterations and changes to the bone marrow microenvironment

40
Q

What genetic alterations are associated with CLL?

A 
TP53 mutation, major tumour suppressor gene
11q and 13q14 deletions
Trisomy 12
Overexpression of BC12 proto-oncogene 
NOTCH1 mutation
41
Q

What is monoclonal B cell lymphocytosis?

A

Premalignant disorder
Genetic alterations allow the formation of a clone of B lymphocytes

Overtime further mutations and bone marrow microenvironment changes allows progression to CLL

42
Q

What are the clinical features of CLL?

A

Hallmark feature is lymphadenopathy
due to infiltration of malignant B lymphocytes

Large proportion may be asymptomatic so detected on routine blood tests or finding of abnormally enlarged but painless lymph nodes

Weight loss, anorexia
Fevers, night sweats
Lethargy

Lymphadenopathy, most commonly cervical, supraclavicular, axillary
Hepatomegaly
Splenomegaly

43
Q

What features occur in association with complications of CLL?

A

Autoimmune haemolytic anaemia - pallor, SOB, weakness, dizziness

Immune thrombocytopenia - petechiae, bruising, mucosal bleeding

Hypogammaglobulinaemia - recurrent infections, organ specific

44
Q

How can a diagnosis of CLL be made?

A

Excess lymphocytes found to be clonal (of same type)
Assessed by flow cytometry

Absolute B lymphocyte count of >5x10^9 for > 3 months or >1 cytopenia due to bone marrow infiltration

And characteristic immunophenotype features and presence of disease manifestations

45
Q

What is done for investigations for CLL?

A

Clinical examination to determine presence or absence of lymph node involvement inc specific sites, splenomegaly and hepatomegaly

Bloods - FBC, routine biochemistry, blood film, haemolysis screen, immunoglobulins

Cytogenetics and immunophenotyping

Blood film
Lymphocytes, smudge cells

Bone marrow assessment not usually required unless alternative diagnosis

CT imaging if concerned about lymphomatous transformation
CXR

Lymph node biopsy
Virology

46
Q

What is the staging of CLL?

A

Binet Staging
Based on number of lymphoid sites affected on clinical examination

Stage A < 3 sites
Stage B >3 lymphoid sites
Stage C - presence of anaemia or thrombocytopenia

An area is counted as one regardless of whether unilateral or bilateral

Rai Staging
Based on expected natural progression to marrow failure

Stage 0 - lymphocytosis
Stage I-II lymphocytosis, lymphadenopathy, organomegaly
Stage III-IV lymphocytosis, anaemia, thrombocytopenia, lymphadenopathy, organomegaly

47
Q

What are some prognostic factors for CLL?

A

Lymphocyte doubling time
Genetic abnormalities e.g. TP53, trisomy 12
Beta 2 microglobulin
Mutated immunoglobulin heavy chain variable genes

48
Q

What is the management for CLL?

A

Watch and wait if asymptomatic indolent
Assessment and FBC at 3 monthly intervals

Front line therapy with no TP53 mutations - Fludarabine, cyclophosphamide, Rituximab

Front line therapy with mutations Ibrutinib, Rituximab

Chemo - e.g. chlorambucil

Small molecule inhibitors e.g. venetoclax, Ibrutinib

Monoclonal antibodies e.g. Rituximab

Corticosteroids

Allogenic stem cell transplantation

Supportive care - vaccination, abx, intravenous immunoglobulins, PJP and herpes zoster prophylaxis

49
Q

What is Richter transformation?

A

CLL becomes a form of aggressive lymphoma

Associated with rapid deterioration

50
Q

What are some of the complications of CLL?

A

May transform into another lymphoproliferative disorder

Prolymphocytic leukaemia
Hodgkin lymphoma
Multiple myeloma

Secondary infections - herpes, PJP, bacterial
Autoimmune complications
Hyperviscosity syndrome
Secondary malignancies

51
Q

What are the indications for treatment of CLL?

A

Bone marrow failure - Hb <100, plts <100 x 10^9 g/L
Massive, progressive or symptomatic splenomegaly
Massive progressive or symptomatic lymphadenopathy
Progressive lymphocytosis
Autoimmune complications not responsive to steroids
Symptomatic/functional extra nodal sites
Disease related symptoms

52
Q

What disease related symptoms should you be on the look out for, for CLL?

A

Significant weight loss
Severe fatigue
>2 weeks of fever
>1 month of night sweats, without infection

53
Q

What is chronic myeloid leukaemia associated with?

A

Philadelphia chromosome - translocation of 9 and 22

Results in a constitutively activated tyrosine kinase

54
Q

What are the clinical features of CML?

A

Some asymptomatic, or non vague features, picked up on other tests

Fatigue, weight loss
Night sweats, anaemia
SOB, angina

Thrombocytopenia - petechiae, nose bleeds, bruising

Splenomegaly - early satiety, abdominal pain

Bone pain

Leucostasis - headache, breathlessness, visual changes, priapism

Splenomegaly
Hepatomegaly
Lymphadenopathy
Leucostasis - altered mental state, priapism

55
Q

What are the investigations for CML?

A

Bloods - excessive granulocytosis with typical left shift

Bloods
FBC - raised WCC
Blood film - immature and mature myeloid cells

LDH, urate and potassium useful markers of disease
Renal function, LFTs, bone profile, Mg, lipids, HbA1c

Cytogenetics, FISH to identify Ph chromosome - BCR-ABL1 fusion

Bone marrow aspirate
Marrow is hyper cellular with myeloid hyperplasia

56
Q

Why is allopurinol given in chemo treatments?

A

Reduce level of uric acid and risk of tumour lysis syndrome

57
Q

What are the disease phases of CML?

A 
1. Chronic phase
Most present at this point
Features non-specific
Fatigue, weight loss, NSs
Prior to advance tx, this phase would last 3-5 years
  1. Accelerated phase
    Features more apparent and severe, harder to treat
    Lasts 6-18 months untreated

Blasts in blood or marrow15-29%, basophils in blood
Persistent thrombocytopenia
Clonal chromosome abnormalities in Ph cells

3. Blast crisis
Resembles an acute leukaemia
Without tx, survival is a few months
Blasts in blood or bone marrow >30%
Extramedullary blast proliferation
58
Q

What is the management of CML?

A

Tyrosine kinase inhibitors - block the enzyme created by BCR-ABL1 fusion gene

Invasive chemo reserved for patients with plastic transformation

Allogenic stem cell transplant for chronic patients

59
Q

What tyrosine kinase inhibitors are used in the treatment of CML?

A

Imatinib
Dasatinib
Nilotinib

60
Q

What are some side effects of tyrosine kinase inhibitors used in CML?

A 
Nausea, vomiting
Oedema, cramps, rashes
GI symptoms, headache
Fatigue
Derangement of LFTs
Pleuro-pulmonary toxicity
61
Q

What are the phases of CML?

A

Chronic phase
May need emergency cytoreduction if WCC v high
Good oral hydration and allopurinol to reduce risk of TLS, use of TKIs

Advanced phase
May have undergone blastic transformation
Second generation TKI with or without intensive chemo

62
Q

What are the complications of CML?

A

Thrombotic event

Blast transformation to an acute leukaemia

63
Q

What cytogenetic findings suggest CML?

A

Philadelphia!! Seen in 95% of patients with CML

64
Q

What is seen on a blood film of CML? and what is seen in the bone marrow?

A

Granulocytes at all different stages of development

BM: hypercellular with ++ granulocytes

65
Q

Blood results seen in CML?

A

+++ leukocytosis
normocytic, normochromic anaemia
Thrombocytosis progresses to penia

66
Q

What is Richter transformation? What is the pathophysiology? How does it present?

A

Transformation of CLL to a high grade lymphoma
Due to leukaemia cells infiltrating the lymph node

SUDDEN deterioration of symptoms

  • B symptoms
  • lymph node swelling
  • abdo pain and nausea
67
Q

What is hypogammaglobulinaemia and what does it lead to?

A

It results in a lack of antibodies and therefore infections

68
Q

What is seen on a blood film in CLL?

A

Smudge/smear cells
Lymphocytosis
NOT blasts

69
Q

Poor prognostic features of AML?

A

> 60
20% blasts after first chemo
chromosome deletions

70
Q

Characteristics of the bone marrow in AML?

A

Hypercellular

>20% Blast cells

71
Q

What is seen on the blood film of AML?

A

Blast cells with Auer rods

72
Q

What is myelodysplastic syndrome?
What would the bone marrow look like?
How would it present?

A

Condition which is a precursor of AML

Blasts build up in marrow but <20%

Same signs - cytopaenia, bruising etc.

73
Q

When are most CML’s diagnosed?

A

in the chronic phase - incidentally found on routine bloods

74
Q

What is a blast crisis?

A

No ability to differentiate so resemble acute leukaemia

Bone marrow exhaustion and large tumour burden - systemically unwell and rapidly fatal

75
Q

What is regularly monitored throughout management of CML?

A

FISH studies - show % bone marrow cells Ph+

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