Leukaemia Flashcards
What is a leukaemia and what are the types
haemopoietic cells lose their ability to differentiate/mature into the end cells, remaining as precursor cells (blasts)
> 20% blast cells
Acute lymphoblastic = build up of lymphoid blast cells
Acute myeloid = build up of myeloid blast cells
Chronic leukaemia = the haemopoietic cells proliferate and differentiate but are non-functioning
What is the most common leukaemia in children
Acute lymphoblastic leukaemia (ALL) (80%)
85% are B-lineage, 5% T cell lineage
What are the causes of ALL
proliferation of lymphoblasts (primitive lymphoid cells) → replacement of normal marrow → bone marrow failure and infiltration into other tissues
If build-up of B lymphoblasts → B-ALL (C10, C19, C20 surface markers)
If build-up of T lymphoblasts → T-ALL (CD2-CD8)
What are the causes of AML
proliferation of myeloblasts (primitive WBCs) → Replacement of normal bone marrow elements → bone marrow failure
Monoblast AML
Megakaryoblast AML
Erythroblast AML
What are the risk factors for ALL
Radiation
Viruses
Down’s syndrome
NF1
Fanconi’s anaemia
Achondroplasia
Xeroderma pigmentosum
Siblings with ALL
What are the symptoms of leukaemia
Bone marrow failure
- Anaemia: pallor, lethargy, SOB
- Thrombocytopenia: bleeding gums, bruising, menorrhagia
- Neutropenia: opportunistic, recurrent infection
Local infiltration
- Lymphadenopathy
- Splenomegaly
- Testes, CNS (Sanctuary sites where chemotherapy cannot reach easily)
- Bone pain
What are the signs of ALL on examination
Testicular swelling
Thymic swelling
Hepatosplenomegaly
Lymphadenopathy
Tender bones
Mediastinal compression
Cranial nerve palsies
Retinal haemorrhage or papilloedema, leukaemic infiltration of the anterior chamber of the eye
What are the signs of AML on examination
Gum swelling/hypertrophy
CNS involvement (headaches, nausea, diplopia)
Skin rashes
Rare: deposits of leukaemic blasts in the eye, tongue and bone (fractures)
What investigations should be done for leukaemia
FBC: anaemia, neutropenia, thrombocytopenia
Clotting studies
Blood film
Cytochemistry (B or T lineage)
Immunohistochemistry
CXR: enlarge thymus, mediastinal lymphadenopathy, lytic bone lesions
Bone marrow biopsy: >20% blasts
Lumbar puncture
Bone radiograph: mottled appearance, “punched out” lesions
What is tumour lysis syndrome
↑ potassium, LDH, phosphate, uric acid
What are the diagnostic features specific to ALL
Blood film: positive TdT staining
What are the diagnostic features specific to AML
Blood film: Auer rods (myeloperoxidase crystalloid)
Immunohistochemistry: Myeloblast granules positive for Sudan Black staining
What is the management for leukaemia
- Reduce tumour lysis syndrome (WCC raised) → allopurinol, hyperhydration
- Cross match for blood tranfusion
- Transfer to specialist centre
- Platelet transfusion
- Bone marrow aspirate
- Chemotherapy (remission (pred) → maintenance (6-Mercaptopurine)
+ supportive care
- Blood products
- Antibiotics for any fever
- Prophylactic Abx to prevent PCP
- Anti-emetics
- Intrathecal methotrexate for CNS involvement
What is the prognosis for leukaemia
Children: 5-year disease-free survival of 80%
Adults: 5-year disease-free survival of 30-40%
Poor prognostic markers:
Age <2 or >10
Non-Caucasian
T/B-cell surface markers
Male sex
What are the causes of CLL
Accumulation of incompetent lymphocytes
Autoimmune disease:
- Haemolytic anaemia (10%)
- Thrombocytopenia
- Combination (Evan’s syndrome)
What are the symptoms of chronic leukaemia
May be asymptomatic
Systemic: weight loss, sweating
Bone marrow failure
- Anaemia → pallor, lethargy, SOB
- Thrombocytopenia → bleeding gums, bruising, menorrhagia
Abdominal discomfort, early satiety
Gout or hyperviscosity symptoms (headaches, visual disturbance, pruritus, worse after bath)
Blast crisis with symptoms of AML or ALL
What are the signs of chronic leukaemia on examination
Splenomegaly (90%)
Bone marrow failure → cardiac flow murmur
Lymphadenopathy
What would investigations show for chronic lymphocytic leukaemia
FBC: Anaemia | thrombocytopenia | raised lymphocytes | reduced serum immunoglobulins
Blood film:
- Smudge/smear cells
- Small lymphocytes
Bone Marrow aspirate/biopsy: lymphocytic replacement (25-95%) of normal marrow
What is the management for chronic lymphocytic leukaemia
Stage via Rai and Binet systems
If asymptomatic → Watchful waiting
± chemotherapy, prednisolone, Abx prophylaxis, blood products, splenectomy, HSCT
What are the complications of chronic lymphocytic leukaemia
15% transform into localised high-grade non-Hodgkin’s lymphoma (Richter’s transformation) or Prolymphocytic leukaemia
Chemotherapy complications (tumour lysis syndrome)
What is the prognosis for chronic lymphocytic leukaemia
Best for early disease
11q and 17p deletions associated with poor survival
Gram –ve and encapsulated organisms are most frequent cause of morbidity and mortality in CLL
What is the aetiology of chronic myeloid leukaemia
Chromosomal translation t(9,22): Philadelphia Chromosome (95%) - fusion of genes BCR and ABL → Increase tyrosine kinase activity → cell replication
What are the phases of CML
- Relative stable chronic phase of variable duration (4-6 years)
- Accelerated phase (3-9 months)
- Acute leukaemia phase - blast formation
What are the signs of CML on exam
Splenomegaly (90%)
Bone marrow failure → cardiac flow murmur
What investigations should be done for CML
FBC - Raised WCC, basophils, eosinophils, neutrophils, platelets + Reduced Hb
Raised uric acid
Reduced neutrophil alkaline phosphatase
Raised vit B12 and trascobalamin
Blood Film
- Immature granulocytes
- Left shift
Bone Marrow trephine biopsy or aspirate:
- Hypercellular
- Raised myeloid-erythroid ratio
Cytogenetics: Philadelphia chromosome (t9:22)
What is the management for CML
Specific treatment: Imatinib and Dasatinib (tyrosine kinase inhibitor) act as inhibitors of BCR-ABL
Chronic phase: Hydroxyurea or IFN-𝝰, with Allupurinol to prevent hyperuricaemia and gout
Stem cell transplant: allogeneic, autogenous
Acute phase: Treat as AML/ALL
What are the complications and prognosis of CML
Transformation into acute leukaemia (80% AML, 20% ALL)
Depends on age, spleen size, % blasts in blood, platelet count
Mean survival 5 years
20% survive >10yr
