Haematological Malignancies Flashcards
What is leukaemia?
Leukaemia cells in bone marrow
Circulate in peripheral blood
What is Myelodysplasia?
Insufficient production of mature blood cells +/- leukaemia in the peripheral blood/bone marrow
What are myeloproliferative disorders?
Excessive production of mature blood cells
What are lymphomas?
Lymphoid cancers in lymphoid containing tissues
What are plasma cell dyscrasias?
Increased plasma cells in the bone marrow
Increased plasma cells –> paraprotein formation –> end organ damage
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
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
Environmental exposures associated with haematological malignancies
Chemotherapy - etoposide, anthracyclines, ASCT
- -> AML
- ->MDS
Radiation
- -> AML
- -> CML
- -> Mylodysplasia
Benzene exposure
–> Multiple myeloma
Hair dye
–> follicular lymphoma
Familial haematological malignancies
Li Fraumeni - p53
Bloom syndrome - BLM gene
Runx1 –> acute leukaemia
GATA2 –> myelodysplasia
Diagnosis of AML
Blood film:
- Acute = >20% blasts
- Myeloid = Auer rods
Cytochemistry:
- Myeloid = myeloperoxidase positive
Immunophenotyping
- Myeloid antigens
Poor prognostic factors for AML
Age >60yrs
Cytogenetics:
- t(9:22)
- Del7, del5q, inv(3)
- Complex cyogenetics >2 abnormalities
Good prognostic factors for AML
Cytogenetics:
- t (15:17) = APML
- inv (16)
- t (8:21)
What if AML cells carry a normal genotype?
Molecular markers
Poor prognosis = Flt3 positive
Good prognosis = Flt3 negative and NPM1 positive
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
Diagnosis of ALL
Blood film:
- Acute =>20% blasts
- Lymphoblastic = no auer rods
Immunophenotyping:
- B cell or T cell
Poor prognostic factors for ALL
Paediatric = 11q23 MLL translocations
Adult:
= T (9:22)
= Bcr-Abl
Minimal residual disease post chemotherapy
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
- Refractory anaemia
- 5q syndrome
- CML - PB monocytes >1
- 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
