The Case Of The Worried Midwife + Samba-playing Grandmother

Question 1

Answer 1

Blood film reviewed by weekend on-call consultant:
• Neutropenia
• Marked thrombocytopenia
• Primitive myeloid blast cells
• Auer rods seen

Comment: morphology consistent with diagnosis of acute myeloid leukaemia – minimally differentiated blasts (FAB M1 subtype)

Question 2

symptoms of AML

Answer 2

Fatigue, SOB (anemia)
Bleeding, bruising (thrombocytopenia)
Infection (neutropenia)
DIC

Question 3

what do you seen on a blood film in AML?

Answer 3

primitive myeloid blast cells with Auer rods

Question 4

Auer rods

Answer 4

cytoplasmic inclusion bodies seen in AML (especially the promyelocytic type)

Question 5

how to diagnose AML?

Answer 5

how to diagnose AML

bone marrow biopsy

Question 6

what analysis is done with the bone marrow biopsy? (AML)

Answer 6

immunophenotyping

genetic, chromosomal and molecular analysis

Question 7

3 gene mutations common in AML

Answer 7

DNMT3A
FLT3
NPM1

Question 8

what affects prognosis in AML?

Answer 8

age at diagnosis

presence of gene mutations

Question 9

what gene mutations have a poor prognosis in AML?

Answer 9

p53 and FLT3 mutations

Question 10

treatment for AML

Answer 10

DA 3+10 chemotherapy regime
supportive therapy
allogeneic stem cell transplantation

Question 11

DA 3+10 regime

Answer 11

daunorubicin infusions on days 1, 3, 5

cytarabine infusions days 1-10

Question 12

what is supportive therapy for chemo patients?

Answer 12

platelet and red cell transfusions

prophylactic broad spectrum Abx and anti-fungals

Question 13

expected blood count after chemo?

Answer 13

pancytopenic for around 3 weeks

Question 14

injection of what can help blood counts recover after chemo?

Answer 14

granulocyte colony stimulating factor (GCSF)

Question 15

allogeneic transplantation

Answer 15

When a relative or unrelated person having a close HLA type is the donor.

Question 16

medical emergency caused by chemotherapy

Answer 16

medical emergency caused by chemotherapy

neutropenic sepsis

Question 17

which organisms are most dangerous in neutropenic sepsis?

Answer 17

gram negative e.g. pseudomonas

Question 18

treating neutropenic sepsis

Answer 18

blood cultures

blind Abx therapy, 1st line tazocin

Question 19

big complication of stem cell transplant?

Answer 19

graft vs host disease

Question 20

symptoms of graft vs host disease

Answer 20

skin rash
diarrhoea
liver failure

Question 21

How to prevent Graft vs Host disease?

Answer 21

T cell depletion of infused donor cells

immunosuppression of recipient

Question 22

graft vs leukemia effect

Answer 22

A small degree of graft v host can be good as donor WBCs fight and kill leuemia cells

Question 23

Acute Promyelocytic Leukemia

Answer 23

Subtype of AML, most curable of adult leukemias

Question 24

What is disseminated intravascular coagulation (DIC)?

Answer 24

release of procoagulant material causing abnormal clotting throughout the body

Question 25

common presentation of APML

Answer 25

they present with DIC or acute haemorrhage

Question 26

gene abnormality seen in APML

Answer 26

t(15;17) PML-RARA rearrangement

Question 27

prognosis of APML

Answer 27

80-90% 10yr survival

Question 28

what does PML-RARA translocation create?

Answer 28

fusion oncogene

Question 29

what is seen on blood film for APML?

Answer 29

what is seen on blood film for APML? | promyelocyte cells full of granules, prominent Auer rods

Question 30

treatment for APML

Answer 30

All-trans retinoic acid (ATRA) and arsenic trioxide

Question 31

mechanism of ATRA in APML?

Answer 31

binds to RARA and induces terminal differentiation of promyelocytes

Question 32

mechanism of arsenic trioxide

Answer 32

degrades the PML-RARA fusion protein, induces apoptosis of promyelocytes

Question 33

what monitoring is needed with ATRA-ATO regime?

Answer 33

QTc interval as arsenic can prolong it

Question 34

W hat % of AML is APML?

Answer 34

how much of AML is APML? | 11%

Question 35

complication of ATRA treatment?

Answer 35

differentiation syndrome | complication caused by a large, rapid release of cytokines from promyelocytes

Question 36

differentiation syndrome

Answer 36

complication caused by a large, rapid release of cytokines from promyelocytes

Question 37

symptoms of differentiation syndrome

Answer 37

``` fever dyspnoea hypoxia pleural effusions renal dysfunction ```

Question 38

treating differentiation syndrome?

Answer 38

corticosteroids e.g. dexamethasone

Question 39

what is a risk factor for differentiation syndrome ?

Answer 39

high white cell count

Question 40

what monitoring should you do after APML goes into remission?

Answer 40

minimal residual disease monitoring with PCR

Question 41

Chronic Myeloid Leukemia (CML)

Answer 41

a form of leukemia characterized by overproduction of granulocytes

Question 42

blood film in CML

Answer 42

myeloid cells at all stages of maturation

Question 43

symptoms of CML

Answer 43

symptoms of CML | mostly after age 50. fatigue, malaise, low grade fever, wt loss, bone pains. night sweats, splenomegaly

Question 44

treating CML

Answer 44

hydroxycarbamide hydration allopurinol dasatinib/imatinib

Question 45

gene mutation in CML

Answer 45

t(9;22) creating BCR-ABL

Question 46

BCR-ABL

Answer 46

tyrosine kinase oncogene - fusion protein

Question 47

Imatinib and dasatinib

Answer 47

Tyrosine kinase inhibitors of BCR-ABL

Question 48

life expectancy for CML

Answer 48

normal if on treatment

Question 49

purpose of hydroxycarbamide in CML treatment is to..

Answer 49

reduce white cell count

Question 50

Chronic Lymphocytic Leukemia (CLL)

Answer 50

a form of leukemia characterized by extremely high levels of lymphocytes; most often found in middle-age adults

Question 51

how do you diagnose CLL?

Answer 51

Flow cytometry

Question 52

how do you diagnose CLL?

Answer 52

fatigue, shortness of breath, night sweats, lymphadenopathy, splenomegaly

Question 53

what is the signature phenotype of CLL cells?

Answer 53

CD5 and CD19+ve B cells

Question 54

symptom staging system for CLL

Answer 54

Binet system A no impact B lymphadenopathy C reduction in Hb and/or platelets

Question 55

what determines management in CLL?

Answer 55

whether p53 is wild type, mutated or deleted

Question 56

treating CLL if wild type p53

Answer 56

standard chemo: fludarabine, cyclophosphamide, rituximab

Question 57

treating CLL if mutated p53

Answer 57

targeted therapy with ibrutinib, venetoclax or idelalisib

Question 58

ibrutinib

Answer 58

BTK inhibitor

Question 59

venetoclax

Answer 59

BCL-2 inhibitor

Question 60

Idelalisib

Answer 60

PI3K inhibitor

Question 61

how does venetoclax work?

Answer 61

inhibits BCL-2 which stops apoptosis so apoptosis of CLL cells can occur

Question 62

side effect of venetoclax

Answer 62

tumour lysis syndrome Massive release of cellular breakdown products, medical emergency

Question 63

Symptoms of tumour lysis syndrome Massive release of cellular breakdown products, medical emergency

Answer 63

``` nausea and vomiting arrythmias seizures AKI death ```

Question 64

treating tumour lysis syndrome

Answer 64

haemodialysis

Question 65

how to prevent tumor lysis syndrome

Answer 65

Pretreat with IV fluids and allopurinol or rasburicase

Question 66

Myeloproliferative disorders

Answer 66

a group of disorders considered clonal malignancies of the hematopoietic stem cell

Question 67

myelofibrosis

Answer 67

replacement of bone marrow by fibrous tissue

Question 68

primary myelofibrosis blood film

Answer 68

leucoerythroblastic, granulocyte left shift and teardrop red blood cells

Question 69

granulocyte left shift

Answer 69

increase in proportion of immature leucocytes

Question 70

symptoms of primary myelofibrosis

Answer 70

fatigue, shortness of breath, bloating, abdo discomfort (splenomegaly)

Question 71

What mutation is myelofibrosis associated with?

Answer 71

JAK2 V617F mutation

Question 72

treatment of primary myelofibrosis

Answer 72

hydroxycarbamide | Ruxolitinib

Question 73

Ruxolitinib… inhibitor

Answer 73

JAK2 inhibitor

Question 74

3 types of myeloproliferative disorders

Answer 74

primary myelofibrosis polycythaemia vera essential thrombocytothemia

Question 75

how does V617F mutation cause myeloproliferation?

Answer 75

permanently activates JAK2 tyrosine kinase so overproduction of red cells and platelets

Question 76

symptoms of multiple myeloma | CRAB:

Answer 76

hyperCalcemia Renal insufficiency Anemia Bone/Back pain

Question 77

investigations for multiple myeloma

Answer 77

``` FBC U&Es albumin LDH CRP electrophoresis light chain assay whole body MRI ```

Question 78

mechanism of multiple myeloma

Answer 78

infiltration of bone marrow by plasma cells, causes bone marrow failure

Question 79

Treating Multiple Myeloma

Answer 79

iv fluids pamidronate (if hypercalcaemia) haemodialysis chemotherapy

Question 80

chemotherapy for myeloma

Answer 80

Velcade, cyclophosphamide, thalidomide and dexamethasone

Question 81

how to confirm myeloma diagnosis

Answer 81

bone marrow biopsy showing plasma cell infiltration

Question 82

treating acute hypercalcaemia

Answer 82

hydration | pamidronate

Question 83

Pamidronate

Answer 83

Pamidronic acid or pamidronate disodium or APD, is a nitrogen-containing bisphosphonate used to prevent osteoporosis. Used in cancer

Question 84

what do plasma cells produce in multiple myeloma?

Answer 84

monoclonal Ig, usually IgG sometimes IgA

Question 85

what is light chain ratio in multiple myeloma?

Answer 85

abnormally skewed towards light chain

Question 86

Monoclonal gammopathy of undetermined significance (MGUS)

Answer 86

no CRAB symptoms and less than 10% plasma cell infiltration | watch and wait

Question 87

treating multiple myeloma?

Answer 87

chemotherapy | autologous stem cell transplant