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Scientific Basis of Medicine > The Case Of The Worried Midwife + Samba-playing Grandmother > Flashcards

The Case Of The Worried Midwife + Samba-playing Grandmother Flashcards

1
Q
A 
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)

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2
Q

symptoms of AML

A

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

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3
Q

what do you seen on a blood film in AML?

A

primitive myeloid blast cells with Auer rods

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4
Q

Auer rods

A

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

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5
Q

how to diagnose AML?

A

how to diagnose AML

bone marrow biopsy

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6
Q

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

A

immunophenotyping

genetic, chromosomal and molecular analysis

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7
Q

3 gene mutations common in AML

A

DNMT3A
FLT3
NPM1

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8
Q

what affects prognosis in AML?

A

age at diagnosis

presence of gene mutations

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9
Q

what gene mutations have a poor prognosis in AML?

A

p53 and FLT3 mutations

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10
Q

treatment for AML

A

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

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11
Q

DA 3+10 regime

A

daunorubicin infusions on days 1, 3, 5

cytarabine infusions days 1-10

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12
Q

what is supportive therapy for chemo patients?

A

platelet and red cell transfusions

prophylactic broad spectrum Abx and anti-fungals

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13
Q

expected blood count after chemo?

A

pancytopenic for around 3 weeks

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14
Q

injection of what can help blood counts recover after chemo?

A

granulocyte colony stimulating factor (GCSF)

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15
Q

allogeneic transplantation

A

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

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16
Q

medical emergency caused by chemotherapy

A

medical emergency caused by chemotherapy

neutropenic sepsis

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17
Q

which organisms are most dangerous in neutropenic sepsis?

A

gram negative e.g. pseudomonas

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18
Q

treating neutropenic sepsis

A

blood cultures

blind Abx therapy, 1st line tazocin

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19
Q

big complication of stem cell transplant?

A

graft vs host disease

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20
Q

symptoms of graft vs host disease

A

skin rash
diarrhoea
liver failure

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21
Q

How to prevent Graft vs Host disease?

A

T cell depletion of infused donor cells

immunosuppression of recipient

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22
Q

graft vs leukemia effect

A

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

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23
Q

Acute Promyelocytic Leukemia

A

Subtype of AML, most curable of adult leukemias

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24
Q

What is disseminated intravascular coagulation (DIC)?

A

release of procoagulant material causing abnormal clotting throughout the body

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25
Q

common presentation of APML

A

they present with DIC or acute haemorrhage

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26
Q

gene abnormality seen in APML

A

t(15;17) PML-RARA rearrangement

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27
Q

prognosis of APML

A

80-90% 10yr survival

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28
Q

what does PML-RARA translocation create?

A

fusion oncogene

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29
Q

what is seen on blood film for APML?

A

what is seen on blood film for APML?

promyelocyte cells full of granules, prominent Auer rods

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30
Q

treatment for APML

A

All-trans retinoic acid (ATRA) and arsenic trioxide

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31
Q

mechanism of ATRA in APML?

A

binds to RARA and induces terminal differentiation of promyelocytes

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32
Q

mechanism of arsenic trioxide

A

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

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33
Q

what monitoring is needed with ATRA-ATO regime?

A

QTc interval as arsenic can prolong it

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34
Q

W hat % of AML is APML?

A

how much of AML is APML?

11%

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35
Q

complication of ATRA treatment?

A

differentiation syndrome

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

36
Q

differentiation syndrome

A

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

37
Q

symptoms of differentiation syndrome

A 
fever
dyspnoea
hypoxia
pleural effusions
renal dysfunction
38
Q

treating differentiation syndrome?

A

corticosteroids e.g. dexamethasone

39
Q

what is a risk factor for differentiation syndrome ?

A

high white cell count

40
Q

what monitoring should you do after APML goes into remission?

A

minimal residual disease monitoring with PCR

41
Q

Chronic Myeloid Leukemia (CML)

A

a form of leukemia characterized by overproduction of granulocytes

42
Q

blood film in CML

A

myeloid cells at all stages of maturation

43
Q

symptoms of CML

A

symptoms of CML

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

44
Q

treating CML

A

hydroxycarbamide
hydration
allopurinol
dasatinib/imatinib

45
Q

gene mutation in CML

A

t(9;22) creating BCR-ABL

46
Q

BCR-ABL

A

tyrosine kinase oncogene - fusion protein

47
Q

Imatinib and dasatinib

A

Tyrosine kinase inhibitors of BCR-ABL

48
Q

life expectancy for CML

A

normal if on treatment

49
Q

purpose of hydroxycarbamide in CML treatment is to..

A

reduce white cell count

50
Q

Chronic Lymphocytic Leukemia (CLL)

A

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

51
Q

how do you diagnose CLL?

A

Flow cytometry

52
Q

how do you diagnose CLL?

A

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

53
Q

what is the signature phenotype of CLL cells?

A

CD5 and CD19+ve B cells

54
Q

symptom staging system for CLL

A

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

55
Q

what determines management in CLL?

A

whether p53 is wild type, mutated or deleted

56
Q

treating CLL if wild type p53

A

standard chemo: fludarabine, cyclophosphamide, rituximab

57
Q

treating CLL if mutated p53

A

targeted therapy with ibrutinib, venetoclax or idelalisib

58
Q

ibrutinib

A

BTK inhibitor

59
Q

venetoclax

A

BCL-2 inhibitor

60
Q

Idelalisib

A

PI3K inhibitor

61
Q

how does venetoclax work?

A

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

62
Q

side effect of venetoclax

A

tumour lysis syndrome

Massive release of cellular breakdown products, medical emergency

63
Q

Symptoms of tumour lysis syndrome

Massive release of cellular breakdown products, medical emergency

A 
nausea and vomiting
arrythmias
seizures
AKI
death
64
Q

treating tumour lysis syndrome

A

haemodialysis

65
Q

how to prevent tumor lysis syndrome

A

Pretreat with IV fluids and allopurinol or rasburicase

66
Q

Myeloproliferative disorders

A

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

67
Q

myelofibrosis

A

replacement of bone marrow by fibrous tissue

68
Q

primary myelofibrosis blood film

A

leucoerythroblastic, granulocyte left shift and teardrop red blood cells

69
Q

granulocyte left shift

A

increase in proportion of immature leucocytes

70
Q

symptoms of primary myelofibrosis

A

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

71
Q

What mutation is myelofibrosis associated with?

A

JAK2 V617F mutation

72
Q

treatment of primary myelofibrosis

A

hydroxycarbamide

Ruxolitinib

73
Q

Ruxolitinib… inhibitor

A

JAK2 inhibitor

74
Q

3 types of myeloproliferative disorders

A

primary myelofibrosis
polycythaemia vera
essential thrombocytothemia

75
Q

how does V617F mutation cause myeloproliferation?

A

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

76
Q

symptoms of multiple myeloma

CRAB:

A

hyperCalcemia
Renal insufficiency
Anemia
Bone/Back pain

77
Q

investigations for multiple myeloma

A 
FBC
U&Es
albumin
LDH
CRP
electrophoresis
light chain assay
whole body MRI
78
Q

mechanism of multiple myeloma

A

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

79
Q

Treating Multiple Myeloma

A

iv fluids
pamidronate (if hypercalcaemia)
haemodialysis
chemotherapy

80
Q

chemotherapy for myeloma

A

Velcade, cyclophosphamide, thalidomide and dexamethasone

81
Q

how to confirm myeloma diagnosis

A

bone marrow biopsy showing plasma cell infiltration

82
Q

treating acute hypercalcaemia

A

hydration

pamidronate

83
Q

Pamidronate

A

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

84
Q

what do plasma cells produce in multiple myeloma?

A

monoclonal Ig, usually IgG sometimes IgA

85
Q

what is light chain ratio in multiple myeloma?

A

abnormally skewed towards light chain

86
Q

Monoclonal gammopathy of undetermined significance (MGUS)

A

no CRAB symptoms and less than 10% plasma cell infiltration

watch and wait

87
Q

treating multiple myeloma?

A

chemotherapy

autologous stem cell transplant

Scientific Basis of Medicine (35 decks)

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