Leukaemia Flashcards
What is leukaemia?
A malignant proliferation of haemopoietic stem cells.
Name 4 sub-types of leukaemia.
- AML - acute myeloid leukaemia.
- CML - chronic myeloid leukaemia.
- ALL - acute lymphoblastic leukaemia.
- CLL - chronic lymphoblastic leukaemia.
Give 3 environmental causes of leukaemia.
- Radiation exposure.
- Chemicals e.g. benzene compounds.
- Drugs.
Give 5 symptoms of leukaemia.
- Anaemia.
- Infection and neutropenia
- Bleeding.
- Hepatomegaly.
- Splenomegaly.
Give 5 signs of leukaemia.
- Pallor, fatigue
- SOB
- Angina
- Claudication
- Infections and Fever
- Mouth ulcers
- Bleeding under the skin
- Bruising and Petechiae
Why are hepatomegaly and splenomoegaly symptoms of leukaemia?
Because of tissue infiltration.
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure.
What investigations might you do on someone who you suspect has leukaemia?
- Blood film.
- Bone marrow biopsy.
- Lymph node biopsy.
- Immunophenotyping.
- Cytogenetics.
What is acute myeloid leukaemia (AML)?
Neoplastic proliferation of blast cells derived from marrow myeloid – Myeloblasts (gives rise to basophils, neutrophils and eosinophils) elements
What can increase the risk of developing AML?
Give 3 risk factors.
- Preceding haematological disorders - can be a transformation from a myeloproliferative disorder.
- Prior chemotherapy.
- Exposure to ionising radiation.
- Age.
- Down Syndrome.
What is the typical age of onset of AML?
Around 65
Most common adult leukaemia.
5yr survival 25%
What cell lines are affected in acute myeloid leukaemia (AML)?
Blast cells.
Clonal expansion of myeloid blasts in the bone marrow, peripheral blood or extramedullary tissue.
Unable to differentiate into neutrophils.
List some conditions/RFs associated with AML
Myelodysplastic syndrome (MDS).
Down Syndrome.
Bone marrow failure syndromes (e.g. Fanconi, Diamon-Blackfan, aplastic anaemia)
Smoking.
What is the state of RBC, WBC and platelets in leukaemia?
- Anaemia – low Hb
- Neutropenia – low WCC
- Thrombocytopenia – low platelets
How would you diagnose AML?
- Full blood count – initial 1st line investigation
- WCC usually high
- Neutropenia, Thrombocytopenia, Anaemia - Blood film
- Blast cells, Auer rods - Blood coagulation tests
- Elevated PT time (prothrombin time)
- Normal fibrinogen and D-dimer - Bone marrow biopsy – definitive investigation for diagnosis!!
- Auer rods, hypercellularity
- Aspirate biopsy (>20% myeloblasts = diagnostic) - Imaging – CXR, CT, MRI, PET scanning
- CXR pulmonary infiltrates - Immunophenotyping – cell markers – myeloid? lymphoid? B-cell? T-cell?
- Molecular methods
Which investigation is the definitive test for AML? And what does it find for positive AML?
Bone marrow biopsy – definitive investigation for diagnosis
- Auer rods, hypercellularity
- Aspirate biopsy (>20% myeloblasts = diagnostic)
Treatment for AML: briefly list the 3 methods of AML management.
- Supportive care.
- Chemotherapy: curative v palliative.
- Bone marrow transplant.
How would you manage/treat AML?
Supportive care:
1. IV fluids for hydration
- Hickman line -> easily take bloods for testing, administer
drugs + fluids
- Prophylactic antivirals, antibacterials and antifungals
- Deadly infections caused by neutropenia
- E.G. acyclovir, fluconazole, ciprofloxacin, co-trimoxazole - Blood + platelet transfusions, as needed
- Allopurinol
- Prevent tumour lysis syndrome - Leukoreduction
- Hydroxycarbamide/leukapheresis
Chemotherapy – Induction:
1. Cytarabine + an anthracycline (daunorubicin)
- All-trans retinoic acid added in APML
Stem cell bone marrow transplant.
What drugs can be used in chemotherapy for AML?
- Cytarabine + an anthracycline (daunorubicin)
- All-trans retinoic acid added in APML cancer
Give the main complication of AML.
- Infection is a major issue - be alert to septicaemia.
Causes common organisms to present oddly, with few antibodies being made.
What is CML?
Chronic myeloid leukaemia.
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils) in the BM.
What cell lines are affected in CML?
Myeloid - uncontrolled proliferation of myeloid cells in BM.
What would the FBC from someone with CML look like?
High WBC’s.
What chromosome is present in >80% of people with CML?
Philadelphia chromosome.
Explain why the Philadelphia chromosome causes CML.
Philadelphia chromosome leads to a fusion gene that has tyrosine kinase activity and enhanced phosphorylating activity -> altered cell growth.
What are the genetics/pathophysiology behind CML?
Philadelphia chromosome - translocation between chromosomes 9 and 22 - t(9;22).
1) Ph chromosome produced BCR-ABLE fusion oncogene
2) Produces p210 BCR-ABL protein
3) Expressive active tyrosine kinase on surface of myeloid cells
4) Unregulated cell division
Pathophysiology of CML: how many phases of CML are there?
3 typical phases: the chronic phase, the accelerated phase and the blast phase.
Pathophysiology of CML: describe the chronic phase of CML.
The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised WCC.
Pathophysiology of CML: describe the accelerated phase of CML.
The accelerated phase occurs where the abnormal blast cells take up a high proportion of the cells in the BM and blood (10-20%). In the accelerated phase, patients become more symptomatic, develop anaemia + thrombocytopenia and become immunocompromised.
Pathophysiology of CML: describe the blast phase of CML.
The blast phase follows the accelerated phase and involves an even high proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.
Describe the clinical features of CML
1/3 asymptomatic at presentation.
early symps - weight loss, malaise, fever, night sweats, abdo discomfort (due to splenomegaly), arthralgia (increased uric acid from cell turnover)
in 10% the chronic phase will turn into a symptomatic accelerated phase, or blast phase (AML).
What investigations would you do in CML?
What results would you expect to see?
- Full blood count – initial 1st line investigation
- Very high WCC - with whole spectrum of myeloid cells i.e. increased; neutrophils, myelocytes, basophils and eosinophils
- Anaemia - Low Hb (normochromic and normocytic)
- Platelets are low, normal or raised - BM aspiration biopsy
- Granulocytic hyperplasia – hypercellular - Cytogenetic analysis – FISH
- Presence of Philadelphia chromosome
How would you treat CML?
- Chronic/accelerated phase:
o Tyrosine kinase inhibitors (imatinib) - SEs = muscle cramps/HF.
o May be combined with IFN-α, if required
o High-dose induction chemo and allogenic stem cell transplant, if above fails - Blast phase:
o Tyrosine kinase inhibitor + high dose chemo followed by stem cell transplantation
o May have pancytopenia, requiring blood and platelet transfusion
o Death imminent if this does not work
What is the main medication for CML treatment?
Tyrasine kinase inhibitors.
What is ALL?
Acute lymphoid leukaemia.
Malignancy of immature lymphoid precursor cells (gives rise to T cells and B cells).
What cell lines are affected in ALL?
Lymphoblasts - B/T cell precursors. lymphoid cells replace haematopoietic cells.
Name a trigger of ALL.
Ionising radiation during pregnancy.
Is ALL more common in adults or children?
ALL is mainly a childhood disease.
Describe the pathophysiology of ALL.
- Malignant change in lymphoblast (lymphoid precursor cell – I.E. precursor for B or T cells)
- Promotes uncontrolled, rapid proliferation of immature lymphoblasts in the BM
- Affects a single type of lymphocyte (either T or B lymphocyte cell lines)
- Causes acute proliferation of a single type of lymphocyte
- Excessive proliferation of these cells causes them to replace the other cell types being created in the BM, leading to a pancytopenia.
- Majority of cases derive from B-cell precursors
- If all B cells = CHILDREN
- If all T cells = Adults
Give 4 symptoms of ALL.
- Bone pain.
- Recurrent infections (neutropenia).
- Pale and tired (anaemia).
- Bruising and bleeding (low platelets).
- Swollen testicles.
- Cranial nerve palsies and neck stiffness.
What CNS involvement can you get in ALL?
CNS infiltration by leukaemoid cells presents as papilloedema, nuchal rigidity and meningism.
Also might get focal neurology CN 3, 4, 6, 7
Outline 3 classification systems used in ALL.
FAB (french/american/british):
- L1 - small homogenous blasts (children)
- L2 - large heterogenous blasts (adults)
- L3 - Burkitt large basophilic B cells with vacuoles
Immunological - uses surface markers
Cytogenetic - chromosomal analysis, Ph chromosome is a poor prognosis.
What infections are commonly seen in ALL patients?
CMV, measles, candidiasis, Pneumocystis pneumonia (PCP)
What investigations would you carry out on an ALL patient?
What would the results show?
- History
- Examination
- Full blood count – initial 1st line investigation
- WCC usually high - Blood film
- Blast cells on film + in BM - Bone marrow biopsy – definitive investigation for diagnosis!!
- Aspirate and trephine - Imaging – CXR, CT, MRI, PET scanning
- CXR and CT scan to look for mediastinal and abdominal lymphadenopathy - Lumbar puncture
- To look for CNS involvement - Immunophenotyping – cell markers – myeloid? lymphoid? B-cell? T-cell?
- Cytogenetics/FISH
- Molecular studies
List the 2 treatment options for ALL.
CNS directed therapy and stem cell transplant.
How would you treat ALL?
Supportive care:
1. Prophylactic antivirals, antibacterials and antifungals
- Deadly infections caused by neutropenia
- E.G. acyclovir, fluconazole, ciprofloxacin, co-trimoxazole
2. IV fluids for hydration
- Hickman line -> easily take bloods for testing, administer drugs + fluids
3. Blood + platelet transfusions
4. Allopurinol
- Prevent tumour lysis syndrome
Chemotherapy – CNS directed therapy:
1. Prednisolone, vincristine, daunorubicin + tyrosine kinase inhibitor (imatinib)
2. Intrathecal methotrexate (for CNS disease)
Stem cell bone marrow transplant
Consolidate remission (weeks).
Maintain remission (years).
- Mercaptopurine daily, MTX weekly, vincristine + pred monthly.
List some potential complications of ALL.
- Tumour lysis syndrome
- Neutropenic sepsis
- Pancytopenia
- Chemotherapy SEs
What is CLL?
Chronic lymphoid leukaemia.
Chronic proliferation of a single-type of well-differentiated lymphocyte, usually B lymphocytes, which leads to the accumulation of mature B-cells that have escaped apoptosis.
Who does CLL affect?
What is the prognosis like?
An incurable disease of older people - but some show no/slow progression - have a near normal life expectancy.
(others show active progression so have a worse prognosis).
Most common leukaemia.
What cell lines are affected in CLL?
Mature B cells - they have escaped apoptosis.
What can trigger CLL?
Pneumonia
Name 3 risk factors for CLL.
- Male sex
- Genetics – Mutations, trisomies and deletions influence risk
- Pneumonia may be a triggering event
Give some clinical features of CLL.
- Often asymptomatic (can present as a surprise on routine FBC)
- May be anaemic (due to haemolysis or marrow infiltration)
- Infection prone
- Bleeding
- If severe, then weight loss, sweats and anorexia
- Hepatosplenomegaly
- Enlarged, rubbery, non-tender nodes
- Painless, rubbery lymphadenopathy
How would you investigate CLL?
- Full blood count – initial 1st line investigation
- Normal or low Hb + platelets
- Raised WCC with very high lymphocytes (lymphocytosis) - Blood film
- Smudge cells / Smear cells may be seen in vitro
- These occur during the process of preparing the blood film where aged or fragile WBCs rupture and leave a smudge on the film. - Flow cytometry
- CD5, CD19, CD23 positive - CT scan
- Hepatosplenomegaly, retroperitoneal/mediastinal lymph nodes
Outline staging of CLL and how it influences treatment plans.
Binet:
- A: <3 nodes + normal Hb and Pt
- B: >=3 nodes + normal Hb and Pt
- C: anaemia/thrombocytopenia + any nodes.
Rx:
A+B+asymptomatic = watch and wait, monitor FBC, flow cytometry every 3/12
C = chemo - rtirxuimab + cyclophosphamide + fludarabide +/- stem cell transplant
What is the treatment for CLL?
- Do nothing.
- Blood transfusions.
- Human IV immunoglobulins
- Chemotherapy or Radiotherapy
- mAb.
- Bone marrow / stem cell transplant.
What are 2 main complications to worry about in CLL?
1) Hypogammaglobulinaemia.
= Lymphocytes don’t work = no antibodies - so patient is deficient in IgG/A/M = increased infection risk.
- May need monthly IVIG
2) Autoimmune haemolytic anaemia.
= Dysfunctional antibodies directed towards RBCs.
- Give prednisolone.
For CLL, what is the prognosis rule?
Rule of 3’s:
* 1/3 will never progress
* 1/3 progress slowly
* 1/3 progress actively
Give some clinical features of acute leukaemias.
Marrow failure - anaemia symptoms, infections e.g. candida (neutropaenia), bleeding/petechial rash (thrombocytopaenia).
Circulating cell symptoms - headache, CNS involvement (cranial nerves). Infiltration: skin/gums (some AMLs), hepatosplenomegaly, lymphadenopathy, testicular enlargement.
Tumour related symptoms - bone pain, fever, lethargy and fatigue, night sweats, weight loss.
Which leukaemia most commonly affects children?
ALL - acute lymphoblastic leukaemia
Rare in adults (75% is under <6yrs old). two spikes again in mid 30s and mid 80s
90% will have complete remission (if <30yo)
Which of the leukaemias doesn’t cause recurrent infections?
CML - chronic myeloid leukaemia
Which leukaemia commonly affects the elderly?
CML
Which of the leukaemias is most associated with Down’s syndrome?
ALL - acute lymphoblastic leukaemia
If you see blast cells on a blood film, what does this suggest?
An acute leukaemia
If Auer rods are seen on a blood film, which leukaemia is this?
AML
If smudge cells are seen on a blood film, which leukaemia is this?
CLL
