Haematology Flashcards
Therapy related AML/MDS
1) Alkylating agents
- Cyclophosphamide
- Melphalan
- Busulfan
2) Topoisomerase II inhibitors
- Etoposide (testicular cancer)
- Mitoxantrone
EBV and lymphomas
Predominantly in the immunocompromised host
- Burkitt
- Hodgkins
- DLBCL
- PCNSL
- Plasmablastic lymphoma
BCR ABL - Philadelphia chromosome
translocation 9:22 –> deregulated tyrosine kinase activity
Note PCR of BCR-ABL can be used to monitor for molecular response.
Polycythemia driver genes
1) JAK 2
- V617F (96%)
- exon 12 (4%)
Lab findings in PCV
1) Elevated HB (16.5 male/16.0 female)
2) Suppressed endogenous EPO
3) Iron deficiency (functional iron deficiency)
Low risk PCV
1) <65
2) No hx associated arterial or venous thrombosis
Aspirin only
High risk
1) >65
2) Prior PV associated arterial or venous thrombosis
Aspirin Cytoreductive therapy - Venesection - Hydroxeurea - Interferon
Essential thrombocytopenia
1) Jak 2 (60-65%)
2) CALR
3) MPL
Triple negative = low risk of vascular events
Mgmt Aspirin
Primary myelofibrosis genetics chanegs
1) Jak 2 (60-65%)
2) CALR
3) MPL
Clinical findings for Primary Myelofibrosis
1) Anaemia
2) Leukocytosis
3) raised LDH
4) Splenomegaly
Management of PM
1) Supportive
2) JAK 2 inhibitors (ruxolitinib)
3) Allogenic stem cell transplant
Treatment for CML
1) TKI: imatanib, dasatanib
Main adverse effect of dasatanib
Pleural and pericardial effusions
CMML Chronic myelomonocytic leukaemia
1) Leukocytosis + monocytosis
2) Absence of driver mutations (JAK2/BCR-ABL)
Treatment for CMML
1) Supportive
2) Cytoreductive therapy i.e hydroxyurea
3) Hypomethylating agents i.e azacitadine
What do you treat 5q deletion MDS with?
Lenolidamide
MDS treatment (non-5q) for poor ECOG/older patients
1) Tranfusion support
- Blood transfusion
- Platelet tranfusion
2) Growth factors
- Erythropoiesis stimulating agents
- Granulocyte colony stimulating factor
GATA 2 germline mutation (not complete)
Note all will develop MDS therefore early transplant
Disease modifying agents for low risk MDS
1) Activin receptor type II ligand traps: Luspatercept/Sotatercept
MOA; fusion protein that blocks transforming growth factor - TGF B- that inhibits erythropoiesis
Disease modifying agents in high risk MDS
1) Azacitadine: hypomethylating agent
AML diagnosis
1) Pancytopenia
2) > 20% blasts in aspirate
3) Blasts with Bauer rods
Flt 3 ITD mutation in AML good or poor prognosis
Confers poor prognosis
NPM1 + FLT 3 = better prognosis
Treatment for AML (low ECOG)
Induction
3 days anthracycline
7 days cytarabine
Allogenic stem cell transplant
Treatment for AML (high ECOG or age >70)
Low dose cytarabine
Azactiadine - less than 30% blasts (due to slow cytoreduction)
Targeted therapies in AML
1) FLT 3 mutation: Midostaurin
2) ABT-199: Venetoclax + Azacitadine
APML
PML RARA fusion –> blockage of pro-myelocytes non differentiation and no maturation
15:17
Blood film findings on APML
Bilobed nucleoli
Hypo/hyperganulated cytoplasma
Treatment for APML
1) Atra –> degrades fusion gene –> allows differentiation 2) Arsenic
3) Identify and monitor for DIC
ALL diagnostic criteria
20% blasts in bone marrow
No auer rods in blasts
Nb immunophenotyping via flow cytometry
Poor prognostic factors in ALL
B-ALL - BCR-ABL - Philadelphia like (no BCR-ABL) T-ALL - Early thymocyte precursor phenotype
In all lineages older age = poorer prognosis
Chronic lymphocytic leukaemia diagnosis
1) Lymphocytosis (B-cell lymphocytes) +/- cytopenias
2) CD5 and CD19 clonal B cells
Good prognosis in CLL
13q deletion (“the lucky deletion)
Poor prognosis in CLL
11q/17p deletion
Zap-70
CD38+
Unmutated heavy chain gene
When to treat CLL
1) Cytopenias
2) Lymphocyte doubled in <6 months or >50% increase in 2 months
3) Disease related symptoms
4) Autoimmune complications
Richters transformation in CLL
Tranformation to lymphoma ie DLBCL
Treatment CLL
1) Without deletion of 17p (TP53 mutation)
- Chemotherapy
2) With deletion of 17p
- Immunotherapy; Ibrutinib/Venetoclax
MOA of Venetoclax
Inhibits BCL-2 which is an anti-apoptotic protein that is over expressed in CLL
Diagnosis of Systemic AL Amyloidosis
Biopsy with Congo red stain
Criteria for Myeloma
1) Bone marrow >10% clonal plasma cells
2) End organ damage
- CRAB
- SLIM
SLIM criteria for MM
S: Sixty percent of=r greater clonal plasma cells on bone marrow
LI: Free Light chain ratio >100
M: MRI demonstrate one focal lesion that is at least 5mm or greater in size
Prognostic markers for MM
B2 microglobulin < 3.5 good > 5 bad Albumin > 35 good < 35 bad
Main adverse effects of carlifilzomib
Heart failure
Pathogenesis of Burkitt Lymphoma
Translocation of the MYC oncogene from chromosome 8
- T(8:14)
- T(2:8)
- T(8:22)
Follicular Lymphoma translocation
T14:18
Leads to BCL over expression
GELF criteria for commencement of chemo-immunotherapy
Symptomatic disease
Threatened end organ damage
Bulky disease
Which gene mutation has been identified in WM
MYD88
Complications associated with IGM MGUS
1) Perhiperal neuropathy
2) Cryoglobulinaemia
3) Hyperviscosity syndrome
4) Malabsorption - from depositing in GIT
Histological findings in Hodgkins Lymphoma
1) Reed Sternberg cells
2) CD30 positive
Brentuximab MOA and use
Anti-CD30
Used for relapsed refractory Hodgkins lymphoma
Emicizumab Mechanism of action
Monoclonal antibody that binds activated IX to X thus bypassing the need of activated factor VIII
Used for haemophilia A
What does prothrombinex contain in Australia?
coagulation factors II, IX and X and low levels of factors V and VII
TTP
Headaches
Plasmapharesis
HLH
Elevated Ferritin
Haemophagocytosis on blood film
Felty’s
RA/Splenomegaly/Neutropenia
Spur cell haemolytic anaemia
Cholesterol deposition in RBC cell membranes from Apo-lipoprotein A2
Spur cell –> Extravascular Haemolysis
B12 Deficiency
Megaloblastic Anaemia
Hyper-segmented neutrophils
Post gastrectomy common
Promthrombinex inclusion
2/7/9/10
Erlenmyer Flask Abnormality
Gaucher Disease (Inherited disease of storage)
CART cells
CD 19
Cytokine release syndrome
