University of Sydney Medical Program Year 1
LYMPHOMA... WHAT IS IT?
Haemopoiesis
AML
ALL
Lymphoma/ CLL
B lymphoid
erythroid myeloid megakaryocytic
T lymphoid
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
Lymph node structure
• follicle centres contain predominantly B cells • cortical regions contain predominantly T cells
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
B cell malignancies
Bone marrow
Lymph node, lymph, blood, bone marrow
Lymph node, lymph, blood, bone marrow
Bone marrow
Progressive B lymphocyte maturation
Lymphoid stem cell
Maturing B cell many stages
Mature B cell
Plasma cell
Pre-B acute lymphoblastic leukaemia
B cell lymphoma
Chronic lymphocytic leukaemia
Multiple myeloma
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
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)
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
Making the diagnosis
nodular (follicular) diffuse
Indolent
Aggressive
small cell
large cell
Gene translocations in lymphoma
• transcription of new or existing gene
producing mRNA
• translation of mRNA producing protein
t(14:18) IgH/bcl-2 t(11:14) IgH/bcl-1 t(8:14) IgH/c-myc
apoptosis through bcl-2 cell cycle via cyclin D cell cycle via c-myc
indolent lymphoma mantle cell lymphoma Burkitts lymphoma
Gene translocation t(14;18) leads to overexpression of bcl-2 and inhibition of apoptosis in B cells
Chr 18 Chr 14
VH (100–200) D (>20) J (6)
bcl-2
IgH Locus
Cm
Recombinase t(14;18) bcl-2 Cm
Adapted from Liu Y et al. Proc Natl Acad Sci 1994
Permission requested from Proceedings of the National Academy of Science
Light chain restriction to determine monoclonality
K K L K L L K L K L L L K L K L L K K
L
L K K
K
L
L L
L L
L L L
L L L L L
L L L K
L
L
L K
L
Lymphoma staging
Stage with blood count, biochemistry, CT chest/abdomen/pelvis and bone marrow biopsy
Treatment strategies
Grow slowly
(indolent)
Treat slowly
1. Watch and wait
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 often with radiation therapy to sites of bulky disease
(aggressive, highly aggressive)
2. Consider autologous or allogeneic stem
cell transplantation for initial treatment failures
Common anti-lymphoma drugs
• chlorambucil • CHOP
– – – – cyclophosphamide doxorubicin vincristine prednisone)
• fludarabine • anti-CD20 antibody
Outcomes
Indolent
– cure none – median survival 8 years – 25% alive at 10 years
Aggressive/Highly aggressive
– cure 30-40% – 50% dead in 2 years
100
% s u r v i v a l
80 60 40 20 0 0 2 4 6 8
Low-grade Intermediate-grade High-grade
10
Years from diagnosis