Haematological Malignancies Flashcards Preview

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Flashcards in Haematological Malignancies Deck (40):
1

What is leukaemia?

Leukaemia cells in bone marrow
Circulate in peripheral blood

2

What is Myelodysplasia?

Insufficient production of mature blood cells +/- leukaemia in the peripheral blood/bone marrow

3

What are myeloproliferative disorders?

Excessive production of mature blood cells

4

What are lymphomas?

Lymphoid cancers in lymphoid containing tissues

5

What are plasma cell dyscrasias?

Increased plasma cells in the bone marrow
Increased plasma cells --> paraprotein formation --> end organ damage

6

Effects of blood cancers on the body?

Formation of cancerous cells
Loss of production of other blood cell lines
Hepatosplenomegaly
Lymphadenopathy --> compressive symptoms
Orthopaedic complications - fractures, bone pain
Neurologic complications
Metabolic complications - calcium and urate

7

Viruses associated with haematological malignancies?

EBV
--> Hodgkins lymphoma
--> Burkitt lymphoma
--> Post-transplant lymphporliferative disorder

HTLV-1
--> Acute T lymphoblastic leukaemia/lymphoma

HIV
--> Cerebral Diffuse Large B Cell Lymphoma
--> Hodgkin lymphoma
--> Diffuse large B cell lymphoma

HHV-6
--> Primary effusion lymphoma

8

Environmental exposures associated with haematological malignancies

Chemotherapy - etoposide, anthracyclines, ASCT
--> AML
-->MDS

Radiation
--> AML
--> CML
--> Mylodysplasia

Benzene exposure
--> Multiple myeloma

Hair dye
--> follicular lymphoma

9

Familial haematological malignancies

Li Fraumeni - p53

Bloom syndrome - BLM gene

Runx1 --> acute leukaemia

GATA2 --> myelodysplasia

10

Diagnosis of AML

Blood film:
- Acute = >20% blasts
- Myeloid = Auer rods

Cytochemistry:
- Myeloid = myeloperoxidase positive

Immunophenotyping
- Myeloid antigens

11

Poor prognostic factors for AML

Age >60yrs

Cytogenetics:
- t(9:22)
- Del7, del5q, inv(3)
- Complex cyogenetics >2 abnormalities

12

Good prognostic factors for AML

Cytogenetics:
- t (15:17) = APML
- inv (16)
- t (8:21)

13

What if AML cells carry a normal genotype?

Molecular markers

Poor prognosis = Flt3 positive

Good prognosis = Flt3 negative and NPM1 positive

14

Treatment of AML

Prognostic factors at diagnosis = treatment strategy

If good health = chemotherapy --> Allogenic BMT
If poor health = supportive care

Relapse = Allogenic BMT or trials

15

Diagnosis of ALL

Blood film:
- Acute =>20% blasts
- Lymphoblastic = no auer rods

Immunophenotyping:
- B cell or T cell

16

Poor prognostic factors for ALL

Paediatric = 11q23 MLL translocations

Adult:
= T (9:22)
= Bcr-Abl

Minimal residual disease post chemotherapy

17

Good prognostic factors for ALL

Pediatric age group

18

Treatment of ALL

Induction chemotherapy -->
Maintenance chemotherapy

Allogenic BMT

If Bcr-Abl --> Bcr-Abl inhibitor - imatinib, dasatinib

Immunotherapies

19

Limitations of Allogenic BMT

Appropriate donor
Suitable recipient for transplant

Acute graft vs host disease
Chronic graft vs host disease

Infections
Treatment toxicity

Relapse post transplant

20

Immunotherapies for ALL

CD20 positive = Rituximab

T cell mediated:
- CD19/CD3 = Blinotumomab
- Chimeric antigen receptor modified T cell infusions

21

Diagnosis pf CLL

Lymphadenopathy

Blood film:
- Many mature lymphocytes on peripheral BF
- Smear cells
- Haemolysis --> spherocytes
- Thrmbocytopenia
- BM faliure

Immunophenotyping:
- Lymphocytes kappa or lamba light chain restricted

22

Clinical stages of CLL

1 = Lymphocytosis only
2 = Lymphadenopathy
3 = Cytopenias

1+2 = observe only
3 = Treat if symptoms

23

Prognosis of CLL

Poor:
11q and 17p deletions
Unmutated IgVH genes
ZAP-70 expression - associated with unmutated IgVH

Good:
13q deletion

24

Treatment of CLL

Observe asymptomatic patients

Chemotherapy - oral or IV

p53 mutated = Alemtuzumab - OFF MARKET

Allogenic SCT

Trials

Can transform into ALL

25

Diagnosis of Myelodysplasia

Bone marrow failure - anaemia + neutropenia +/- thrombocytopenia

+/- <20% blasts in the peripheral blood/BM

Risk of transformation to AML

26

Classifications of Myelodysplasia

1. Refractory anaemia

2. 5q syndrome

3. CML - PB monocytes >1

4. MDS unclassified

27

Why is 5q syndrome different?

5q deletion only

Females

Better prognosis

Treatment = lenolidomide

28

Treatment of myelodysplasia

Supportive
- transfusions and iron chelation

Chemotherapy for CML

Allogenic SCT

29

Classifications of Lymphoma

Hodgkins Lymphoma and Non-Hodgkins Lymphoma

Indolent NHL
- Marginal zone
- Follicular
TREAT ONLY IF SYMPTOMS

Aggressive NHL
- Diffuse large B cell lymphoma
- Burkitt Lymphoma
TREAT - RCHOP chemo +/-radio OR ASCT

30

Hodgkins Lymphoma

Reed sternberg cells on histology

Prognosis and treatment based on Ann arbor staging

Chemotherapy and targeted radiotherapy

Relapse/refractory = Autologous SCT
Anti-CD30 Ab - brentuximab
PD-1 inhibitors

31

Types of myeloproliferative disorders

CML
- Neutrophilia +/- basophilia
- Bcr-ABL postive

Polycythaemia Rubra Vera
- High RBC mass
- Headaches and erythromelalgia

Essential Thrombocytosis
- Elevated platelets
- Clots and vascular disease

Myelofibrosis
- low counts
- Leukoerythoblastic film

32

Gene mutations in MPN

CML = Bcr-Abl
= Treatment with imatinib, nilotinib or dasatinib

PV and ET and MF = JAK2 V617F

If JAK2 negative ET and MF = Calreticulin positive
Good prognosis

33

Treatment of PCV and ET

Thrombosis --> mortality and morbidity

Hydrea
Aspirin
Venesection
Interferon alfa or chlorambucil

34

Treatment of myelofibrosis

Supportive:
- Transfusion
- Palliative chemotherapy
- Splenectomy

Allogenic SCT

JAK1/2 inhibitor - Ruxolitinib - doesn't improve survival

35

Multiple Myeloma

>10% malignant plasma cells on bone marrow
Monoclonal Ig in serum or urine - IgG>IgA>IgM>IgD

Treat if organ involvement - CRAB

Treatment :
- Chemotherapy
- Lenolidomide
- Bortezomib - proteosome inhibitors

- Autologous SCT

- Radiotherapy for bone lesions
- Bisphosophonates for bone lesions

36

Primary systemic amyloidosis

MGUS with attitude
Amyloidogenic monoclonal protein
Elevated serum free light chains

Organ involvement - kidneys, heart, GIT, skin

Treatment same as MM

37

Mechanism of action of ibrutinib?

Bruton's tyrosine kinase inhibitor

Used to treat B cell cancers - mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia - NHL

38

Mechanism of action of Idelalisib?

Phosphoinositide-3-kinase inhibitor

Used in combination with rituximab for relapsed CLL with p53 mutations

39

Mechanism of action of ruxolitinib?

JAK-2 kinase inhibitor

PRV, ET and myelofibrosis treatment
No mortality impact but reduces symtpoms

40

Mechanism of action of venetoclax?

BCL-2 homology region 3/BH3 mimetic

For CLL with 17p deletion