PBL 1 Flashcards
what are the 4 main types of leukaemia?
acute lymphoblastic
acute myeloid
chromic lymphocytic
chronic myeloid
what types of leukaemia is most common in children?
acute lymphoblastic
what are the 2 types of acute lymphoblastic anaemia?
T-cell ALL and B-cell ALL
which lymphoid cells does chronic lymphocytic leukaemia affect?
B cells
what do haematopoetic stem cells give rise to?
myeloblasts and lymphoblasts
what do myeloblasts give rise to?
erythrocytes, thrombocytes, monocytes, granulocytes
what do lymphoblasts give rise to?
pre-B cells, pre-T cells and natural killer cells
what are leukocyte examples?
neutrophil basophil eosinophil B lymphocyte NK cell T lymphcyte monocytes macrophages
outline the cause of ALL?
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
what are the symptoms of ALL and AML?
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
outline the pathophysiology of AML?
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
what does the FLT3 gene code for?
A protein called FLT3 that helps white blood cells grow.
what hapens if we get a mutation in FLT3?
the growth of too many abnormal leukemia cells. which can be a cause of acute myeloid leukaemia
outline the classification of AML?
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
what is AML with maturation?
> 20% blasts in the bone marrow or blood and evidence of maturation to more mature neutrophils
what is AML wihtout maturation?
a high percentage of blasts in the bone marrow without significant evidence of myeloid maturation.
what is acute promyelocytic leukaemia?
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.
what is acute myelomonocytic leukaemia?
a rare type of AML in which there is an increased production of immature neutrophil and monocytes in the bone marrow.
what is acute monocytic leukaemia?
a subtype of AML, in which >80% of the affected blood cells are a type of white blood cell called monocytes
what is acute erythroid leukaemia?
a rare form of acute myeloid leukemia where the myeloproliferation is of erythroblastic precursors
what is acute megakaryoblastic leukaemia?
a rare form of acute myeloid leukemia (AML), which is characterized by proliferation of ≥20% megakaryoblasts
whats the pathophysiology of acute promyelocytic leukaemia?
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
what are the risk fcators for acute leukaemia?
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
what will a peripheral blood smear look like in AML?
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
what will a peripheral blood stain for ALL look like
lymphoblasts will be large cells with round-oval nucleus, clumped chromatin
normocytic anaemia
>20% lymphoblasts
thrombocytopenia
how do we diagnose acute leukaemia?
peripheral blood smear bone marrow biopsy lymph node biopsy immunophenotyping G-banding FISH PCR
what is immunophenotyping?
uses antibodies to identify cells based on the types of antigens or markers on the surface of the cells.
what is G-banding?
The banding pattern can distinguish chromosomal abnormalities or structural rearrangements, such as translocations, deletions, insertions, and inversions.
what is FISH?
fluorescence in situ hybridization
looks for a small number of specific changes in genes or chromosomes
what are the subtypes of ALL?
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
what are the treatment options for acute leukaemia?
chemotherapy e.g. vincristine regular blood transfusions antibiotics biological therapy stem cell transplants bone marrow transplants radiotherapy all-trans-retinoic acid arsenic trioxide
what are the 2 stages for treating acute leukaemia?
induction - treatment aims to kill as many leukaemia cells as possible
consolidation - treatment aims to prevent relapse
what is All-Trans-Retinoic acid?
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
when is arsenic trioxide used?
when AML relapses
what is the pathophysiology of CML?
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
what is the pathophysiology of CLL?
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
what would CML look like in a blood smear?
increased granulocytes and monocytes
normocytic anaemia
normaly-> slightly increased platelet count
what would CLL look liike on a bloos smear?
smudge cells - broken, immature B cells
normocutic anaemia
small lympjocytes with irregular nuclei and clumped chromatin
normal-> decreased platelets
how do we diagnose chronic leukaemia?
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
what is direct Coombs test?
checks if CLL cells are making antibodies which can damage the RBCs
which leukaemias are philadelphia chromosome positive?
chronic myeloid leukaemia
acute lymphoid leukaemia
what are the 3 main stages of CLL?
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
how do tyrosine kinase inhibitors work?
they bind to the BCR-ABL protein (a tyrosine kinase) which prevents ATP binding and this prevents uncontrolled cell division and induces apoptosis
what are examples of tyrosine kinase inhibitors?
imatinib
nilotinib
bosutinib
what are some side effects of tyrosine kinase inhibitors?
nausea vomiting diarrhea muscle cramps bone pain fatigue rashes periorbital oedema and CHF - fluid retention
what are autologous stem cell transplants?
when stem cells are colected from a patient’s blood and then re-introduced after treatment
what is an allogenic stem cell transplant?
transferring the stem cells from a healthy person (the donor) to the patient’s body after high-intensity chemotherapy or radiation.
what’s a tandem stem cell transplant?
2 analogous transplants are performed within a period of no more than 6 months
what is a mini stem cell transplant?
a modified form of procedure that uses lower, less toxic diseases of chemo/radiation before giving the allogenic transplant.
who might be given a mini stem cell transplant?
someone who is older, has organ complication, is not healthy or strong enough to undergo standard treatment
how does a stem cell transplant work?
A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones that can build a new immune system
what is a cord blood donation?
blood is taken from the placenta and umbilical cord after birth of the baby
what are stem cell transplants used for?
to treat conditions where the bone marrow is damaged and unable to produce cells e.g. lymphoma, leukemia and multiple myeloma
what are the advnaatges of adult stem cell transplant?
thought to be less likely to be rejected than embryonic stem cells
what are the advanatges of embryonic stem cells over adult stem cells?
can be maintained and grow for over a year in culture
ESCs are pluripotent cells so can generate most cell types
what are disadvantages to adult stem cells?
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
what are disadvanatges to embryonic stem cells?
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
what are some risks of stem cell transplants?
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
what are some side effects of stem cell transplants?
nausea vomiting mouth and throat pain bleeding interstitial pneumonia infections hepatic veno-occulusive disease
how long does it take to recover from a stem cell transplant?
3-12 months
what is the preparation stage of an autologous stem cell transplant?
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
what is mobilization?
When certain drugs are used to cause the movement of stem cells from the bone marrow into the blood.
what is the conditioning stage of stem cell transplants?
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
outline the stem cell infusion stage of stem cell transplants?
1-2 days after conditioning treatment finishes, stem cells are given through a central line over 30-60 minutes
why do we get soem side effects from stem cell infusion?
from the preservatives used when stem cells are frozen
what is the engraftment stage of stem cell transplants?
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.
what needs to be a match for stem cell transplants?
human leukocyte antigens
who is most likely to have matching HLA with you?
siblings
what is a match unrelated donor transplant?
when you do not have siblings so you randomly match as close as possible to the HLA type
what is a haploidentical docnor?
a relative whose HLA type half matches
what source of stem cells doesn’t need to match as closely to your HLA type?
umbilical cord
what can stop you from donating stem cells?
having an autoimmune condition
what is the most common way to give stem cells?
through peripheral blood (80% of the time)
where is bone marrow removed from surgically?
the back of your pelvic bone via two small punctures.
what is the recovery time period for after giving stem cells?
48 hours in hopsital and up to 5 days recovery.
what is the blast crisis?
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.
what are the 3 stages of leukaemia?
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.
