Haematology 2 Flashcards
What causes leukaemias?
Unknown but associated with:
Radiation
Chemical agents (benzene)
Oncogenic viruses
Smoking
Genetic predisposition
How are leukaemias classified?
Based on primary haematopoietic cell line affected (myeloid or lymphoid)
Based on clinical behaviour (Acute or chronic leukaemia)
Simplest 4 categoried:
Acute Myelogenous leukaemia (AML)
Acute Lymphocytic Leukaemia (ALL)
Chronic Myelogenous leukaemia (CML)
Chronic Lymphocytic Leukaemia (CLL)
How can leukaemia be diagnosed?
FBC
Bone marrow biopsy
Additional methods (Flow cytochemical staining)
Cytometric immunophenotyping
Genetic analysis
What would a FBC show in a case of leukaemia?
Peripheral granulocyte cound increase in chronic leukaemia
Increase or decrease or normal in acute leukaemia
What are the types of myeloid neoplasms?
Acute myeloid leukaemia
Myeloproliferative disorders: Chronic myelogenous leukaemia (CML) Polycythemia vera Essential thrombocythemia Systemic mastocytosis Chronic eosinophilic leukaemia Stem cell leukaemia
Myelodysplastic syndromes
What is acute myelogenous leukaemia?
Clonic proliferation of immature WBC (blasts) in the bone marrow and subsequently in the blood.
What percentage of leukaemias are AML?
1/3 of all leukaemia
Who gets AML most often?
Adults increases in incidence with age (mean age 65yo)
Male to Female ratio 5:3
What causes AML?
De novo
Environmental causes: Tobacco, benzene containing compound, chemotherapy
Consequence of myelodysplastic syndrome (30% of MDS-es progress to AML)
Genetic factors (Translocations and rearrangement of gases. Down syndrome, klinefeller syndrome, fanconi anaemia, recklinghausen
What are the clinical signs of AML?
Anaemia related: Shortness of breath, weakness, dyspnea on exertion
Physical findings: Pallor, bleeding/bruising, hepatomegaly, and/or splenomegaly.
Otherwise unexplained headache or focal neurological complaints.
Pancytopaenia save for WBC
Accumulation of leukemic forms in the peripheral blood, bone marrow and/or other tissues
How is AML diagnosed?
> 20% BM cellular component = myeloid blasts/promyelocytes
Myeloblasts: Delicate nuclear chromatin, 3 to 5 nucleoli, fine azurophilic cytoplasmic granules.
Auer rods
What are auer rods?
Red staining rod-like structures. Numerous in acute promyelocytic leukaemia. Specific for neoplastic myeloblasts
How is AML treated?
Phases of therapy include:
Induction therapy: Intensive combination chemotherapy to achieve a CR through reducing the number of leukaemia cells and restoring normal bone marrow function.
Post-remission therapy: Chemotherapy, targeted therapies, and autologous or allogenic haematopoietic cell transplantation
What is CML?
Myeloproliferative neoplasm with dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation
What happens in CML?
BCR (chromosome 22) fuses with ABL1 (Chromosome 9) creating a philadelphia chromosome and a protein results from this leading to elevated and constitutive kinase activity leading to CML
How can CML be diagnosed?
FISH allows visualization of the BCR-ABL gene
How common is CML?
Accounts for approximately 15 - 20% of adult leukaemias in adults.
Annual incidence of 1 to 2 cases per 100k
Slight male predominance
Median age is 50 years
What are the risk factors for CML?
No known familial dysposition (except familial CML on JAK2 and Ph chromosome)
Only risk factor known is ionizing radiation.
How does CML present?
Triphasic or biphasic clinical course:
Chronic phase: Present at the time of diagnosis.
Accelerated phase: Progressively impaired neutrophil differentiation and difficulty in controlling leukocyte counts with treatment.
Blast crisis: Resembling acute leukaemia
What are the clinical findings associated with CML?
Asymptomatic in 20 - 50% of cases
In symptomatic patients: Fatigue (34%), malaise, weight loss, excessive sweating, abdominal fullness, and bleeding episodes
How is CML treated?
Imatinib blockes BCR-ABL
Why is imatinib relevant to dentists?
imatinib may lead to mucosal pigmentation of a grey blue colour,
What Condition has overlapping clinical symptoms with acute lymphoblastic leukaemia?
Acute lymphoblastic lymphoma
What happens in ALL /LBL?
Clonal proliferation of lymphoid cells that have undergone maturational arrest in early differentiation.
Both pre-B and pre-T cell tumours take on the clinical appearance of ALL during their course.
What cells are most commonly involved in B/T-ALL/LBL?
Precursor to B lymphocytes (85%)
T lymphocytes in 10 - 15%
Uncommon variants in <1% (early T and NK cells)
Who most commonly gets B/T-ALL/LBL?
Most common in children
2500 to 3500 new cases of ALL/LBL are diagnosed in children each year.
3.4 cases per 100000
Peak incidence at 2 - 5 years
More common in boys
Incidence is increasing
What are the risk factors for ALL/LBL?
Unknown cause
Genetic and environmental influence
Advanced paternal age and maternal foetal loss
Increased birth weight
Not a familial disease
How is ALL diagnosed?
Characteristic morphology
Diagnostic immunohistophenotype of cells from:
Peripheral blood
Bone marrow
Lymph node
Other involved tissue
Markers:
B-lymphoblasts: CD19, cytoplasmic CD79a, and cytoplasmic CD22
T-lymphoblasts: CD3
What is the prognosis of B/T-ALL/LBL?
Poor prognosis for ages =<1 and >=10 yo, leukocyte count >=50000/microL, race, and male
What is the treatment for ALL/LBL?
Administration of a multidrug regimen: Induction, consolidation, and maintenance. Takes 2 - 3 years to complete.
Transfusion support
Treatment of proven and suspected infections
Correction of metabolic imbalances
Leukopheresis (rarely)
How is the induction treatment carried out for ALL/LBL?
90% of children achieve complete remission at the end of induction.
initial treatment in BCR-ABL1 positive ALL is imatinib
Weekly vincristine (3 - 4 weeks), Daily corticosteroids and asparaginas in BCR-ABL negative
What is different for children with down-syndrome in terms of ALL?
Susceptible to adverse events and treatment-related mortality
• Severe mucositis in response to MTX
• Increased risk of infection
• Reduced intensity chemo
What are the goals for post remission therapy?
Started soon after CR
Goal:
Prevent leukaemic regrowth
Reduce residual tumour burden
Prevent the emergence of drug-resistance in the remaining leukaemic cells
How long does consolidation last? What drugs does it include?
4 - 8 months
Includes:
Cytarabine
Methotrexate
Anthracyclines
Alkylating agents (Cyclophosphamide, ifosfamide)
Epipodophyllotoxins
