Acute lymphoblastic leukaemia (ALL) Flashcards
What is ALL?
Malignant disease of primitive lymphoid cells (lymphoblasts)
Aetiology of ALL?
- Most common childhood cancer, peaks around 2-4 years.
- Can also affects adults over 45 years old.
- Often associated with Down syndrome.
- Associated with the Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL.
Pathophysiology of ALL?
- Occurs when there is a malignant change in one of the lymphocyte precursor cells.
- It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes.
- Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia (significant reduction in all blood cells).
Clinical features of ALL?
- Marrow failure – anaemia, infections and bleeding.
- Leukemic effects – high count with obstruction of circulation, involvement of areas outside the marrow and blood (extra-medullary) e.g. CNS, testis.
- Bone pain
Blood test investigations for ALL?
Bloods:
- Blood count and film: reduction in normal cells, presence of abnormal cells (“blasts”) - large size, high nuclear : cytoplasmic ratio, prominent nucleolus.
- High nuclear : cytoplasmic ratio means a larger than normal nucleus. Present in the blast cells, decreases when cell matures to lymphocyte
- Coagulation screen
Management of ALL?
Multi-agent chemotherapy - can last up to 2-3 years
- Different phases of treatment of varying intensity.
- Targeted treatments in certain subsets.
- Hickman line used to provide long-term central venous access.
Complications of ALL?
Anaemia
Neutropenia (low neutrophil count)
- Increased severity and duration of infections.
- Gram negative bacteria can cause fulminant life-threatening sepsis in neutropenic patients.
- Patients also susceptible to fungal infections.
Thrombocytopenia (low platelet count)
- Bleeding – purpura, petechiae (small bruising under skin)
Complications of ALL treatment?
Nausea and vomiting
Hair loss
Liver, renal dysfunction
Tumour lysis syndrome (during first course of treatment)
Infection
- Bacterial: empirical treatment with broad spectrum antibiotics (particularly covering gram negatives) as soon as neutropenic fever.
- Fungal: if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents.
What are some late adverse effects of ALL treatment?
loss of fertility, cardiomyopathy with anthracycline antibiotics (used in cancer chemotherapy)
What is trephine?
A bone marrow trephine biopsy means they remove a very thin 1 or 2cm long core of bone marrow in one piece.
What is immunophenotyping?
Immunophenotyping is a test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B lymphocytes or the T lymphocytes.
The process identifies cells based on the types of antigens or markers on the surface of the cell.
What is molecular genetics in haematology?
A lab method that uses a sample of tissue, blood, or other body fluid to check for certain genes, proteins, or other molecules that may be a sign of a disease or condition, such as cancer.
Can be used to potentially establish a diagnosis and can be used to assess prognostic significance.
Bone marrow aspirate investigations for ALL?
Bone marrow aspirate:
- Morphology
- Immunophenotype
- Cyto/molecular genetics - diagnostic utility, prognostic significance.
- Trephine - enables better assessment of cellularity and is helpful when aspirate is sub-optimal.
Definition of an acute leukaemia?
- By definition an acute leukaemia involves excess of “blasts” (>/=20%) in either the peripheral blood or bone marrow.
What is tumour lysis syndrome?
The tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy
Characteristic features of tumour lysis syndrome?
Leading to the characteristic findings of:
hyperuricemia (high uric acid in blood)
hyperkalemia (high potassium in blood)
hyperphosphatemia (high phosphate in blood)
hypocalcemia (low calcium in blood)
What are the key features of each of the leukaemia types?
ALL is the most common leukaemia in children and is associated with Down syndrome
CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells
CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome
AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods
How does tumour lysis syndrome (TLS) occur?
It is a potentially life threatening complication that can occur from treatment of rapidly dividing malignancies.
Electrolyte features of tumour lysis syndrome (TLS)?
Hyperkalaemia
Hyperuricaemia
Hyperphosphataemia
Hypocalcaemia - due to high phosphate
What is the management goal for treatment of TLS?
Main goal of management is to prevent renal failure and other complications from high levels of uric acid, potassium and phosphate.
Initial therapy = aggressive hydration and allopurinol
