Leukaemia Flashcards
What is leukaemia?
Cancer of haematopoietic cells associated with increased WBC number in bone marrow or blood
4 types of leukaemia
- acute lymphoblastic leukaemia
- acute myeloid leukaemia
- chronic myeloid leukaemia
- chronic lymphocytic leukaemia
How does a haematopoietic stem cell become B and T lymphocytes?
- haematopoietic stem cell
- may become a lymphoid progenitor in the bone marrow
- either becomes a B or T lymphocyte which spill out into peripheral blood
- B lymphocytes will become activated in nearest lymph undergoing germinal centre reaction for specific antigen
- specific B lymphocyte will become a plasma cell
- T cells do cytotoxic cell killing
How does a haematopoietic stem cell become other blood cells?
- HSC becomes a myeloid progenitor cell which will grow and diff. in bone marrow
- these can become mature neutrophils, eosinophils, basophils, monocytes, platelets and red cells leaving marrow and into blood
How do the different types of haematological malignancies arise?
- lymphoid progenitor mutation = ALL (stuck at this stage making lots of these progenitor cells/blasts)
- myeloid progenitor mutation = AML (stuck at this stage again)
- mutation when mature B lymphocyte = CLL
- mutation when lymphocyte in lymph node undergoing germinal centre reaction = lymphoma
- mutation of plasma cells = myeloma
- mutation of matured myeloid progenitors = myeloproliferative disorders
Diagnostic tools for haematological malignancies?
- blood film
- bone marrow biopsy
- flow cytometry
- chromosome abnormalities (G banding and FISH)
- gene point mutations via sequencing
What is flow cytometry?
- immunophenotyping
- looking at antigens on surface of cell
- sometimes cannot see the difference in types of blood cells from microscope morphology so need to see these markers to differentiate
- distinguish cancerous from normal tissue as well as different types of haematological malignancies
- through using antibodies to bind to specific antigens you are searching for
How does G banding work?
- culture cells and stop at metaphase
- colour them and lay them out
- detect chromosomal abnormalities which are present in some haematological malignancies
How does FISH work?
- cells do not need to be in metaphase
- fluorescent probes detect specific DNA sequences/chromosomal translocations/gains/losses of regions in the genome
How is sequencing different from FISH?
- looking at specific DNA sequence changes not larger chromosomal changes
AML and ALL characteristics
- diagnosis
- treatment
- accumulation of undifferentiated blasts in bone marrow
- overwhelm normal blood cells spilling over into peripheral blood
- > 20% blasts in bone marrow or blood to diagnose it
- aggressive/fast growing/ fatal if untreated
- need intensive, high dose, myelosuppressive chemotherapy
- exclude other causes = infections and other malignancies
AML presentation
- low Hb anaemia = tiredness, SOB
- WCC low/neutropenia = fever, pneumonia, fungal infection
- leucostasis = high white cell count so blood is viscous clogging flow in vessels due to overspill = stroke/confusion/SOB/headache
- gum and skin infiltration
- bone pain
- low platelets/thrombocytopenia = bleeding and bruising in GI and cerebral areas
Who is AML common in?
- increasingly frequent in older people
Diagnosis of AML
FBC = low Hb. WCC high or low, low platelets
- renal function (failure?)
- raised urate and LDH
- clotting (APML)
- blood film
- bone marrow biopsy
- immunophenotyping
- cytogenetics
- mutations
Bone marrow biopsy sign of AML
Auer rods
- elongated structures from grouping of granules
AML treatment
- blood transfusion for anaemia
- pit transfusion for thrombocytopenia
- neutropenia = prophylactic antibiotics and neutropenic sepsis treatment immediately with broad spectrum ABs
- look out for tumour lysis=allopurinal/rasburicase fluids
- emergency venesection or leucopharesis for leucostasis
- intensive chemo
- allogeneic stem cell transplant
Why do you get tumour lysis in AML?
- blasts break down releasing toxins
- renal failure, high potassium, high urate, high Ph, low calcium
How do you decide on which treatment to give with AML?
- risk stratified patients
- use cytogenetics and mutations to see the type of mutation they have and compare to graphs showing risk of that specific mutation and chance of survival
Disadvantages of chemotherapy for AML
- affects cells which have high turnover so normal cells like hair, gut, intestinal tract and bone marrow
What is a Hickman line?
Like a cannulae but stay in for weeks to months without changing as need to access blood cells constantly for tests and drugs
- but clots and infections
Types of bone marrow transplant
Auto = give back own stem cells (not much for acute leukaemia) Allo = give back someone elses, must be matched for HLA-antigens
2 types of allogeneic transplants
- myeloblative = wipe of BM completely
- reduced intensity = some chemo to make room in BM for new stem cells
What is the graft-versus-leukaemia effect?
- allows by allogeneic transplant
- get immune reaction from transplanted cells against residual tumour cells
- works like chemo
- however may start attacking normal cells which it does not recognise as self = graft vs host disease
Prognosis for AML
- depends on risk group
- children and young adults 50% long term cure
- over 70 less than 10%
Who is ALL common in?
- commonest childhood cancer
- 2-4 years peaks
ALL presentation
- lethargy, bone pain, anorexia
- neutropenia = infection
- thrombocytopenia = bleeding
- anaemia
- lymphadenopathy = SVC obstruction if mediastinal enlarged nodes
- abdominal organomegaly
- CNS involvement?
ALL diagnosis
same as AML
ALL treatment
Phases
1) remission induction (prednisolone, asparaginase)
2) consolidation (chemotherapeutic agents)
3) CNS directed therapy as can affect CNS more commonly so need to penetrate BBB (high dose methotrexate)
4) maintenance therapy (prednisolone and methotrexate for 2-3 years)
Treatment lasts longer than ALL
Prognosis for ALL
Childhood = more than 95% remission Adults = lower rate, more need allogeneic BM transplant as well as chemo
Difference between chronic and acute
- slower growing
- don’t always require treament
CLL who?
- older 65-70 years
- asymptomatic detected on FBC
presentation of CLL
- symptoms related to anaemia = night sweats, tiredness, weight loss
- thrombocytopenia, lymphadenopathy
- hepatosplenomegaly
- recurrent infections as immunosuppression
CLL diagnosis
- lymphocytosis > 5
- normochromic normocytic anaemia +- autoimmune haemolytic anaemia
- thrombocytopenia
- hypogammaglobulinaemia
- mature lymphocytosis with smear cells on blood film
- immunophenotyping
- if raised WBC count look at types
What is a blood film feature of CLL?
- smear cells which are broken up mature lymphoblastic cells
- small mature lymphocytes
Treatment for CLL and indications
- initially observed
- treatment if = progressive marrow failure, organomegaly, massive LN, systemic symptoms, haemolytic anaemia
- steroids for autoimmune complications
- chlorambucil alkylating agent
- purine analogue fludarabine
- rituximab (anti CD20 mAb)
- combination chemo
- supportive care via transfusion and infection treatment
CML blood count
- increased granulocytes
- eosinophils high
- basophils high
- increased neutrophils in blood
CML presentation
- weight loss, tiredness, night sweats
- splenomegaly
- anaemia
Stages of CML
Chronic 3-5 years
Accelerated 3-6 months (loss of immature blast cells if don’t treat)
Blast crisis 3 months
Death
What is a key marker of CML?
- classic for 9 and 22 chromosome translocation
- forms BCR-ABL protein
Treatment of CML
- imatinib (inhibits BCR-ABL abberant protein), blood count normalises, very effective
- however other cancers more complex so cannot target one protein with them
What is MDS?
Myelodysplastic Syndrome
- dysplasia of blood cells
- HSC problem so produce faulty red cells, neutrophils and platelets
- severe anemia, neutropenia, thrombocytopenia
- need transfusion
- in elderly usually > 65
- blood film, bone marrow biopsy, cytogenetics
- treat infections
- DNA demthylating agent azacytidine
- bone marrow transplant
- can transform to AML!
What other investigations are common with haematological malignancies?
CXR = mediastinal mass or infection Ophthalmoscopy = so no bleeding ECG = before giving cardiotoxic chemo CT Chest Abdo Pelvis = is asses or spleen liver enlargement CSF = if neurological symp
