Lymphoma

1. Malignant lymphoma
Principles of management
Y.L. Kwong
Department of Medicine
University of Hong Kong

2. Blood cancer 血癌
Lymphomas 淋巴腫瘤
Leukaemias 白血病
Myeloproliferative 骨髓增生性腫瘤
neoplasm (MPN)
Myelodysplastic 骨髓發育不良症候群
syndrome

3. What is a blood cancer?
A malignancy that arises from the
haematopoietic and lymphopoietic system
Haematopoietic system
leukaemias, myeloproliferative neoplasms
myelodysplastic syndrome, plasma cell
neoplasms
Lymphopoietic system
Malignant lymphomas

4. Objectives
1. What are lymphomas ?
2. What are the clinical manifestations
of lymphomas ?
3. How are lymphomas diagnosed and
classified ?
4. What are the common lymphomas ?
5. What are the principles of treatment
of lymphomas ?
Malignant lymphomas

5. Basic concepts
1. Lymphomas are clonal malignancies
of the lymphoid system
2. The lymphoid system consists of
three distinct lineages:
B cells
T cells
Natural killer (NK) cells
Malignant lymphomas

6. Malignant lymphomas
Basic concepts
3. Lymphomas can arise from any
of the three lymphoid lineages
B cells: B cell lymphoma
T cells: T cell lymphoma
NK cells: NK cell lymphoma
4. B cell lymphomas are the most
common, followed by T cell
lymphoma and NK cell lymphoma

7. Malignant lymphomas
B cells
Rearranged
IgH gene
T cells
Rearranged
TCR gene
B cell lymphoma
Clonal rearrangement of IgH
T cell lymhoma
Clonal rearrangement of TCR
Lymphoma stem cell

8. Malignant lymphomas
Epidemiology of lymphomas
1. Causes largely unknown
2. May be related to infection with viruses
Epstein Barr virus
HTLV-1
HIV
3. Disease incidence increases with age
Extremely uncommon in children
Not common in young adults

9. Malignant lymphomas
Clinical manifestations of lymphoma
1. Enlargement of involved tissue
Nodal: lymph nodes
Extranodal: other organs
2. Systemic symptoms (B symptoms)
Unexplained fever > 38oC
Night sweats
Loss of > 10% body weight in 6 months

10. Staging of lymphoma
Contiguous spread
from one
lymphoid group to
the other groups
(Classically occurring in
Hodgkin lymphoma,
may not be true in other
lymphomas)

11. Malignant lymphomas
Clinical evaluation of a lymphoma patient
1. History
2. Physical examination
lymph node areas
liver and spleen
3. Blood count, bone marrow examination
4. Radiologic imaging of abdomen and
thorax, including positron emission
tomography computed tomography,
computed tomography, or magnetic
resonance imaging

12. Histopathologic evaluation of lymphomas
1. Histology
2. Immunophenotyping to determine the cell
lineage of the lymphoma
3. Molecular genetics for confirmation of
cellular lineage
Rearrangement studies of the following
genes
T-cell receptor gene for T-cell lymphomas
Immunoglobulin heavy chain gene for B-
cell lymphomas
Malignant lymphomas

13. Malignant lymphomas
Pathological classification
World Health Organization (WHO)
1. Histological appearance
2. Immunophenotyping of lymphoma cells
3. Cytogenetic / molecular features
All three features are needed for
appropriate classification of lymphomas

14. Malignant lymphomas
Old classification
Non-Hodgkin
lymphoma
Hodgkin
lymphoma

15. Malignant lymphomas
B cell lymphomas
Hodgkin
lymphoma
T cell
lymphomas
NK cell
lymphomas
Pathological classification

16. Malignant lymphomas
Lymphoma dissemination
1. Typically through the lymphatics -
Hodgkin lymphoma
2. Haematogenous spread very
frequent in other types of
lymphomas
3. Local infiltration into different
organs

17. Malignant lymphomas
Treatment
1. Chemotherapy: the main treatment for all types
of lymphomas
2. Radiotherapy: for localized lymphomas, as well
as for consolidation after chemotherapy
3. Purine analogues
4. Targeted therapy with monoclonal antibodies,
against antigens expressed on the surface of
lymphoma cells forms an important part in the
treatment of lymphomas (B-cell lymphomas and
T-cell lymphomas express different antigens
and therefore require different antibodies)
5. Haematopoietic stem cell transplantation for
high risk cases, or for relapsed lymphomas
6. Other novel treatment modalities

18. Malignant lymphomas
Prognosis
1. International prognostic index
Tumor stage
Serum LDH level
Number of extranodal disease sites
Performance status
Age

19. Malignant lymphomas
Prognosis
2. Histological type
High grade
Low grade
B cell / T cell / NK cell
3. Intensity of chemotherapy used

20. Malignant lymphomas
B cell lymphomas
Histological features
High grade B cell lymphomas
Diffuse large B cell
Burkitt lymphoma
Low grade B cell lymphoma
follicular lymphoma
small lymphocytic lymphoma
Chronic B cell lymphoproliferative disease
chronic lymphocytic leukaemia

21. Malignant lymphomas
Treatment of B-cell lymphomas
General principles
1. A monoclonal antibody against a B-cell
specific antigen + chemotherapy is the
standard
2. Currently, rituximab and obinutuzumab
are the two monoclonal antibodies
against CD20 that are used
3. An anthracycline-containing
chemotherapy regimen, such as CHOP,
is the standard

22. Malignant lymphomas
Treatment of B-cell lymphomas
High-grade lymphomas
intensive chemotherapy may be curative
Low-grade lymphomas
options include the use of
anthracycline-containing regimens
purine analogue containing regimens
Maintenance treatment with monoclonal
antibody

23. Malignant lymphomas
Treatment of B-cell lymphomas
Haematopoietic stem cell transplantation (HSCT)
1. Autologous HSCT is a standard treatment for
patients with relapsed lymphoma
2. The source of HSC is most commonly from
the peripheral blood, and sometimes from the
bone marrow
3. Patients with marrow involvement initially
may be considered candidates for allogeneic
HSCT

24. Malignant lymphomas
Hodgkin lymphoma
1. Less common in the Chinese population
2. Overall prognosis very good and most
patients are curable.
3. Treatment is a combination of chemotherapy
with or without radiotherapy
4. Monoclonal antibody (against CD30) is used
in relapsed patients
5. PD1 blockade is another treatment strategy
6. Autologous HSCT is also a standard
treatment for relapsed patients

25. Malignant lymphomas
NK cell lymphomas
1. Derived from natural killer cells
2. Affect the nose as the main site
3. Associated with Epstein Barr
virus
4. Highly aggressive tumour with
an unfavourable prognosis
5. Found predominantly in Asians,
and are very rare in Western
patients

26. Malignant lymphomas
T cell lymphomas
1. Uncommon lymphoma
2. Prognosis variable
3. Treatment is similar to B cell
lymphomas
4. A particular type is associated with
5. infection with HTLV-1, which is
prevalent in Japan and Taiwan

27. Malignant lymphomas
Treatment of NK and T cell lymphomas
1. No consensus on what the best treatment
strategy is
2. Most treatment approaches are still
experimental
3. Early use of autologous HSCT may be
beneficial in T-cell lymphomas
4. For NK-cell lymphomas, L-asparaginase
containing regimens may be more
effective

28. Malignant lymphomas
Conclusions
1. Lymphomas can affect both lymph nodes and sites
outside lymph nodes
2. Lymphoma classification is complex and needs to be
done in specialized centres
3. Lymphoma treatment is mainly chemotherapy,
supplemented by radiotherapy
4. Monoclonal antibodies have an important role in the
treatment of B-cell lymphomas, and are of increasing
importance in the treatment of other lymphomas
5. Haematopoietic stem cell transplantation may be useful
for some patients
6. “Novel” treatment modalities helpful in selected patients
7. Histological classification is important in the diagnosis
and treatment of patients.
8. Different lymphomas have different treatment strategies
and prognosis.