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B9W6 > PBL 1 > Flashcards

PBL 1 Flashcards

1
Q

what are the 4 main types of leukaemia?

A

acute lymphoblastic
acute myeloid
chromic lymphocytic
chronic myeloid

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2
Q

what types of leukaemia is most common in children?

A

acute lymphoblastic

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3
Q

what are the 2 types of acute lymphoblastic anaemia?

A

T-cell ALL and B-cell ALL

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4
Q

which lymphoid cells does chronic lymphocytic leukaemia affect?

A

B cells

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5
Q

what do haematopoetic stem cells give rise to?

A

myeloblasts and lymphoblasts

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6
Q

what do myeloblasts give rise to?

A

erythrocytes, thrombocytes, monocytes, granulocytes

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7
Q

what do lymphoblasts give rise to?

A

pre-B cells, pre-T cells and natural killer cells

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8
Q

what are leukocyte examples?

A 
neutrophil
basophil
eosinophil
B lymphocyte
NK cell
T lymphcyte 
monocytes 
macrophages
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9
Q

outline the cause of ALL?

A

chromosomal trabslocation of chromosomes 9 and 22 or 12 and 21, or an abnormal chromosome number which results in the formation of abnormal proteins which affect cell’s ability to differentiate, so they remain as blast cells which cannot fucntion correctly. this causes uncontrollable division and crowds out other cells in the bone marrow and blood. Some blasts will settle in organs and tissues

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10
Q

what are the symptoms of ALL and AML?

A 
fatigue
anaemia
frequent infections due to leukopenia
easy bleeding/bruising due to thrombocytopenia
feeling of abdominal fullness/dragging due to hepatosplenomegaly
lymph node pain due to lymphadenopathy
bone pain due to swelling of bone marrow
swelling of gums in monocytic AML
thymus enlargement in T-cell ALL
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11
Q

outline the pathophysiology of AML?

A

caused by a variety of things e.g. chromosomal translocation. the mutation causes the precursor blood cells to lose their ability to differentiate so they remain as blast cells that don’t function effectively, the mutation also causes uncontrollable division of blast cells and crowds out other cells
Blast cells spill out into the blood and some settle in organs and tissues

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12
Q

what does the FLT3 gene code for?

A

A protein called FLT3 that helps white blood cells grow.

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13
Q

what hapens if we get a mutation in FLT3?

A

the growth of too many abnormal leukemia cells. which can be a cause of acute myeloid leukaemia

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14
Q

outline the classification of AML?

A 
M0- AML without maturation
M1- AML with minimal maturation
M2- AML with maturation
M3- acute promyelocytic leukaemia
M4- acute myelomonocytic leukaemia
M5- acute monocytic leukaemia
M6- acute erythroid leukaemia
M7- acute megakaryoblastic leukaemia
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15
Q

what is AML with maturation?

A

> 20% blasts in the bone marrow or blood and evidence of maturation to more mature neutrophils

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16
Q

what is AML wihtout maturation?

A

a high percentage of blasts in the bone marrow without significant evidence of myeloid maturation.

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17
Q

what is acute promyelocytic leukaemia?

A

When there are too many promyelocytes (immature blood-forming cells) in the blood and bone marrow which leads to a shortage of normal blood cells in the body.

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18
Q

what is acute myelomonocytic leukaemia?

A

a rare type of AML in which there is an increased production of immature neutrophil and monocytes in the bone marrow.

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19
Q

what is acute monocytic leukaemia?

A

a subtype of AML, in which >80% of the affected blood cells are a type of white blood cell called monocytes

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20
Q

what is acute erythroid leukaemia?

A

a rare form of acute myeloid leukemia where the myeloproliferation is of erythroblastic precursors

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21
Q

what is acute megakaryoblastic leukaemia?

A

a rare form of acute myeloid leukemia (AML), which is characterized by proliferation of ≥20% megakaryoblasts

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22
Q

whats the pathophysiology of acute promyelocytic leukaemia?

A

translocation of chromosomes 15 and 17 which disrupts the retinoic acid receptor alpha gene which is required for normal cell division. This activates the normal clotting process but because of the decreased platelets we get disseminated intravascular coagulation

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23
Q

what are the risk fcators for acute leukaemia?

A

getting older >50
being male
being exposed to certain chemicals e.g. benzene in cigarettes
being treated with certain chemotherapy drugs
being exposed to radiation
having certain blood disorders
certain genetic syndromes e.g. Down syndrome
race - more common in African Americans

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24
Q

what will a peripheral blood smear look like in AML?

A

myeloblasts - large cells with round-oval nucleus with fine chromatin and 2-4 nuclei
normocytic anaemia
>20% myeloblasts
myeloblasts will contain Auer rods - crystalline cytoplasmic inclusions
moderate-severe thrombocytopenia

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25
Q

what will a peripheral blood stain for ALL look like

A

lymphoblasts will be large cells with round-oval nucleus, clumped chromatin
normocytic anaemia
>20% lymphoblasts
thrombocytopenia

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26
Q

how do we diagnose acute leukaemia?

A 
peripheral blood smear
bone marrow biopsy
lymph node biopsy
immunophenotyping
G-banding
FISH
PCR
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27
Q

what is immunophenotyping?

A

uses antibodies to identify cells based on the types of antigens or markers on the surface of the cells.

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28
Q

what is G-banding?

A

The banding pattern can distinguish chromosomal abnormalities or structural rearrangements, such as translocations, deletions, insertions, and inversions.

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29
Q

what is FISH?

A

fluorescence in situ hybridization

looks for a small number of specific changes in genes or chromosomes

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30
Q

what are the subtypes of ALL?

A

ALL-L1 - small, uniform cells, nuclei have condensed chromatin
ALL-L2 - most common, large, hereogenous cells, nuclei irregular
ALL-L3 - large, homogeneous cells, regular nuclei

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31
Q

what are the treatment options for acute leukaemia?

A 
chemotherapy e.g. vincristine
regular blood transfusions
antibiotics
biological therapy
stem cell transplants
bone marrow transplants
radiotherapy
all-trans-retinoic acid 
arsenic trioxide
32
Q

what are the 2 stages for treating acute leukaemia?

A

induction - treatment aims to kill as many leukaemia cells as possible
consolidation - treatment aims to prevent relapse

33
Q

what is All-Trans-Retinoic acid?

A

a derivative of vitamin A which binds to the disrupted retinic acid receptor and causes blasts to mature into neutrophils - used to treat promyelocytic leukaemia

34
Q

when is arsenic trioxide used?

A

when AML relapses

35
Q

what is the pathophysiology of CML?

A

translocation of chromosomes 9 and 22. the modified chromosome 22 is called the philadelphia chromosome and within it BCR and ABL now sit next to eachother and form the BCR-ABL gene. This forms the BCR-ABL protein which is a tyrosine kinase which causes myeloid cells to divide rapidly, increasing the risk of mutations. As a result of this, cells only partially mature and don’t work effectively so there are too many premature cells accumulated in the vone marrow which enter the blood and crowd out healthy cells

36
Q

what is the pathophysiology of CLL?

A

chromosomal mutations that cause B cells to interfer with B cell receptors and activate tyrosine kinases. This causes prevention of maturation of cells and prevention of cell death. As a result of this, cells only partially mature and don’t work effectively so there are too many premature cells accumulated in the vone marrow which enter the blood and crowd out healthy cells

37
Q

what would CML look like in a blood smear?

A

increased granulocytes and monocytes
normocytic anaemia
normaly-> slightly increased platelet count

38
Q

what would CLL look liike on a bloos smear?

A

smudge cells - broken, immature B cells
normocutic anaemia
small lympjocytes with irregular nuclei and clumped chromatin
normal-> decreased platelets

39
Q

how do we diagnose chronic leukaemia?

A

blood smears
full blood count
genetic testing to look for philadelphia chromosome and chromosomal abnormalities
direct Coombs test
bone marro and lymph node biopsy
scans to check general health
lumbar puncture if risk that its spread to nervous system

40
Q

what is direct Coombs test?

A

checks if CLL cells are making antibodies which can damage the RBCs

41
Q

which leukaemias are philadelphia chromosome positive?

A

chronic myeloid leukaemia

acute lymphoid leukaemia

42
Q

what are the 3 main stages of CLL?

A

stage a - enlarged lymph glands in <3 areas and high WBC count
stage b- enlarged lymph glands in >3 areas and high WBC count
stage C- enlarged lymph glands or enlarged spleen, high WBC count, low RBC/platelet count
note stage b and c need treatment right away

43
Q

how do tyrosine kinase inhibitors work?

A

they bind to the BCR-ABL protein (a tyrosine kinase) which prevents ATP binding and this prevents uncontrolled cell division and induces apoptosis

44
Q

what are examples of tyrosine kinase inhibitors?

A

imatinib
nilotinib
bosutinib

45
Q

what are some side effects of tyrosine kinase inhibitors?

A 
nausea 
vomiting
diarrhea
muscle cramps
bone pain
fatigue
rashes
periorbital oedema and CHF - fluid retention
46
Q

what are autologous stem cell transplants?

A

when stem cells are colected from a patient’s blood and then re-introduced after treatment

47
Q

what is an allogenic stem cell transplant?

A

transferring the stem cells from a healthy person (the donor) to the patient’s body after high-intensity chemotherapy or radiation.

48
Q

what’s a tandem stem cell transplant?

A

2 analogous transplants are performed within a period of no more than 6 months

49
Q

what is a mini stem cell transplant?

A

a modified form of procedure that uses lower, less toxic diseases of chemo/radiation before giving the allogenic transplant.

50
Q

who might be given a mini stem cell transplant?

A

someone who is older, has organ complication, is not healthy or strong enough to undergo standard treatment

51
Q

how does a stem cell transplant work?

A

A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones that can build a new immune system

52
Q

what is a cord blood donation?

A

blood is taken from the placenta and umbilical cord after birth of the baby

53
Q

what are stem cell transplants used for?

A

to treat conditions where the bone marrow is damaged and unable to produce cells e.g. lymphoma, leukemia and multiple myeloma

54
Q

what are the advnaatges of adult stem cell transplant?

A

thought to be less likely to be rejected than embryonic stem cells

55
Q

what are the advanatges of embryonic stem cells over adult stem cells?

A

can be maintained and grow for over a year in culture

ESCs are pluripotent cells so can generate most cell types

56
Q

what are disadvantages to adult stem cells?

A

limitations on differentiation
cannot be grown for a long time in culture
usually in a very small number in each tissue making them difficult to find
currently no technology available to generate large quanities of stem cells in culture

57
Q

what are disadvanatges to embryonic stem cells?

A

these therapies are largely new and much more research and testing is needed
if used directly from the ESC undifferentiated culture prep for tissue transplants they can cause tumours

58
Q

what are some risks of stem cell transplants?

A 
graft-versus-host-disease
anaemia, excessive bleeding/bruising, recurrent infections caused by the chemo/radiation before
graft failure
infertility
cataracts
lung and bone damage
durther caners
early menopause
59
Q

what are some side effects of stem cell transplants?

A 
nausea
vomiting
mouth and throat pain
bleeding
interstitial pneumonia
infections
hepatic veno-occulusive disease
60
Q

how long does it take to recover from a stem cell transplant?

A

3-12 months

61
Q

what is the preparation stage of an autologous stem cell transplant?

A

4-7 daily inections of G-CSF to stimulate stem cell production
these are collected for 2-4 days over several hours from bone marrow or blood stream through apheresis
stem cells are then frozen

62
Q

what is mobilization?

A

When certain drugs are used to cause the movement of stem cells from the bone marrow into the blood.

63
Q

what is the conditioning stage of stem cell transplants?

A

high dose anti-lymphoma treatment before the infusion of stem cells - this usually involves chemotheray or irradiation to make room for new healthy stem cells and prevent rejection

64
Q

outline the stem cell infusion stage of stem cell transplants?

A

1-2 days after conditioning treatment finishes, stem cells are given through a central line over 30-60 minutes

65
Q

why do we get soem side effects from stem cell infusion?

A

from the preservatives used when stem cells are frozen

66
Q

what is the engraftment stage of stem cell transplants?

A

when transplanted stem cells travel through the blood to the bone marrow, where they begin to make new white blood cells, red blood cells, and platelets. It usually happens within 2 to 4 weeks after a stem cell transplant.

67
Q

what needs to be a match for stem cell transplants?

A

human leukocyte antigens

68
Q

who is most likely to have matching HLA with you?

A

siblings

69
Q

what is a match unrelated donor transplant?

A

when you do not have siblings so you randomly match as close as possible to the HLA type

70
Q

what is a haploidentical docnor?

A

a relative whose HLA type half matches

71
Q

what source of stem cells doesn’t need to match as closely to your HLA type?

A

umbilical cord

72
Q

what can stop you from donating stem cells?

A

having an autoimmune condition

73
Q

what is the most common way to give stem cells?

A

through peripheral blood (80% of the time)

74
Q

where is bone marrow removed from surgically?

A

the back of your pelvic bone via two small punctures.

75
Q

what is the recovery time period for after giving stem cells?

A

48 hours in hopsital and up to 5 days recovery.

76
Q

what is the blast crisis?

A

Large clusters of blasts are seen in the bone marrow. The blast cells have spread to tissues and organs beyond the bone marrow. These patients often have fever, poor appetite, and weight loss. In this phase, the CML acts a lot like an acute leukemia.

77
Q

what are the 3 stages of leukaemia?

A

chronic - The blood and bone marrow contain less than 10% blasts.
accelerated - most patients with this phase of CML have 10% -> 19% blasts in both the blood and bone marrow or more than 20% basophils in the peripheral blood.
blast - there are 20% or more blasts in the blood or bone marrow, and it is difficult to control the number of white blood cells.

B9W6 (7 decks)

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