Haem/Onc

Question 1

Chronic Lymphocytic Leukaemia
-Definition?
-Median age at diagnosis?
-Overexpression of what anti-apoptoic protein?
-Presentation?
-Signs?
-Abnormality in blood test?
-Blood film?
-Immunophenotyping markers?
-Cytogenetics good and poor prognosis?
-Standard treatment?
-Chemotherapy option?
-Immunotherapy option?

Answer 1

-Clonal expansion of B Lymphocytes
-70
-BCL2
-Asymptomatic/B signs
-Lymphadenopathy
-Lymphocytosis (+Anaemia/Thrombocytopenia in severe)
-Smudge Cells
-CD5+, CD19+, CD20+, CD 23+
-Del 13Q (Good prognosis) (Deletion 17Q Poor prognosis)
-Watchful waiting
-FCR (fludarabine, cyclophosphamide, rituximab)
-Ibrutinib (BTK Inhibitor) or Venetoclax (BCL-2 Inhibitor)

Question 2

Chronic Myeloid Leukaemia
-Definition?
-Median age of diagnosis?
-Pathophysiology?
-Symptoms?
-Blast crisis?
-Blood investigations?
-Thrombocytosis or thrombocytopenia?
-Peripheral blood smear?
-Why is LDH grossly elevated?
-Management?

Answer 2

-Myeloproliferative disorder caused by uncontrolled proliferation of myeloid stem cells
-50 to 60
-Translocation (9.22) leading to Philadelphia chromosome and formation of BCR-ABL1 fusion gene
-B Symptoms + Splenomegaly
-Transformation to acute leukemia (>20% blasts)
-Leucocytosis, granulocyte precursors Myelocytes + metamyelocytes), Basophilia, Eosinophilia,
-Thrombocytosis (early) Thrombocytopenia (Late)
-Predominance of mature granulocytes and precursors
-Increased cell turnover
-Tyrosine kinase inhibitors (Dasatinib -> Blocks BCR-ABL tyrosine kinase activity)

Question 3

Acute Myeloid Leukaemia
-Genetic risk factors?
-Cytogenetic abnormalities?
-Peripheral blood smear?
-Bone marrow biopsy?
-Induction therapy?

Answer 3

-Down syndrome+Fanconi syndrome
-T8:21, T15.17 (Acute promyelocytic leukaemia)
-Blast cells + Auer Rods (Posthegemonic)
-Over 20% blasts = diagnostic
-7 + 3 chemotherapy

Question 4

Myelodysplastic syndromes
-When to suspect?
-Diagnostic findings on BM biopsy?
-Best prognosis?
->20% blasts means?

Answer 4

-Macrocytic anaemias + Cytopenia’s in the elderly
-Bone marrow >10% dysplasia or ringed sideroblasts
-Del 5Q -> Tx with lenalidomide
-Progression to AML

Question 5

Myelofibrosis
-Driver mutations?
-Symptoms?
-Signs
-Peripheral blood smear?
-BM Biopsy?
-Targeted therapy?

Answer 5

-JAK2 (60%), CALR (20%), MPL (5%)
-B Symptoms
-Massive Splenomegaly
-Tear drop cells (Dacrocytes, circulating nucleated cells, Immature granulocytes)
-Fibrosis
-Ruxolitinib (JAK2 inhibitor)

Question 6

Burkitt’s lymphoma is an aggressive non-hodgkins lymphoma characterised by over expression of what gene?

Answer 6

c-MYc

Question 7

Overexpression of BCL2 is associated with what cancer?

Answer 7

B-Cell Non-Hodgkins lymphoma

Question 8

Hodgkins Lymphoma
-Epidemiology
-Most common subtype?
-Pathophysiology?
-Clinical features?
-Associated with what virus?
-Management
-Anti CD30 antibody used

Answer 8

-Bimodal (15-34) (>55)
-Nodular Sclerosis
-Reed-Sternberg cells
-B Symptoms + Lymphadenopathy
-EBV
-Chemo (ABVD) regime
-Brentuximab

Question 9

Hodgkins Lymphoma
Ann Arbor classification
Stage 1
Stage 2
Stage 3
Stage 4

Answer 9

1) Single lymph node
2) >2 Lymph node regions on the same diaphragm
3) Lymph node involvement both sides of diaphragm
4) Disseminated involvement

Question 10

T9:22

Answer 10

Chronic Myeloid Leukaemia

Question 11

T15:17

Answer 11

Acute pro-myelocytic leukaemia

Question 12

T14:18

Answer 12

Follicular Lymphoma

Question 13

T11:14

Answer 13

Mantle Cell Lymphoma

Question 14

Vincristine
1) MOA
2) Side effects

Answer 14

1) Inhibits formation of microtubules, Mitosis inhibitor (M stage of cell cycle)
2) Peripheral Neuropathy

Question 15

Cisplatin
1) MOA
2) Side effects

Answer 15

1) Cross linking in DNA
2) Ototoxicity, Hypomagnesemia

Question 16

Bleomycin
1) MOA
2) Side effects

Answer 16

1) Degrades preformed DNA
2) Lung fibrosis

Question 17

Doxorubicin
1) MOA
2) Side effects

Answer 17

1) Stabilises DNA-topoisomerase 2 complex. Inhibits DNA=RNA synthesis.
2) Cardiomyopathy

Question 18

Methotrexate
1) MOA
2) Side effects

Answer 18

1) Inhibits dihydrofolate reductase and thymidalate synthesis
2) Myelosuppression, Mucositis

Question 19

Cyclophosphamide
1) MOA
2) Side effects

Answer 19

1) Alkylating agent - cross linking in DNA
2) Haemorrhagic cystitis (Use Mensa to reduce incidence)

Question 20

Docetaxel
1) MOA
2) Side Effects

Answer 20

1) Prevents microtubule depolymerisation
2) Neutropenia + peripheral neuropathy

Question 21

Imatinib
1) MOA
2) Side effects

Answer 21

1) Inhibitor of tyrosine kinase associated with BCR-ABL defect
2) Cardiomyopathy

Question 22

Interferon-A
1) MOA
2) Side effects

Answer 22

1) Bind to interferon receptors, activation of JAK-STAT pathway
2) Flu like symptoms, depression, bone marrow suppression

Question 23

Cold AIHA
-Driven by what immunoglobulin?
-Intra vs Extra vascular

Answer 23

1) IgM
2) Intravascular

Question 24

Warm AIHA
1) Driven by what immunoglobulin?
2) Intra vs extra vascular?

Answer 24

1) IgG
2) Extravascular

Question 25

Young patient presents with mild anaemia, jaundice, splenomgally and pigment gallstones. Blood film = Spherocytes. Negative coombs test. Increased osmotic fragility. Associated with parvovirus B19

Answer 25

Hereditary Spherocytosis

Question 26

Sickle Cell Disease -Hydrophilic amino acid is replaced by what?

Answer 26

Glutamic acid (hydrophilic) is replaced with Valine (Hydrophobic)

Question 27

Types of Sickle Cell Crisis (TASH) 1) Thrombotic 2) Aplastic 3) Sequestration 4) Haemolytic

Answer 27

1) Vaso-occlusive crisis 2) Parvovirus B19 infection 3) Sickling within organs leading to acute chest syndrome (Tx Hydroxurea)

Question 28

Pernicious Anaemia 1) Definition? 2) Associated with which autoantibodies? 3) Blood film? 4) Type of anaemia?

Answer 28

1) Autoimmune cause of vitamin B12 deficiency due to loss of intrinsic factor from gastric parietal cell destruction 2) Anti-intrinsic factor + Anti-parietal cell antibodies 3) Hyper segmented neutrophils 4) Macrocytic

Question 29

Paroxysmal Nocturnal Haemoglobinuria (PMH) 1) Definition 2) Pathophysiology 3) Gold standard Ix? 4) Tx?

Answer 29

1) Intravascular haemolysis, thrombosis, bone marrow failure 2) Mutation in PIGA gene + deficiency in CD55 and CD59 3) Flow cytometry (Reduction in CD55+CD59) 4) Eculizumab (Monoclonal antibody against C5 compliment - reducing haemolysis)

Question 30

Classic blood film abnormality in Myelofibrosis?

Answer 30

"Tear drop" poikilocytes on blood film

Question 31

Acute Lymphoblastic leukaemia -If blast cell count is very high (>100) then what treatment is required prior to chemotherapy?

Answer 31

1) Leukapheresis -To prevent sludgin of capillary beds

Question 32

Prevention for high risk individuals from Tumour Lysis Syndrome?

Answer 32

1) Aggressive IV hydration 2) Allopurinol/Rasburicase

Question 33

Most commonly inherited thrombophilia?

Answer 33

Factor V Leiden

Question 34

Most commonly inherited bleeding disorder?

Answer 34

Von Willebrands

Question 35

What is a classical xray finding in Haemochromatosis?

Answer 35

Chondrocalcinosis

Question 36

What are the two reversible features of haemochromatosis with treatment?

Answer 36

Cardiomyopathy + Skin pigmentation

Question 37

Best assay to assess extrinsic coagulation pathway?

Answer 37

Prothrombin time (PT)

Question 38

Best assay to assess intrinsic pathway?

Answer 38

APTT