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year 4 CDM 2 > Case 15: Leukaemia > Flashcards

Case 15: Leukaemia Flashcards

1
Q

ALL investigations

A
  • FBC: thrombocytopaenia, anaemia, low WBC (but can be high)
  • Blood film: abnormal cells and inclusions
  • U&E, LFT, CRP, ESR, Coag screen, Lactate
  • Bone marrow aspiration: only need Biopsy if insufficient cells. Diagnose when lymphoblasts occupy >20% of bone marrow
  • Lymph node biopsy: if abnormal lymph nodes
  • CT and PET: stage disease
  • Genetic tests: to guide treatment
  • Lumbar puncture: in all patients with ALL to assess for CNS involvement
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2
Q

Special tests for ALL

A
  • Organ specific investigations (CXR, CT, LP)
  • Bone marrow biopsy: Blast cells >20%
  • Biopsy of infiltrated organs
  • Immunophenotyping to identify subtype (B or T cell) and confirms diagnosis
  • Cytogenetics for prognostic info and sub-categorise ALL
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3
Q

Initial management of ALL

A
  • Treating any infection, metabolic complication and if indicated giving a transfusion to stabilise the patient.
  • Following diagnosis, initial management or pre-phase therapy is started for 5-7 days;
    • Corticosteroids with or without another drug
    • Hydration
    • Allopurinol
  • CNS prophylaxis is given intrathecally
  • Baseline evaluation: LFT, U&E and an echocardiogram
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4
Q

General principles of chemo regime for ALL

A
  • Induction: reduce leukaemia to <5% of blasts and restore normal Haematopoiesis. Assessed after 6-16 weeks
  • Consolidation: prevent the growth ofleukaemia from any residual cells (known as a minimal residual disease (MRD) and drug resistance by using numerous drugs
  • Maintenance: use less intense agents and aims to prevent relapse. Normally use daily 6-mercaptopurine and weekly methotrexate.
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5
Q

ALL: goals of consolidation

A
  • Aim for complete remission
  • In high risk cases where complete remission isn’t achieved offer Haematopoietic cell transplantation
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6
Q

Management principles ALL

A
  • RBC transfusions
  • Platelet transfusions
  • Antibiotics for infection
  • Chemotherapy
  • Stem cell transplant if high risk
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7
Q

ALL: disease related complications

A
  • Pancocytopaenia: bone marrow suppression either from the disease or medication. Causes Thrombocytopaenia, anaemia and/or neutropoenia
  • Leukostasis: when lots of lymphoblasts are circulating peripherally. Leading to impaired circulation and perfusion of organs. Most commonly the lungs, brain and eyes
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8
Q

Tumour lysis syndrome

A
  • Lymphoblasts lyse and release their contents
  • Metabolic abnormalities: Hyperkalaemia, Hyperphosphatemia, Hyperuricaemia, Hypocalcaemia
  • Following induction therapy
  • Treatment: IV fluids, allopurinol, monitoring
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9
Q

Acute myeloid leukaemia

A
  • Most common form of acute leukaemia in adults- mean age is 65
  • Most patients achieve remission but relapse is common
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10
Q

AML risk factors

A
  • Pre-existing haematological disorders: myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH)
  • Congenital disorders:Down’s syndrome, Bloom syndrome
  • Environmental exposure: priorchemotherapy, radiation, tobacco smoke, benzene
  • Majority of cases are do novo malignancy in previously healthy individuals
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11
Q

AML clinical features

A
  • Pancytopaenia: anaemia, bleeding, infections with fever
  • Low WCC: Fever, mouth ulcers
  • Low platelets: Bleeding, bruising (Ecchymosis, Petechiae)
  • Weight loss
  • Anaemia: fatigue, dizziness, breathlessness
  • Bone pain
  • Leukaemia cutis: nodular violet lesions on the shins
  • Infiltration of leukaemic cells: Splenomegaly, Lymphadenopathy and swollen gums
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12
Q

AML investigations

A
  • FBC: Normocytic, normochromic anaemic. Thrombocytopaenia, low leukocyte count
  • Peripheral blood smear: raised myeloblasts and Auer rods
  • U&E, coagulation profile, Lactate
  • Bone marrow aspiration and biopsy: Confirmatory test
  • T (8;21): causes poor prognosis in AML
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13
Q

Bone marrow biopsy and aspiration: AML

A
  • > 20% myeloblasts in bone marrow confirm AML
  • Will show hypercellular marrow and sometimes Auer rods
  • Immunophenotypingby flow cytometry: antigens expressed CD34, HLA-DR, CD117, CD13, and CD33
  • Cytogenetics: study chromosome location and function
  • Fluorescence in situ hybridisation (FISH): detecting specific DNA, Abnormalities can define AML irrespective of blast count
  • Molecular analyses: abnormalities in specific genes
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14
Q

Acute Promyelocytic Leukaemia (APL)

A
  • A subtype of AML that causes a medical emergency
  • APML; M3 subtype
  • The translocation t(15;17) – with a reciprocal translocation involving theRARAgene. Detected on genetic testing allowing for diagnosis
  • Causes Life threatening coagulopathy
  • Good prognosis with chemo
  • Get large number of Auer rods
  • Treatment: all-trans retinoic acid (ATRA)and arsenic
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15
Q

Chemotherapy principles

A
  • Induction Chemotherapy: intensive combination chemo to achieve complete remission.
  • Consolidation Chemotherapy: An intensive treatment that follows complete remission, to destroy remaining tumour cells
  • Maintenance Chemotherapy: Non-myelosuppressive treatment. To maintain remission.
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16
Q

Chemotherapy timing

A
  • ALL: up to 3 years
  • AML: 6-8 months
  • What chemotherapy agent is recommended for ALL involving the Philadelphia chromosome: Imatinib
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17
Q

Supportive treatment for AML

A
  • Preventing and treating infections:
    • Antibiotic prophylaxis (broad-spectrum IV antibiotics) for febrile neutropenia.
    • Trimethoprim-sulfamethoxazole for pneumocystis pneumonia prophylaxis in neutropenic patients.
    • Immunisations
    • Surveillance for infections.
  • Nutritional support
  • Antiemetics (ondansetron)
  • Transfusions for severe anaemia, thrombocytopaenia
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18
Q

AML: treatment after chemo

A
  • Haematopoietic cell transplantation (HCT): for patients who don’t achieve remission through chemo
  • A long dwelling catheter i.e. PICC to administer medication
  • Cryopreservation due to risk to fertility with chemo
  • Allopurinol: prevent tumour lysis
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19
Q

Complications of AML

A
  • DIC: especially in APML
  • Leukostasis: extremely elevated blast cell count, causes respiratory and/or neurological distress
  • Tumour lysis syndrome: when cancer cells break down quickly in the body, levels of uric acid, potassium, and phosphorus rise faster than the kidneys can remove them
  • Severe neutropaenia
  • Death: poor long term prognosis
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20
Q

Chronic Lymphocytic Leukaemia

A
  • Monoclonal proliferation of B-lymphocytes in the blood or bone marrow
  • Most common Leukaemia in adults in the West
  • Most common in older adults
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21
Q

Pathophysiology of CLL

A
  • Deletion of chromosomes i.e. 13q, 11q and 17p chromosomes
  • Destruction of blood cells causing: anaemia, neutropenia, thrombocytopenia, and decreased immunoglobulin production.
  • Transformation of CLL to aggressive forms: can evolve into B-cell pro-lymphocyticleukaemia and transform to a higher grade non-Hodgkin lymphoma
22
Q

CLL: Clinical features

A
  • Majority are asymptomatic at presentation
  • Lymphadenopathy
  • Hepatomegaly and/or Splenomegaly causing abdo discomfort
  • Infections i.e. Pneumonia and VZV
  • Anaemia, bleeding, bruising
  • B symptoms: night sweats, weight loss, high fever
23
Q

CLL investigations

A
  • FBC, U&E, LFT, CRP, ESR, Reticulocyte count, DAT, Immunophenotype (gold standard)
  • FBF: absolute lymphocytosis (>5,000 lymphocytosis), anaemia, raised WCC, Thrombocytopaenia
  • Peripheral blood smear: confirm lymphocytosis, Smudge cells
  • Before treatment: detect TP53 gene as associated with worse prognosis
  • Consider bone marrow biopsy
  • Consider Lymph node biopsy if enlarged
24
Q

CLL: Immunophenotyping

A
  • Confirms CLL
  • Detect antibodies specific for CD5, CD19, CD20, CD23
25
Q

Management of CLL

A
  • Not curable but treatable
  • Binet A-B: watchful waiting (3 monthly FBC, flow cytometry and examination:
  • Binet C or active/symptomatic disease: chemotherapy (usually FCR regime), stem cell transplant for refractory disease
26
Q

Chemotherapy: CLL

A
  • Initial therapy: Fludarabine, cyclophosphamide and rituximab (FCR)
  • TP53 deletion: Ibrutinib
  • Main complication of CLL is auto-immune Cytopenia which can be treated with corticosteroids
27
Q

Binet staging

A
  • Stage A: Hb at least 10 g/dL, platelets at least 100 x 109/L, and <3 lymph node areas involved.
  • Stage B: Hb and platelet levels as in stage A and >3 lymph node areas involved.
  • Stage C: Hb <10 g/dL, platelets <100 x 109/L, or both.
  • Even if lymph nodes are affected in both underarms it counts as one
28
Q

Complications of CLL

A
  • Recurrent infections
  • Autoimmune haemolytic anaemia
  • Richter transformation
  • Hyper viscosity syndrome: CNS and/or respiratory insufficiency i.e. headache, dizziness, vertigo
  • Malignancies i.e. melanoma, colorectal cancer
29
Q

Richter’s transformation

A
  • Transformation of CLL to a high grade non-Hodgkins lymphoma, often fatal
  • Occurs when Leukaemia cells enter the lymph node
  • Present: patient becomes very unwell with lymph node swelling, fever and weight loss
30
Q

Chronic Myeloid Leukaemia: mutation and age

A
  • Philadelphia chromosome: present in 95% of CML. Due to translocation between chromosome 9 and 22 t(9:22)(q34; q11). Creates a fusion gene called BCR-ABL1 which encodes p210 tyrosine kinase
  • Tend to be 60-70
31
Q

CML presentation

A
  • anaemia: lethargy
  • weight loss and sweating are common
  • splenomegalymay be marked → abdo discomfort
  • an increase in granulocytes at different stages of maturation +/- thrombocytosis
  • decreased leukocyte alkaline phosphatase
  • may undergo blast transformation (AML in 80%, ALL in 20%)
32
Q

CML investigations

A
  • FBC: anaemia, raised WCC. Thrombocytopenia in blast phase and high platelets in chronic phase
  • blood film: Increased granulocytes esp neutrophils
  • bone marrow biopsy: granulocytic hyperplasia
  • cytogenetics (FISH): detects Philadelphia chromosome
33
Q

CML management

A
  • First line: Imatinib. If good response don’t have to use long term
  • If no response to Imatinib can change to 2nd generation Tyrosine kinase inhibitor (nilotinib, dasatinib, bosutinib)
  • Chemo is given for 6-8 months
  • hydroxyurea
  • interferon-alpha
  • allogenic bone marrow transplant if refractory
  • Monitor BCR-ABL1 and FBC for response
34
Q

Imatinib

A
  • Inhibitor of the BCR-ABL tyrosine kinase defect by competing with ATP binding and preventing phosphorylation (Tyrosine kinase inhibitor). Very high response rate in chronic phase CML
  • Side effects: cramps, oedema, rash diarrhoea
35
Q

Monitoring treatment response to CML

A
  • RT PCR 3 monthly
  • FBC weekly (initially)
36
Q

CML: three phases

A
  1. Chronic phase: asymptomatic or have mild symptoms. The number of abnormal white blood cells increases gradually.
  2. Accelerated phase: the disease becomes more aggressive. Symptoms may worsen, and the number of abnormal cells increases more rapidly.
  3. Blast phase (or acute phase): The most severe phase where CML transforms into an acute leukemia, resembling acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The number of immature cells (blasts) in the blood and bone marrow increases significantly.
37
Q

Lymphadenopathy history

A
  • Tend to present with enlarged lymph nodes in cervical region and groin. Tend not to be painful
  • Symptoms: abdo pain or neurological symptoms in CNS lymphoma
  • Weight loss, night sweats
  • Risk factors: HIV/TB
  • Can be due to cat scratch
  • If lymph nodes are hard to palpate its unlikely to be lymphoma
38
Q

Lymphoma findings

A
  • Skin bruising
  • Normal FBC unless severe where there’s low platelets
  • Can have CNS involvement: do neurological exam
39
Q

Regional or generalised lymphadenopathy

A
  • Regional lymphadenopathy: local infection, less commonly cancer
  • Generalised: infection, infiltration (lymphoma, carcinoma mets, sarcoidosis)
  • Generalised: EBV, CMV, TB, HIV, syphilis, toxoplasmosis
40
Q

Lymphadenopathy: when to refer to a specialist

A
  • All patients with a lymph node >1cm for >6 weeks
  • All patients with generalised lymphadenopathy i.e. in two more non-contiguous areas
  • Supraclavicular nodes are more worrying than inguinal adenopathy
41
Q

Lymphoma investigations

A
  • Bloods: FBC, U&E, LFT, ESR (prognostic for Hodgkin’s), LDH (cancer marker for lymphoma), Immunoglobulin (elevated in cancer), Viral screen (HIV, Hep B, Hep C, EBV)
  • CXR- widened Mediastinum
  • Lymph node biopsy required for diagnosis: Core biopsy via USS or CT guidance, if not adequate use surgical excision
  • Biopsy analysed for morphology, cytogenetics (FIISH), genetic profiling
42
Q

Lymphoma staging

A
  • CT neck, chest, abdo, pelvis
  • PET required for some subtypes: FDG uptake reflects malignant cells
  • MRI brain and spine for CNS lymphoma
  • Staged using Ann Arbor score
43
Q

Ann-Arbor staging

A
  • I: single lymph node
  • II: 2 or more lymph nodes/regions on the same side of the diaphragm
  • III: nodes on both sides of the diaphragm
  • IV: spread beyond lymph nodes
  • A: absence of B symptoms
  • B: fever, night sweats, weight loss
  • Most advanced stage: IV B
44
Q

Hodgkins vs Non-Hodgkins lymphoma

A
  • NHL: >50 types. Some are low grade and don’t need treatment (watch and wait). Some high grade and need treatment
  • HL: mostly high grade and need treatment
45
Q

Tumour lysis syndrome

A
  • Risk with Lymphoma as respond well to treatment
  • Where there is massive breakdown of tumour- can cause renal failure, rise K+ and cause cardiac arrest
  • Large tumour bulk
  • Hydrate the patient
  • Give: Allopurinol and Raspuricase for prevention before
  • Close monitoring of the patient: twice daily bloods
46
Q

What does tumour lysis syndrome cause

A
  • hyperkalaemia
  • hyperphosphataemia
  • secondary hypocalcaemia
  • hyperuricaemia
  • acute renal failure
47
Q

Symptoms of tumour lysis syndrome

A
  • N/V
  • diarrhoea
  • lethargy
  • cardiac dysrhythmia
  • syncope
  • tetany
  • death
48
Q

Lymphoma complications

A
  • Tumour lysis syndrome
  • Hypercalcaemia: confusion, dehydration, abdo pain
  • Spinal cord compression: neurological symptoms (back pain, weakness, sensory), bladder-bowel disturbance. Do urgent MRI
  • Superior vena cava obstruction: commonly in large mediastinal lymphoma
49
Q

SVC obstruction presentation

A
  • SOB (most common symptom)
  • swelling of face, neck and arms
  • visual disturbance
50
Q

How does Lymphoma differ from Leukaemia

A

Leukaemia arises in bone marrow in blood. Lymphoma is present in the lymph nodes

year 4 CDM 2 (39 decks)

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