Acute Lymphoblastic Anaemia Flashcards
What is Leukaemia?
- Leukaemia refers to a group of malignancies that arise in the bone marrow
How common is Acute lymphoblastic leukaemia?
- most common malignancy in children
How does acute lymphoblastic leukaemia arise?
- ALL arises from a clone of lymphoid progenitor cells that undergo malignant transformation
- Most are B cell in origin
- As clonal expansion occurs lymphoid precursors replace other haematopoietic cells in the bone marrow
What is the peak age for ALL ? What gender is more commonly affected?
It is the most common under 5s. More common in males
What are the risk factors for ALL?
- Genetic Conditions
- Previous treatment with chemotherapy (etoposide, thiotepa, busulfan)
- Ionising Radiation Exposure (atomic bomb exposure, Chernobyl nuclear power plant, CT scan and Radiotherapy)
- Exposure to Benzene (petrol industry, chemical industry, rubber industry and shoe production)
- Weakened immune system
Where can leukaemia spread to?
- lymph nodes
- liver
- spleen
- CNS
- testicles
Which cells are affected in ALL?
- B lymphocytes
- T lymphocytes
What are the types of ALL?
- B-cell Acute lymphoblastic leukaemia ( precursor B cell ALL, mature B cell ALL, Common ALL, Pro B cell ALL)
- T cell Acute lymphoblastic leukaemia
- Philadelphia Positive ALL
What happens in Philadelphia positive ALL?
- There is a change in the chromosome of the leukaemia cells
- The ABL1 gene on chromosome 9 breaks off and sticks to the BCR gene on chromosome 22
- This produces a BCR-ABL1 gene which causes the cell to make too much of the protein tyrosine kinase
- This protein causes leukaemia to grow and multiply
How is Philadelphia positive ALL treated?
- Imatinib
How and why does leukaemia affect you?
- Many abnormal WCC are produced, hence you are more likely to get infections and may find it more difficult to get rid of them
- Lower amount of RCC and platelets due to the overcrowding of the WCC
- Low RCC causes anaemia leaving you feeling tired and breathless
- Low Platelets Leads to bleeding problems such as nosebleeds
What are the symptoms of ALL?
- General Weakness
- Feeling Tired
- High Temperature
- Frequent Infections
- Bruising/ Bleeding easily (nosebleeds, heavy periods, bleeding gums, blood in urine/stool)
- Weight Loss
- Swollen Lymph Nodes
- Feeling SOB
- Feeling Full in tummy
- Pain in bones or joints
- Pale skin
Which symptoms of T cell ALL can be life threatening?
- Swollen lymph nodes in the centre of your chest OR thymus gland is bigger in the upper chest.
- This presses on the windpipe causing breathlessness and coughing
- Pressure on the vessels going to the head causing SVCO
What blood tests would you want to investigate for ALL? What would you see on a blood film?
- FBC ( anaemia, thrombocytopenia, leucocytosis with neutropenia)
- U+E ( Hypercalcaemia due to release of PTH-like hormone)
- LFTs
- Clotting and D-Dimer ( risk of DIC)
- Uric Acid and LDH (non specific markers of tumour burden
- BLOOD FILM = BLAST CELLS
- Blood Borne Virus Screen (HIV, HBV, HCV, EBV, CMV)
What Imaging would be done?
- CXR ( would show mediastinal mass)
- CT CAP ( lymphadenopathy and organ involvement)
- CT/ MRI head (patients with symptoms indicative of neurological involvement)
What is the definitive diagnostic tool?
- Bone marrow aspiration and biopsy
What specialist blood tests can be done on the bone marrow biopsy?
- Immunophenotyping- determines whether ALL or AML and the subtype either B cell or T cell
- Flow Cytometry
- FISH ( fluorescence in situ hybridisation) - this is a test which looks at chromosome changes in cells it can help your doctor decide which treatment is best for you
- PCR ( Polymerase Chain Reaction) - a test to pick up changes in genes and chromosomes to help diagnose cancer
What other tests can you do ?
- A blood film
- Pleural Tap if there is a pleural effusion
- LP if concern over CNS involvement
What factors indicate a poorer prognosis?
- Worsening age
- Performance Status >1
- WCC - >30 for B cell ALL, > 100 for Tcell ALL
- Cytogenetics - Philadelphia chromosome
- Immunophenotype ( pro B / mature T )
- CNS involvement
- Male Sex
- Non- Causcasian
What is the management of ALL?
- Pre-phase and supportive therapy
- Induction Chemotherapy
- Maintenance Therapy
- Stem cell Transplant
- Palliative Care
What is the Pre-Phase and Supportive Treatment?
- Pre-Phase Therapy: patients may be commenced on steroids with allopurinol and IV hydration, this reduces the risk of TLS
- Leucopheresis: used to reduce the WCC
- Supportive therapy: Anaemia + Thrombocytopenia require treatment and G-CSF can be given to increase neutrophils
What is Induction Chemotherapy?
- The aim is to achieve complete remission or Molecular complete remission
What is the definition of Complete Remission?
- Leukaemia not seen in the bone marrow, peripheral blood or CSF
What is the definition of Molecular Complete Remission?
- Everything with Complete Remission plus minimal residual disease not detectable by sensitive molecular probe
What is the Maintenance Therapy?
- Aim is to reduce risk of recurrence
- Regimens include daily 6- MAP ( inhibits DNA/ RNA synthesis) and weekly methotrexate ( inhibits folate in the DNA synthesis via DHRF)
What are the complication of ALL and it’s treatment?
- TLS (tumour lysis syndrome)
- Neutropenic Sepsis
- SVCO
- Chemotherapy side-effects
What is a Bone Marrow Biopsy?
- This is usually taken from the iliac crest
- This involves a local anaesthetic and a specialist needle
- Samples from the bone marrow aspiration can be examined straight away however a trephine sample requires a few days
What are the two types of Bone Marrow Biopsy ?
- Bone Marrow Aspiration
- Bone Marrow Trephine Biopsy
What is a Bone Marrow Aspiration?
- Involves taking a liquid sample full of cells within the bone marrow
What is a Bone Marrow Trephine?
- Involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure
What is tissue typing?
- HLA typing ( Human Leucocyte Antigen)
- Done via a blood test, buccal swab, saliva sample
- Eaxh person has their own set of HLA proteins the doctors check for 10 HLA markers and then compare this to the HLA markers of the donor, you are aiming for a 9/10 or 10/10 match
