Acute Lymphoblastic Leukaemia Flashcards
What is acute lymphoblastic leukaemia?
https://www.youtube.com/watch?v=itkRVTqfPsE
Malignancy of lymphoid cells, affecting T or B cell lines, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration
What are known causes of ALL?
Precise cause unknown
- Prenatal Ionizing radiation
- In utero exposure to infection
- Environmental radiation
- Down’s Syndrome
Who does ALL most commonly affect?
Children - rare in adults
What proportion of ALL are of B-cell lineage?
75-90%
How does ALL present?
- Fatigue
- Anorexia
- Fever
- Bone pain
- Painless lumps - Neck, axilla, groin
- Marrow failure - Pallor (anaemia), Infection, Bleeding
- Infiltration - Hepatosplenomegaly, lymphadenopathy, orchidomegaly, CNS involvement
What are signs of thrombocytopenic bleeding?
- Petechiae/Purpura
- Mucosal bleeding - gums
- Fundal haemorrhage
What are the commonest infections that occur in ALL?
Chest, mouth, perianal, skin
- Bacterial septicaemia
- Herpes Zoster
- CMV
- Measles
- Candidiasis
- Pneumocystis Pneumonia
What are the following?
Petechiae - Small (1–2 mm) haemorrhages into mucosal or serosal surfaces
What are causes of the following?
- Thrombocytopenia of any cause - autoimmune, heparin-induced, hypersplenism
- Bone marrow failure - malignancy
- Defective platelet function
- DIC
- Infection
- Bone marrow defects
- Factor deficiencies
What is the following?
Purpura - >3 mm haemorrhages, or when ecchymoses and petechiae form in groups
What are causes of the following?
Diseases associated with:
- Trauma
- Vasculitis – particularly palpable purpura
- Amyloidosis
- Over-anticoagulation
- Factor deficiencies
What is the mechanism of colour change in bruising?
Erythrocyte -> Bilirubin (blue/green) -> Haemosiderin (yellow)
Once under the skin, erythrocytes are phagocytosed and degraded by macrophages, with haemoglobin converted to bilirubin (blue–green discolouration).
Bilirubin is eventually broken down into haemosiderin (which is golden brown) at the end of the process before skin returns to its normal hue.
What CNS involvement can occur in ALL?
- Cranial nerve palsies
- Meningism
What are poor prognostic factors for ALL?
- Age > 60yrs - “dreadful”
- White cell count > 300 x 109/L
- Immunophenotype (more primitive forms)
- Cytogenetics/molecular genetics - Philedelphia chromosome t(9;22); t(4;11)
- Slow/poor response to treatment
- Presentation with CNS signs
How would you investigate suspected ALL?
- Bedside - examination
- Bloods - FBC, U+E’s, LFTS, LDH, Urate, Coagulation screen, Blood film
- O
- X - CXR, CT Scan
- ECG - no
- Specific - Bone marrow, Consider LP
What might you see on FBC in someone with ALL?
- Normochromic, normocytic anaemia
- WBC raised usually (sometimes normal or low)
- Platelets low
What might you see on Blood film in someone with ALL?
Blast cells almost invariably seen
What proportion of bone marrow needs to be blast cells for the diagnosis of ALL to be made?
>20%
How quickly does ALL present?
2-3 weeks of bone marrow failure plus bone/joint pain
Why does someone with ALL get bone pain?
Bone fills up with blast cells
What is the prognosis for ALL?
- Cure rate children - 70-90%
- Cure rate adults - 40%
Why would you do a CXR in ALL?
Look for mediastinal widening which is characteristic of T-cell lymphoblastic leukaemia
Why would you consider doing an LP in someone with ALL?
Look for signs of CNS involvement
Why would you do a bone marrow biopsy in suspected ALL?
Look for:
- Increased cellularity, reduced erythropoiesis, reduced megakaryocytes.
- Replacement by blast cells >20%
-
Lineage confirmation by immunophenotyping
- B lineage ALL – CD10 and CD19
- T lineage ALL– CD3
- Cytogenetic FISH analysis in real-time PCR
How would you manage someone with ALL?
- Supportive Therapy
- Induction chemotherapy + CNS directed treatment
- Consolidation therapy
- Maintenance treatment for 18 months
- Stem cell transplantation (if high risk)
What chemotherapeutic medications are used for induction chemotherapy?
Over 4 weeks:
- Vincristine
- Dexamethasone
- L-asparaginase
- Daunorrubicin - high risk patients
What CNS prophylaxis would you use?
Intrathecal methotrexate +/- CNS irradiation (if known CNS involvement)
What is involved in consolidation therapy?
High-medium dose therapy in blocks over several weeks
Where is relapse of ALL most commonly found?
- Blood
- CNS
- Testis
What complications can arise from ALL?
- Neutropenic sepsis
- Hyperuricaemia - from massive cell death
- Poor growth
- CNS tumour
What might you find on investigation of serum urate and LDH in ALL?
Both increased
What might you find on CSF in someone with ALL?
- Pleocytosis (with blast cells)
- Increased protein
- Decreased glucose
What genetic disorder is associated with development of ALL, and how much does this disorder increase the risk of developing ALL?
Down’s syndrome - 4-fold increase
What age range is the peak incidence of ALL?
2-6 years. Second peak after 50 years
What supportive therapy would you use in ALL?
- Blood/Platelet transfusion
- IV fluids
- Allopurinol
- Hickman/Subcut line - IV access
Why would you give allopurinol to someone as supportive therapy for ALL?
To try to prevent tumour lysis syndrome
What are characteristics of blast cells?
An immature precursor of myeloid cells or lymphoid cells:
- Bigger than normal counterpart
- Immature nucleus (nucleolus, open chromatin)
- Cytoplasmic appearances often atypical
- Rarely ever seen in serum of normal individuals
If present, are highly suggestive of an acute leukaemia or a chronic disorder that is beginning to transform into an acute disease
