Haematology - CLL, myelodysplasia Flashcards
CASE HX - CLL
i) name two proteins expressed by B cells that are a signature immunophenotype for CLL?
ii) what staging system is used for CLL?
iii) what are the B symptoms? (3)
iv) what may be seen in relation to WCC, Hb, LN and spleen size in CLL?
v) name an alkylating agent that may be used to treat it? name a nucleoside analog, name a MAB
i) CD5 and CD19+ B cells
ii) Binet stage systen
iii) night sweats, weight loss, fever
iv) rising WCC (look at doubling time), falling Hb, bulky LNs, splenomegaly
v) alkylating - chlorambucil
nucleoside - fludarabine
MAB - rituximab
IBRUTINIB AND CLL
i) what is it?
ii) which chromosome is of interest in CLL? why?
iii) how is ibrutinib given? does it eradicate the disease long term?
iv) name a rare complication and why it may occur? what is given to prevent this?
v) name four side effects of ibrutinib
vi) what may CLL transform to?
i) brutons tyrosine kinase inhibitor
ii) 17p = where p53 is found
iii) orally
iv) pneumonitis/recurrent chest infections due to immmune paresis (low Igs and B cells not working properly)
- give IV immunoglobulin to prevent this
v) hypertension, arrhythmias, bleeding, colitis
vi) lymphoma
VENETOCLAX
i) what does it block? how does this help treat the disease
ii) what can be a consequence of this? name the four features
iii) which patients may it be used in
i) BCL2
- CLL cells often over express BCL2 (pro apop protein) which helps them survive and persist- blocking it causes cell death
- triggers apoptosis of CLL cells
ii) tumour lysis syndrome (high potassium, high phosphatem low calcium and raised creatinine)
iii) patients with 17p deletion of TP53 mut or relapse post first line tx
CLL OVERVIEW
i) by what lymphocyte countt is it defined? which two things are also often enlarged?
ii) what method is used to immunophenotype cells?
iii) what is management determined by? what else caan help determine prognosis?
i) lymphocyte count >5 x109/L
- splenomegaly and lymphadenopathy
ii) flow cytometry
iii) mx det by whether there is p53 mutation or deletion
- Ig variable heavy chain mutation status can also be used to help determine prognosis
CLL TREATMENT
i) when is treatment indicated?
ii) what is first line if p53 WT? what is given if paatient is less fit? (2)
iii) what is first line if p53 mut/relapsed CLL? (3)
iv) what is given if CLL is complicated with autoimm haemolytic anaemia or immune thrombocytopenia purpura?
i) if there is bone marrow failure (cytopenias)
ii) WT P53 > chemo immuno FCR regime
- fludarabine, cyclo, rituximab (anti CD20)
- if patient less fit then give bendamustine/ritux or chlorambucil/obinutuzumab
iii) mut P53/relapsed > use targeted therapy
- ibrutinib (BTK inhibitor)
- venetoclax (oral BCL2 inhibitor)
- idelalisib (oral PI3K inhibitor - B cell receptor signalling protein)
iv) complicated by AIHA etc > give steroids (prednisolone)
CASE HX - MYELOFIBROSIS
i) which organ may be enlarged and therefore palpable?
ii) which blood marker is often very raised?
iii) what does LDH level give an indication of?
iv) what is an leucoerythroblastic blood film?
v) what other cell type may be seen on blood film?
i) spleen
ii) B12
iii) level of LDH can indicate malignant disease burden
iv) lots of immature cells
- erythroblasts (immature nuc RBC) in circ
- myelocytes (immature neuts) in circ
- BM is under stress so pushes out immature cells
v) teardrop red cells
BONE MARROW IN MYELOFIBROSIS
i) will there be lots or little cells on BM aspirate?
ii) what may be seen on BM trephine?
iii) what other early type of cell may be seen?
iv) CD what is a marker of primitive haemato cells and may be seen in increased numbers?
i) lots
ii) reticulin fibrosis
iii) megakaryocytes
iv) CD34
MYELOPROLIFERATIVE DISORDERS - OVERVIEW
i) what are they?
ii) name two conditions that may develop before myelofibrosis?
iii) what goes wrong in essential thrombocytopenia? polycythaemia vera? which organ is massively enlarged in MF?
iv) what type of disorders are they? why?
v) what can myelofibrosis transform to?
vi) name four symptoms of MF
i) spectrum of clinically overlying disease - excess prod of blood cells and precursors/fibrosis of BM
ii) essential thrombocytosis and polycythaemia vera
iii) ET - too many plats > risk of thrombotic complication
PCV - too many red cells
MF - massive spleen
iv) stem cell disorders as affect many lineages
v) AML
vi) fatiguee, itchy, night sweat, bone pain
POLYCYTHAEMIA VERA - SIGNALLING
i) what happens to progenitor cells derived from PV patients in the absence of exog EPO?
ii) name two things that are abnormal about PV progenitors?
iii) which signalling pathway is activated in the cells? which protein mediates this?
iv) which signalling pathway works in all haematopoeitic cells in the BM?
i) they proliferate therefore have autonomous growth
ii) growth factor hypersensitivity and abnormal receptor cytokine signalling
iii) activation of EPO sig transduction pathway
- mediated by JAK2 tyrosine kinase (EPO binds R and phos JAK TK > stat signalling)
iv) JAK STAT
MYELOPROLIFERATIVE DISORDER MUTATIONS
i) which key protein is implicated in PCV? what is the mutation?
ii) what type of mutation is it and what does it lead to?
iii) is it an acquired or inherited mutation? what % of patients with PCV have the mutation?
iv) what two other conditions implicate the same mutated protein?
i) JAK2
- G to T at position 617 = JAK2 V617F
ii) gain of function mutation that leads to consituitive activation of JAK2
iii) acquired (only found in haemato cells)
iv) essential thrombocytopenia (50%) and primary myelofibrosis (50%)
POLYCYTHAEMIA RUBRA VERA
i) how is it confirmed?
ii) how is it managed?
iii) what may also need to be given due to clot risk
i) confirmed by JAK2 mut analysis
ii) managed by regular venesection to maint haematocrit <0.45
iii) give aspirin 75mg daily
ESSENTIAL THROMBOCYTOPENIA
i) how is diagnosis confirmed?
ii) name three things that if negative, allow ruling out of ET
iii) if patient is <60yrs and plats <1500 and no VTE hx - what tx is given?
iv) if patient is >6-, >1500 plats or previous VTE - what tx is given?
i) JAK2 mutation analysis
ii) raised inflammatory makers, infection and inc MKC in BM biopsy
iii) aspirin
iv) aspirin and hydroxycarbamide (brakes on BM to prevent high plats)
RUXOLITINIB
i) what does it inhibit?
ii) name two effects it has on patients?
iii) is this a definitive treatment?
iv) what is one of the limiting problems of use?
v) how does it affect overall survival?
i) inhibits JAK2
ii) reduces spleen size and can improve blood counts
iii) no - most patients become refractory to tx but have improved QOL
iv) rux reduces spleen size - because BM is fibrotic, haematopoiesis is pushed into spleen so reducing spleen size can reduce counts
v) improves OS compared to placebo
CASE HX - MYELOMA
i) what is the key diagnostic test? what will be seen? (2)
ii) what other assay can be used and what is seen?
iii) what is the first line imaging technique for dx?
iv) what can be given for the hypercalcaemia?
v) what may happen to the spine? what can be given to relieve this?
vi) what is the standard first line chemo regime? (4)
i) serum protein electrophoresis
- monoclonal IgA paraprotein and immune paresis (low IgG/M)
ii) serum freelight chain assay
- look at light chain ratio (inc kappa light chain and K:L ratio)
iii) MRI scan - look for cord compression/lytic lesions
iv) pamidronate
v) may get cord compression > give dex
vi) velcade, cyclo, thalidomide, dex
MULTIPLE MYELOMA
i) what is it?
ii) how is the dx confirmed? what is seen?
iii) name four features
i) BM is replaced with plasma cells
- reduced normal haematopoesis
ii) confirmed by BM biopsy - infiltration with plasma cells
iii) acute cord compression, acute renal fail (clogged with light chains > blocks tubules), hypercalcaemia, anaemia
