Haemopoiesis

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University of Sydney Medical Program Year 1
LYMPHOMA... WHAT IS IT?
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Haemopoiesis
ALL
AML
Lymphoma/ CLL
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Types of lymphocytes (defined by surface
antigens, in vitro function, types of illness
when lacking)

• B cells humoral immunity
• antibody production
• T cells cellular immunity
• cytotoxicity against virus, fungus
• B cell help

Most lymphomas are of B cell type
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Lymph node structure

• follicle centres contain predominantly B cells
• cortical regions contain predominantly T cells

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Normal B cell behaviour
1. Pre-B cell differentiates from lymphoid stem
cell in bone marrow or thymus
2. B cells mature and circulate through lymph
node, lymphatics, blood and bone marrow
3. B cell meets antigen in lymph node and
differentiates into antibody secreting plasma
cell
B
T
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B cell malignancies
Lymph node, lymph, blood, bone marrow
Lymph node, lymph, blood, bone marrow
Bone marrow
Bone marrow
Progressive B lymphocyte maturation
Lymphoid stem cell
Mature B cell
Plasma cell
Maturing B cell many stages
Pre-B acute lympho- blastic leukaemia
B cell lymphoma
Chronic lympho- cytic leukaemia
Multiple myeloma
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Types of lymphoma

• Indolent lymphoma
• nodular or follicular lymph node pattern
• slowly growing
• respond to treatment but incurable
• treatment can be observe only or start with mild
  and simple therapy

• Aggressive/highly aggressive lymphoma
• diffuse lymph node pattern
• grow rapidly
• some cured (30-40)
• those not cured die within 1-2 years
• require aggressive initial chemotherapy to
  attempt cure

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How does lymphoma present to the doctor?

• Patient notices lumps in neck, under arms, in
  groin (lymphadenopathy)
• Lymphadenopathy noted during examination for
  other reason eg. check up
• Abnormal blood findings unusual (cf. leukaemia)

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Making the diagnosis

• Surgical node biopsy is essential at initial
  diagnosis
• Fine needle aspiration biopsy can be useful to
  confirm disease where biopsy is difficult eg.
  lung, liver or to document relapse but only
  after diagnosis has been established by node
  biopsy

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Making the diagnosis
nodular (follicular)
diffuse
Indolent
Aggressive
large cell
small cell
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Gene translocations in lymphoma
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Gene translocation t(1418) leads to
overexpression of bcl-2 and inhibition of
apoptosis in B cells
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Light chain restriction to determine monoclonality
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
L
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Lymphoma staging
Stage with blood count, biochemistry, CT
chest/abdomen/pelvis and bone marrow biopsy
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Treatment strategies
Grow slowly Treat slowly 1. Watch and
wait (indolent) 2. Local radiation for local
disease 3. Start with simple chemotherapy and
move to more complex chemotherapy Grow
fast Treat fast 1. Aggressive multiagent
chemotherapy (aggressive, highly aggressive)
often with radiation therapy to sites of
bulky disease 2. Consider autologous
or allogeneic stem cell transplantation
for initial treatment failures
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Common anti-lymphoma drugs

• chlorambucil
• CHOP
• cyclophosphamide
• doxorubicin
• vincristine
• prednisone)
• fludarabine
• anti-CD20 antibody

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Outcomes

• Indolent
• cure none
• median survival 8 years
• 25 alive at 10 years

• Aggressive/Highly aggressive
• cure 30-40
• 50 dead in 2 years

s u r v i v a l
Years from diagnosis