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Haematology > Leukaemia > Flashcards

Leukaemia Flashcards

1
Q

Acute leukaemia is the accumulation of …% blasts in the bone marrow

A

> 20%

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2
Q

Can you guess the type of leukaemia by age?
Newborn - 14yo = ?
40-60yo = ?
>60 yo = ?

A

ALL
AML or CML
CLL

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3
Q

Is AML an oligoclonal or polyclonal disease at diagnosis?

A

Oligoclonal

AML is an oligoclonal disease at diagnosis e.g. has 5 mutations only –> chemotherapy –> successful at eliminating one of the clones but ineffective at eliminating other clones –> these other clones become the site of relapse–> further mutate and acquired other mutations –> chemo resistance

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4
Q

What would you expect to see on blood film in AML?

A

Large blast type cells. Myeloblasts are characterised by Auer rods

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5
Q

How do you diagnose AML?

A

Bone marrow biopsy

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6
Q

Why is it important to recognise acute promyelocytic leukaemia (APML)?

A

MEDICAL EMERGENCY
Need transfer to site where treatment can be initiated within hours
Rapidly fatal subtype of AML with severe bleeding complications related to DIC (present with thrombocytopenia associated with bone marrow failure, prolonged coagulation, hyperfibriginemia)

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7
Q

What is the genetic translocation involved in acute promyelocytic leukaemia?

A

t(15;17) which involves translocation of the retinoid acid receptor (RAR) on chromosome 17 to chromosome 15. RAR disruption blocks maturation and promyelocytes (blasts) accumulate.

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8
Q

How do you diagnose acute promyelocytic leukaemia?

A

Rapid diagnosis with PML-RARA PCR or FISH karyotype demonstrates t(15;17)

Commence treatment in suspected APML, before FISH results come back (take 24h)

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9
Q

How do you treat acute promyelocytic leukaemia?

A

All-trans-retinoic acid (ATRA; vitamin A derivative)
Arsenic
+/- chemotherapy

Urgent control of DIC - platelet transfusion and fibrinogen replacement

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10
Q

What is differentiation syndrome (in the treatment of acute promyelocytic leukaemia)?

A

Cell differentiation induced by ATRA leads to rising WCC and cytokine release

  • Leaky capillaries
  • Respiratory distress
  • Fluid overload

Prevention: steroids and chemo

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11
Q

How do you treat differentiation syndrome (in the treatment of acute promyelocytic leukaemia)?

A

Rx: dexamethasone and consider delaying chemotherapy

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12
Q

Name 3 subtypes of AML

A

Acute promyelocytic leukaemia
Acute monocytic leukaemia
Acute megakaryoblastic leukaemia

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13
Q

How do you treat a young person with AML?

A

7+3 = cytarabine for 7d + anthracycline for 3d
This is intense therapy and people are aplastic for 2 weeks

Supportive care for BM failure
§ Transfusion support
§ Infection prophylaxis (Posaconazole to prevent fungal infection)
§ Nutrition support for nausea and LOA
§ Psychological support – people are in hospital for long periods
§ Management of bleeding
§ Management of febrile neutropenia

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14
Q

Why is it important to test for FLT3 mutation?

A

Common mutation in AML
Measured by rapid PCR test
Important to identify as you add midostaurin to standard chemotherapy

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15
Q

How do you treat an old/unfit individual with AML?

A

Palliative treatments

Low dose chemotherapy - cytarabine OR azacitidine OR venetocloax + cytarabine (best but not PBS)

Supportive care - blood transfusions, abs

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16
Q

What happens in the bone marrow in myelodysplastic syndrome?

A

Ineffective haematopoiesis in the bone marrow where immature blood cells do not mature to become healthy blood cells

Hypercellular bone marrow

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17
Q

What is myelodysplastic syndrome associated with?

A

Radiation or chemotherapy exposure but is more commonly a primary process

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18
Q

Is MDS always severe?

A

Ranges in severity from asymptomatic disease characterised by mild normocytic or macrocytic anaemia to a transfusion dependent anaemia heralding conversion to AML

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19
Q

MDS can transform to …

A

AML

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20
Q

Whats 5q minus syndrome?

A

Subtype of MDS
Rare but important to recognise due to effective targeted therapy.
Relatively indolent clinical course

Rx: lenalidomide

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21
Q

When to suspect MDS?

A

Macrocytic anaemia or pancytopenia where vitamin B12 and folate deficiency have been excluded

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22
Q

How to diagnose MDS?

A

Bone marrow biopsy + aspiration for cytogenetic studies

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23
Q

What do you see on blood film in MDS?

A

Abnormal looking RBCs, white cells and platelets
□ Granulated platelets
□ Neutrophils with decreased nuclear segmentation and hypogranular cytoplasm (neutrophils usually release granules to sites of bacterial infection so even when they get to the site of infection they will be hypofunctional as they don’t have any granules to release from the cytoplasm)
□ Abnormal erythrocyte forms with Howell-Jolly bodies

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24
Q

What disease do you see Howell-Jolly bodies?

A

Erythrocytes in MDS

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25
Q

International prognostic scoring system (IPSS-R) is specifically used in which disease and what does it do?

A

MDS - predicts prognosis and informs therapy

Incorporates marrow blast, karyotype (chromosomal abnormality), cell counts ie cytopenia

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26
Q

What components make up the international prognostic scoring system?

A

Bone marrow blasts %
Genetic karyotype
Cytopenias (Hb count, platelet count, neutrophil count) )

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27
Q

How do you treat a low risk patient with MDS?

A

Most patients require no treatment at all or infrequent transfusions.

Red cell transfusion, platelet transfusion, tranaxemic acid, abx. Consider iron chelation therapy after 20 units of red cells.

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28
Q

How do you treat a high risk patient with MDS?

A

Goal is to prevent transformation to AML.
Azacitidine (low intensity chemotherapy) - needs 4/12 to see response/lack of response
Allogeneic bone marrow transplant (only curable option) - available age <60 or 60-70 and fit

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29
Q

Acute lymphoblastic leukaemia is the accumulation of …(…%) in the …

A

Lymphoblasts
20%
Bone marrow

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30
Q

What population do you see ALL?

A

Children

31
Q

What are the two types of ALL?

A

B-ALL (B cell) - most common

T-ALL (T cell)

32
Q

How to treat B-ALL?

A

Excellent response to chemotherapy

33
Q

Prognosis of B-ALL is based on…

A

Cytogenic abnormalities
T(12;21) has a good prognosis; more commonly seen in children
T(9;22) has a poor prognosis; more commonly seen in Adults (Philadelphia+ ALL)

34
Q

How does T-ALL present?

A

In teenagers as a thyme mass (called acute lymphoblastic lymphoma because it forms a mass)

35
Q

CLL is the neoplastic proliferation of …

A

lymphocytes (looks mature but functionally incompetent)

36
Q

Which is the most common adult leukaemia?

A

CLL

37
Q

What is the usual age group of CLL?

A

Elderly ~70 years

38
Q

How do people usually present with CLL?

A

60% asymptomatic with incidental lymphocytosis on FBC

39
Q

What are the symptoms of CLL?

A

Fatigue
Generalised lymphadenopathy
LOW
Recurrent sinusitis and respiratory infections (neoplastic naive B cells don’t produce immunoglobulins)

40
Q

What are the complications of CLL?

A
  1. Cytopenias (poor prognosis); due to infiltration of the BM by leukaemic cells
  2. Autoimmune haemolytic anaemia (all the abnormal immunoglobulins attach to RBCs)
  3. ITP
  4. Secondary skin cancers e.g. SCC, BCC (non-melanoma)
  5. 10% will transform into diffuse large cell lymphoma - fever, enlarging LN or spleen, raised LDH = aggressive!!
41
Q

In CLL, what do you think of someone develops isolated thrombocytopenia?

A

Immune thrombocytopenia purpura
If someone has isolated thrombocytopenia, it is most likely ITP and requires treatment for ITP. Only when they have refractory ITP, does it become an indication to treat CLL

42
Q

What do you see on blood film in CLL?

A

Smudge cells

Increased lymphocytes

43
Q

What would flow cytometry show in CLL?

A

Co expression of CD5+ (aberrant - this is a T cell marker), CD19+, CD23+

44
Q

Fluorescence in situ hybridisation (FISH) is done to help guide therapy in CLL because it detects genetic aberrations in >80% of the time. 2 important genetic mutations include …

A

17p deletion - poor prognosis, entitled to specific therapy
13q deletion - favourable prognosis

Helps decide which treatment to use
Only do FISH prior to starting treatment

45
Q

What’s the Rai system?

A

Staging system for CLL
Based on Hb and plat - when both <100, becomes more advanced stage

Not used much anymore

46
Q

List the poor prognostic markers of CLL.

A 
Raised LDH
Cytopenias 
17p deletion (via FISH)
Raised B2 microglobulin
TP53 inactivation (guardian gene) 
Unmutated IgH (B cells have not undergone maturation)
47
Q

What are the indications of CLL treatment?

A

Do not treat asymptomatic disease. Can be observed without therapy for decades.

ITP unresponsive to steroids
Worsening anaemia or thrombocytopenia
Massive/progressive/symptomatic splenomegaly or lymphadenopathy
Progressive lymphocytosis (>50% increase over 2 months) or lymphocyte doubling time <6 months `
Autoimmune haemolytic anaemia unresponsive to steroids
Symptomatic extranodal involvement
Constitutional symptoms

48
Q

How do you treat a young person with CLL?

A

FCR therapy (fluarabine + cyclophophamide + rituximab)

49
Q

How do you treat CLL in a young person with 17pdel or TP53 mutation?

A

Ibrutinib (compassionate access)

50
Q

How do you treat refractory CLL in a young person?

A

Ibrutinib or venetocloax

51
Q

What are 4 side effects of ibrutinib?

A

Lymphocytosis (can have WCC up to 200 which can stay elevated for months; this is ameliorated by rituximab but there is no evidence to use this)

Bruising ++ (WH 7 days prior to and after major surgery)

Diarrhoea

AF

52
Q

What class is ibrutinib?

A

TK inhibitor

53
Q

What class is venetocloax?

A

Bcl2 inhibitor

54
Q

How do you treat a frail elderly person with CLL?

A

Obinutuzumab (Type II anti-CD20 with enhanced ADCC) + venetocloax (bcl2 inhibitor)

55
Q

Hairy cell leukemia is the neoplastic proliferation of …

A

mature B cells characterised by hair cytoplasm projections

56
Q

How does hairy cell leukemia present?

A

Splenomegaly (due to accumulation of hairy cells in red pulp), “dry tap” on bone marrow aspirate (due to marrow fibrosis) and pancytopenia

Lymphadenopathy is usually absent

57
Q

Which type of leukemia has cells that are positive for tartrate-resistant acid phosphatase (TRAP)?

A

Hairy cell leukemia

58
Q

How do you treat hairy cell leukemia?

A

Excellent response to claribine (adenosine deaminase inhibitor - adenosine accumulates to toxic levels in neoplastic B cells)

Remission last for years

59
Q

3 early complications of AML

A

DIC
Hyperleucocytosis (WCC >100)
Febrile neutropenia

Lethal within weeks to months

60
Q

AML prognosis is largely guided by …

A

Genetic mutations

Categorises people into 3 groups based on genetic mutations. Guides treatment.
Favourable - can potentially achieve long term remission with induction and maintenance chemo alone

Intermediate

Adverse - seek urgent allogenic transplant, high failure rate of chemo alone

61
Q

List good and poor prognostic features of AML

A

Good
Good response to induction chemo
Lack of medical comorbidities
Young age

Poor
Myelodysplastic phase preceding AML
Older age >50 (more so >65-70)
Poor performance status

62
Q

Assessment of fitness in AML (to guide treatment

A

> =3 high risk of mortality during induction chemotherapy
Should rarely have it

Haematopoietic cell transplant comorbiditiy index

ECHO - LVEF

LFTs - raised bili and transaminases require chemo dose change

63
Q

Mutation analysis options in AML

A

FISH - rapid test - only used for dx of APML

Rapid PCR - FLT3, IDH, NPM

Next generation sequencing - panel to identify 20-30 mutations; determine prognosis and affect decision for transplant. However takes 2-6/52

64
Q

What does supportive care of AML entail?

A

1) Coagulopathy
- Monitor PT, APTT, Fib for signs of DIC
- Keep fibrinogen >1 (support with cryoprecipitate)

2) Tumour lysis prophylaxis
- BD monitoring of K+, phos, urate, LDH, Creatinine in high risk periods
- IVT +/- sodium bicarb
- Allopurinol
- Rasburicase

3) Central line
4) Neutrophil support with G-CSF until neutrophil recovery

5) Platelet, red cell transfusion support
- Irradiated cellular products if consideration of allo transplant (reduce risk of graft vs host disease)

9) Anti-infective prophylaxis
- Valciclovir protect against VZV, HSV
- Aspergillous over essential for induction AML (posaconazole)
- PJP cover with bactrim

7) Febrile neutropenia management
8) Drug interactions, toxicities
9) Nutrition
10) Fertility preservation - generally no time for this
11) Psychosocial

65
Q

What’s clonal cytopenias of undetermined significance (CCUS)?

A

Similar to MGUS in myeloma

Patient has cytopenia(s) but BM morphology not dysplastic, cytogenetics are normal

If an MDS type mutation is found, they have this condition. They are likely to progress to MDS.

66
Q

What’s clonal haematopoiesis of indeterminate potential (CHIP)?

A

Normal FBC
MDS-type mutation found for whatever reason

x2 more likely to have CAD, x4 more likely to develop acute MI

Risk of progression to MDS is not clear

67
Q

How does DIC in APML manifests?

A

Bleeding (not microvascular clotting in meningococcal sepsis)

68
Q

Management of DIC in APML

A

BD monitoring of fibrinogen

Replace fibrinogen with cryoprecipitate if fibrinogen <2

69
Q

Basophilia makes you think…

A

CML

70
Q

Clinical course of CLL

A

Slow progression

Rising lymphocytosis

Increasing lymphadenopathy and splenomegaly

Progressive BM failure/cytopenia

Immunosuppression of normal B cell production - hypoimmunoglobulinemia. Life threatening infections.

Autoimmune complications - ITP, autoimmune haemolytic anaemia

Skin cancers

71
Q

TK inhibitor mechanism of action in CLL

A

Bruton tyrosine kinase (BTK) plays a crucial role in B cell maturation

Blocks BTK = blocks BCR signalling/activation
Induces apoptosis, blocks migration/adherence

Get redistribution lymphocytosis (reduced by giving rituximab)

72
Q

How do BCL2 inhibitors work in CLL?

A

BCL over expression in CLL and follicular lymphoma

BCL2 inhibitors restores the cell’s ability to undergo apoptotic death. Cell death occurs quickly so need to increase dose slowly.

73
Q

What’s CAR T-cell?

A

New therapy

Take blood from patient –> extract out T cells –> modify T cells by attaching a man-made chimeric antigen receptor (CAR) to them so they recognise the tumour cells –> proliferate –> infuse modified T cells back to patient –> kills tumour cells

Each CAR is made for a specific cancer’s antigen
E.g. for leukemias and lymphomas that express CD19 antigen, CAR will be made to target cells with CD19 antigen specifically

74
Q

What is CAR T-cell approved for?

A

Relapsed/refractory B-ALL under 25 yo

Relapsed/refractory DLBCL

Haematology (7 decks)

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