Blood film: - Acute = >20% blasts - Myeloid = Auer rods Cytochemistry: - Myeloid = myeloperoxidase positive Immunophenotyping - Myeloid antigens

Blood film: - Acute =>20% blasts - Lymphoblastic = no auer rods Immunophenotyping: - B cell or T cell

Haematological Malignancies Flashcards by Renee Tuddenham

What is leukaemia?

Leukaemia cells in bone marrow

Circulate in peripheral blood

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What is Myelodysplasia?

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

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What are myeloproliferative disorders?

Excessive production of mature blood cells

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What are lymphomas?

Lymphoid cancers in lymphoid containing tissues

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What are plasma cell dyscrasias?

Increased plasma cells in the bone marrow

Increased plasma cells –> paraprotein formation –> end organ damage

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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

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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

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Environmental exposures associated with haematological malignancies

Chemotherapy - etoposide, anthracyclines, ASCT

-> AML
->MDS

Radiation

-> AML
-> CML
-> Mylodysplasia

Benzene exposure
–> Multiple myeloma

Hair dye
–> follicular lymphoma

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Familial haematological malignancies

Li Fraumeni - p53

Bloom syndrome - BLM gene

Runx1 –> acute leukaemia

GATA2 –> myelodysplasia

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Diagnosis of AML

Blood film:

Acute = >20% blasts
Myeloid = Auer rods

Cytochemistry:
- Myeloid = myeloperoxidase positive

Immunophenotyping
- Myeloid antigens

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Poor prognostic factors for AML

Age >60yrs

Cytogenetics:

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

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Good prognostic factors for AML

Cytogenetics:

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

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What if AML cells carry a normal genotype?

Molecular markers

Poor prognosis = Flt3 positive

Good prognosis = Flt3 negative and NPM1 positive

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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

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Diagnosis of ALL

Blood film:

Acute =>20% blasts
Lymphoblastic = no auer rods

Immunophenotyping:
- B cell or T cell

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Poor prognostic factors for ALL

Paediatric = 11q23 MLL translocations

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

Minimal residual disease post chemotherapy

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Good prognostic factors for ALL

Pediatric age group

Treatment of ALL

Induction chemotherapy –>
Maintenance chemotherapy

Allogenic BMT

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

Immunotherapies

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

Immunotherapies for ALL

CD20 positive = Rituximab

T cell mediated:

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

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

Clinical stages of CLL

1 = Lymphocytosis only
2 = Lymphadenopathy
3 = Cytopenias

1+2 = observe only
3 = Treat if symptoms

Prognosis of CLL

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

Good:
13q deletion

Treatment of CLL

Observe asymptomatic patients

Chemotherapy - oral or IV

p53 mutated = Alemtuzumab - OFF MARKET

Allogenic SCT

Trials

Can transform into ALL

Diagnosis of Myelodysplasia

Bone marrow failure - anaemia + neutropenia +/- thrombocytopenia +/- <20% blasts in the peripheral blood/BM Risk of transformation to AML

Classifications of Myelodysplasia

1. Refractory anaemia 2. 5q syndrome 3. CML - PB monocytes >1 4. MDS unclassified

Why is 5q syndrome different?

5q deletion only Females Better prognosis Treatment = lenolidomide

Treatment of myelodysplasia

Supportive - transfusions and iron chelation Chemotherapy for CML Allogenic SCT

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

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

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

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

Treatment of PCV and ET

Thrombosis --> mortality and morbidity Hydrea Aspirin Venesection Interferon alfa or chlorambucil

Treatment of myelofibrosis

Supportive: - Transfusion - Palliative chemotherapy - Splenectomy Allogenic SCT JAK1/2 inhibitor - Ruxolitinib - doesn't improve survival

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

Primary systemic amyloidosis

MGUS with attitude Amyloidogenic monoclonal protein Elevated serum free light chains Organ involvement - kidneys, heart, GIT, skin Treatment same as MM

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

Mechanism of action of Idelalisib?

Phosphoinositide-3-kinase inhibitor Used in combination with rituximab for relapsed CLL with p53 mutations

Mechanism of action of ruxolitinib?

JAK-2 kinase inhibitor PRV, ET and myelofibrosis treatment No mortality impact but reduces symtpoms

Mechanism of action of venetoclax?

BCL-2 homology region 3/BH3 mimetic For CLL with 17p deletion