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Immunology and Haematology > Lymphoproliferative Disorders > Flashcards

Lymphoproliferative Disorders Flashcards

1
Q

How is the diagnosis of leukaemia or lymphoma made?

A

Defined by malignant cell characteristics:

  • Diagnosis made by biopsy (of lymph node or bone marrow etc)
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2
Q

How is staging done?

A
  • Clinical examination
  • CT scan
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3
Q

What does staging describe?

A
  • Location and extent of disease
  • Info about prognosis
  • Influences treatment
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4
Q

How is lymphoma classified?

A

Hodgkin lymphoma is specific disease, non-Hodgkin lymphoma is everything else (more than 70 conditions)

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5
Q

What are the main lymphoproliferative disorders?

A
  • Acute lymphoblastic leukaemia (ALL)
  • Chronic lymphoblastic leukaemia (CLL)
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma (NHL)
    • High grade (diffuse large B-cell lymphoma)
    • Low grade (follicular, marginal zone)
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6
Q

What does ALL stand for?

A
  • Acute lymphoblastic leukaemia (ALL)
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7
Q

What does CLL stand for?

A
  • Chronic lymphoblastic leukaemia (CLL)
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8
Q

What does HL stand for?

A

Hodgkin lymphoma

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9
Q

What does NHL stand for?

A
  • Non-Hodgkin lymphoma (NHL)
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10
Q

What is the most common lymphoproliferative disorder?

A

Most common is high grade NHL

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11
Q

ALL is a disorder of what cells?

A

Cancerous disorder of lymphoid progenitor cells

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12
Q

Describe the pathophysiology of ALL?

A
  • Normally immature cells that rapidly proliferate and differentiate into lymphocytes
  • In leukaemia, no differentiation and instead rapid and uncontrolled growth and accumulation
  • Usually in bone marrow but they can go anywhere
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13
Q

Describe the epidemiology of ALL?

(incidence, age)

A
  • Incidence 1-2/100,000
  • 75% cases children <6 years
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14
Q

Describe the presentation of ALL?

A
  • 75-90% cases are B-cell linage
  • 2-3 week history of bone marrow failure or bone/joint pain
  • Weight loss
  • Anaemic symptoms
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15
Q

Describe the investigations for ALL?

A
  • Blood count
    • Low haemoglobin
    • High WCC
    • Low platelet
  • Bone marrow aspirate
    • Full of B lymphoblasts
  • Blood film
    • Large cells
  • Immunophenotyping
    • Used to tell what markers cells carry
    • They express CD19 – all B cells have this
    • And express CD34, TDT – markers of very early, immature cells
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16
Q

What is seen in the FBC for ALL?

A
  • Low haemoglobin
  • High WCC
  • Low platelet
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17
Q

What is seen in the bone marrow aspirate for ALL?

A
  • Full of B lymphoblasts
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18
Q

What is immunophenotyping used for?

A
  • Used to tell what markers cells carry
  • They express CD19 – all B cells have this
  • And express CD34, TDT – markers of very early, immature cells
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19
Q

Describe the treatment of ALL?

A
  • Standard treatment - chemotherapy
    • Induction chemotherapy to obtain remission
    • Consolidation therapy
    • CNS directed treatment
    • Maintenance treatment for 18 months
  • Stem cell transplantation (if high risk)
  • Newer therapies
    • Bi-specific T-cell engagers
      • Drug – Blinatumumab
    • CAR-T cell therapy
      • Modify patients own T cells to express receptor for CD19 marker
      • Side effects – cytokine release syndrome (fever, hypotension, dyspnoea), neurotoxicity (confusion, seizure, headache, focal neurology, coma)
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20
Q

What does CAR-T cell therapy do?

A
  • Modify patients own T cells to express receptor for CD19 marker
21
Q

What are possible side effects of CAR-T cell therapy?

A
  • Side effects – cytokine release syndrome (fever, hypotension, dyspnoea), neurotoxicity (confusion, seizure, headache, focal neurology, coma)
22
Q

Describe the prognosis of ALL?

A
  • Decreases with
    • Increasing age
    • Increased white cell count
    • Cytogenetics/molecular genetics
      • T(9;22), T(4;11)
    • Slow/poor response to treatment
  • Adults
    • Complete remission 90%
    • Leukaemia free at 5 years 30%
  • Children
    • 5 year survival 90%
23
Q

Describe the epidemiology of CLL?

(gender)

A
  • Commonest leukaemia worldwide
  • M:F 2:1
24
Q

What is the commonest leukaemia?

A

CLL

25
Q

What are risk factors for CLL?

A
  • Family history
    • Occasionally familial
26
Q

Describe the presentation for CLL?

A
  • Unlike ALL, the abnormal cells are mature and usually resemble normal lymphocytes
    • Grow slowly
    • Carry many of normal B cell markers
  • Is a low grade disorder
27
Q

Describe the presentation of CLL?

A
    • Most people
  • Bone marrow failure
    • Anaemia, thrombocytopenia
  • Lymphadenopathy
  • Splenomegaly
  • Fever and sweats
  • Immune paresis (loss of normal immunoglobulin production)
  • Haemolytic anaemia
  • Less common findings
    • Hepatomegaly
    • Infections
    • Weight loss
28
Q

How is the diagnosis of CLL made?

A
  • Requires lymphocyte count of >5 (normal is <4)
29
Q

What system is used to stage CLL?

A
  • Binet system
30
Q

What are indications for treatment of CLL?

A
  • Progressive bone marrow failure
  • Massive lymphadenopathy
  • Progressive splenomegaly
  • Systemic symptoms
  • Autoimmune cytopenias
31
Q

Describe the Binet staging system?

A
32
Q

Describe the treatment for CLL?

A
  • Often ‘watch and wait’
  • Cytotoxic chemotherapy
    • Drugs – fludarabine, bendmustine
  • Monoclonal antibodies
    • Drugs – Rituximab, obinatuzumab
  • Novel agents
    • Bruton tyrosine kinase inhibitor
    • PI3K inhibitor
    • BCL-2 inhibitor
33
Q

What are examples of cytotoxic chemotherapies?

A

Drugs – fludarabine, bendmustine

34
Q

What are examples of monoclonal antibodies?

A
  • Drugs – Rituximab, obinatuzumab
35
Q

What are poor indicators for prognosis of CLL?

A
  • Advanced disease
  • Atypical lymphocyte morphology
  • Bad genetics
    • Loss or mutated p53 – chemotherapy resistant
36
Q

Describe the presentation of lymphoma?

A
  • Lymphadenopathy/hepatosplenomegaly
  • Extranodal disease
  • “B symptoms”
  • Bone marrow involvement
37
Q

How is lymphoma staged?

A
  • Lymph node biopsy/CT scan/bone marrow aspirate and trephine
  • Stages
    • I – one nodal site
    • II – 2 nodal sites, either above or below diaphragm but not both
    • III – sites above and below diaphragm
    • IV – extra-nodal involvement such as liver
    • Also use of A and B
      • A – absence of B symptoms
      • B – present of B symptoms – fever, night sweats, weight loss
38
Q

Describe the stages of lymphoma?

A
39
Q

How is NHL classified?

A
  • Linage (B-cell or T-cell)
    • Majority are B cell (90%)
  • High grade/low grade
    • Low grade – asymptomatic, responds to chemotherapy by incurable
    • High grade – aggressive and fast growing, requires combination chemotherapy, can be cured
40
Q

Is NHL usually B cells or T cells?

A
  • Majority are B cell (90%)
41
Q

What is low and high grade NHL?

A
  • Low grade – asymptomatic, responds to chemotherapy by incurable
  • High grade – aggressive and fast growing, requires combination chemotherapy, can be cured
42
Q

What is the most common low and high grade NHL?

A
  • Diffuse large B-cell lymphoma
    • Commonest lymphoma
    • High grade
  • Follicular lymphoma
    • 2nd commonest
    • Low grade
43
Q

What is the commonest lymphoma?

A
  • Diffuse large B-cell lymphoma
    • Commonest lymphoma
    • High grade
44
Q

Describe the treatment for NHL?

A
  • Combination chemotherapy
    • Typically anti-CD20 monoclonal antibody and chemotherapy
45
Q

Describe the epidemiology of HL?

(age, sex)

A
  • 30% all lymphomas
  • Bimodal age curve
    • Peak in teenage and young adult, then another peak in late life
  • M:F 2:1
46
Q

What are risk factors for HL?

A
  • Associated with EBV
  • Familial
47
Q

What virus is HL associated with?

A

EBV

48
Q

Describe the treatment for HL?

A
  • Combination chemotherapy (ABVD)
  • With or without radiotherapy
  • Monoclonal antibodies (anti-CD30)
  • Immunotherapy (checkpoint inhibitors)
  • PET scanning to assess response to treatment

Immunology and Haematology (23 decks)

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