Haematology - worried midwife Flashcards
ACUTE MYELOID LEUKAEMIA - BLOOD FILM
i) what type of cells will be seen?
ii) name a hallmark of these cells
iii) what nuclear/cyto appearance do these cells have?
iv) why do these cells arise in AML?
v) will WCC be high or low?
i) myeloid blast cells
ii) auer rods - cytoplasmic inclusion bodies
iii) large nuclei and little cytoplasm
iv) there are genetic mutations that block the ability of the myeloid cells from differentiating
v) low as you cant produce normal WCC therefore counts fall
BONE MARROW BIOPSY
i) what two samples are taken?
ii) name three tests the biopsy is sent for and what each tests
iii) name two cell surface markers of AML
iv) name three commonly mutated genes in AML? what does knowing the mutational profile of these genes allow?
i) bone marrow aspirate (liquid from medulla of the bone)
- bone marrow trephine (core of tissue that retains architecture)
ii) send for flow cytometry - look for cell surf markers
- cytogenetics - chromo abnormalities
- molecular analysis - looks for mutations in known AML genes
iii) CD33 and CD117
iv) AML genes = FLT3, NPML, DNMT3A
- knowing these muts allows planning of prognosis and treatment
AML TREATMENT
i) which two drugs are given in the DA chemo regime? what type of drug is each one
ii) name two types of cell that may be given in supportive therapy
iii) name two antibiotics that may be started of neutropenic fever occurs
iv) name the three broad steps in treatment
v) how many cycles of therapy are given?
i) Daunorubucin (anthracycline) and cytarabine (nucleoside analog)
ii) give daily plats and red cell transfusions
iii) tazocin or teicoplanin
iv) chemotherapy - kills rapid dividing cells
supportive - antibiotics, antifungals, transfusions
allogeneic SCT - sibling or unmatched donor
v) 4 cycles - induction + 3 cycles of consolidation
AML PROGRESS AND REMISSION
i) what procedure will be done to check the morphology of cells?
ii) how is minimal residual disease monitored? what does it allow for?
iii) why may stem cell transplant be needed?
iv) what may be done if the patient has iron overload from multiple blood tranfusions?
i) bone marrow biopsy to look at morphology
ii) monitor MRD by flow cytometry
- allows for detection of leuakaemic clones using specific markers
iii) SCT if rising MRD levels are detected
iv) venesection to treat iron overload
AML OVERVIEW
i) what is leukaemia?
ii) what aspects of BM failure cause - fatigue, infections, bleeding?
iii) name four clinical features of AML
iv) name one type of leukaemia that has a good prognosis if treated early? which two mutaations give intermediate risk? which two mutations give poor prognosis?
v) what is the mostt importaantt determinant of AML outcome?
i) uncontrolled proliferation of primitive cells in the bone marrow
ii) fatigue - anaemia
infections - neutropenia
bleeding - thrombocytopenia
iii) anaemia, infections DIC, ulcers, bruising
iv) APML has good prognosis if treated early t 15;19
- intermed risk - DNMT3Aa and NPM1
- poor prognosis - P53, FLT3, monosomy 7
v) age
STEM CELL TRANSPLANT
i) which two ways can stem cells be taken from a donor
ii) which cells are then depleted before introduction to recipient
iii) which two things does the patient have to recieve before they get the donor cells?
iv) name three things the host may need after getting the donor cells
i) bone marrow aspirate or leucophoresis after GCSF injection
ii) T cell depletion
iii) patient get high dose chemo and total body irradiation
iv) host gets intensive support therapy
- red cells and plats
- antibiotics
- prophylaxis against GvHD (cyclosporin and methotrexate)
NEUTROPENIC SEPSIS
i) what is it?
ii) which type of bacteria ar most dangerous? give an example
iii) what two things should be done/given if fever >38
iv) what are first line ABs?
v) is this a medical emergency?
i) when you get an infection with a very low WCC
ii) gram negative - pseudomonas
iii) do blood cultures and give blind AB therapy
iv) tazocin +/- gent
v) yes
GRAFT VS HOST DISEASE
i) what is it caused by?
ii) how many days post transplant does acute become chronic?
iii) name two ways it can be prevented
iv) name threee clinical manifestations
v) what is the graft vs leukaemia effect?
i) caused by donor/host cell mismatches in major and minor HLA loci
ii) acute <100 days and chronic >100 days
iii) prevent by depletion of T cells from the donor cells
- immunosupress the recipient (ciclosporin)
iv) skin rash, diarhoea (bloody), deranged LFTs
v) how the SCT cures leukaemia
DNMT3A MUTATIONS IN AML
i) what are the three most commonly mutated genes in AML?
ii) what is the role of DNMT3A?
i) DNMT3A, FLT3, NMP1
ii) methyltransferase - modifies methylation of DNA and leads to abbherant diffrentiation of cells in AML
ACUTE PROMYELOCYTIC LEUKAEMIA
i) name two features of pro myelocytes
ii) which cell surface marker is common in APML?
iii) which gene rearrangement is a hallmark? how is this confirmed?
iv) what fatal condition are patients with APML at risk of?
i) granules and folded nucleus
ii) CD34
iii) PML-RARA (15;17 transloc)
- confirmed by real time PCR
iv) DIX due to deranged coagulation/clotting
APML TREATMENT
i) what is the mainstay of treatment? what does it do?
ii) when should the treatment be given after diagnosis?
iii) what syndrome can occur with this treatment in 15% of patients? which cells are seen in high numbers? name three symptoms
iv) how is the above syndrome treated?
v) name another treatment that can be given and how it works
vi) which organ needs monitoring due to this combo treatment?
i) ATRA (all trans retinoic acid)
- acid form of vit A > binds to RA receptor alpha (RARA)
- induces terminal differentiation of promyelocytes
ii) should be given as soon as APML is diagnosed
iii) can get ATRA syndrome/differentiation syndrome
- see high WCC
- dyspnoea, fever, weight gain, oedema
iv) treat with steroids (dex) and withdrawal of ATRA
v) arsenic trioxide
- degrades PML RARA fusion protein and induces apoptosis of promyelocytes
vi) treatment can cause QT prolongation > heart monitoring
APML OVERVIEW
i) what is it?
ii) what is it typically complicated with at presentation? does it present in the young or old?
iii) when is the highest risk of mortality? what is the overall 10 year survival?
i) malignant proliferation of promyelocytes
ii) usually complicated with DIC at presentation
- caused by releease of pro coag material
- usually presents young
iii) highest risk of mortality is early in disease due to haemmorhage
- overall 10 yr survival is 80-90%
GENETIC MUTATIONS IN APML
i) between which two chromos is there a translocation in 95% of cases?
ii) by which analysis method is the mutation detected?
iii) which two genes are involved in the translocation and what is the role of each?
iv) what does the new fusion protein do? name three types of cells that are therefore present in the blood/bone marrow
i) transloc between 15 and 17
ii) ident by FISH or cytogenetic analysis
iii) juxtaposition of PML and RARA genes
- PML - promyelocytic leukaemia gene
- RARA - retinoic acid receptor alpha gene
iv) fusion protein prevents transcription and blocks granulocyte differentiattion
- see promyelocytes, blast cells and auer rods in films
THE FUTURE OF APML
i) is chemo or ATRA-arsenic combo more effective treatment?
ii) name two ways early mortality can be reduced
iii) what is long term survival with targeted therapy?
i) ATRA-arsenic (non chemo tx)
ii) vigorous blood product support and early admin of ATRA
iii) LT survival 90%
CHRONIC MYELOID LEUKAEMIA
i) name two symptoms (non spec)
ii) what may be seen O/E? (2)
iii) what may be seen on blood film
i) fatigue and abdo distention
ii) massive splenomegaly
- retinal haemmorhage
iii) myeloid cells at all stages of maturation
