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Hodgkins andnon-Hodgkins Lymphoma
A/Prof Graham YoungSenior Staff Specialist
Institute of HaematologyRoyal Prince Alfred Hospital
Sydney
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Tonights Talk
What is Lymphoma?
Do we know what causes it?
Hodgkins Lymphoma Non-Hodgkins Lymphoma
Whats New?
Questions and discussion Resourses and Information
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WHAT IS LYMPHOMA?
LYMPHOMA
is the term applied to a heterogeneouscollection of diseases characterised bythe presence of malignant lymphoid cells.
i.e.Cancer of the Lymphatic System
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LYMPHOMA
Traditionally 2 main Types of Lymphoma
Non-Hodgkins Lymphoma Hodgkins Lymphoma
6th Most Common Cancer Much less common
4.1% of cancers in Australia 0.5% of cancers
3500 new cases / year 400 new cases / year
Incidence increases with age Peak incidence inMany different subtypes Adolescence and >50
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What causes Lymphoma?
In most cases we do not know
It is likely that several factors are important
e.g. Genetic predisposition
plus infection (bacteria or virus)
plus chemicals
plus ???? But in some cases we know some risk factors
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RISKFACTORS
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Haemopoiesis
erythroid myeloid megakaryocytic
B lymphoid T lymphoid
AML
Lymphoma/
CLL
ALL
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Types of lymphocytes(defined by surface antigens, in vitro function, types of illness when lacking)
B cells: humoral immunity
antibody productionT cells: cellular immunity
cytotoxicity against virus, fungus
B cell help
Most lymphomas are of B cell type (80%)
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B cell malignancies
Pre-B acute lympho-
blastic leukaemia
B cell lymphoma Chronic lympho-
cytic leukaemia
Multiple myeloma
Progressive B lymphocyte maturation
Bone marrow
Lymph node,
lymph, blood,
bone marrow
Lymph node,
lymph, blood,
bone marrowBone marrow
Lymphoid stem cell Maturing B cell
many stages
Mature B cell Plasma cell
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How does lymphoma present?
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 toconfirm 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
small cell large cell
Indolent Aggressive
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Hodgkins Lymphoma - Staging
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PET (Positron Emission Tomography) Scan
xxxxxx xxx
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Hodgkins lymphoma (HL)
Accounts for ~ 30% of all malignant lymphomas
Composed of two different disease entities:Lymphocyte-predominant Hodgkins (LPHL),making up ~ 5% of cases and
Classical HL, representing ~ 95% of all HLs.
A common factor of both HL types is that neoplasticcells constitute only a small minority of the cells inthe affected tissue, often corresponding to < 2% ofthe total tumour
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Features of Classical Hodgkin Lymphoma
Fatal disease with 90% of untreated patients dyingwithin 2 to 3 years
With chemotherapy, >80% of patients suffering from
cHL are cured.Pathogenesis of cHL is still largely unknown.
cHL nearly always arises and disseminates in lymph
nodes
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Hodgkins Lymphoma - Management
We have come a long way
1 Prognostic or Risk Factorallocation of treatment groups
2 Staging (PET and CT)
3 Intensive treatment strategiese.g. BEACOPP
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Hodgkins Lymphoma - Progress
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Hodgkins Lymphoma - Advanced Disease
< late 1960s Radiotherapy
1966 MOPP 50 % cure
Mechlorethamine,
Oncovin (Vincristine),Procarbazine,
Prednisone
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Background to current recommendedFirst line therapy
1982 ABVD(doxorubicin, bleomycin, vinblastine and dacarbazine)
partial non-cross resistance with MOPPsalvage 20 % of MOPP failures
1990s 5 randomised trials:
alternating monthly cycles of MOPP/ABVDsuperior to MOPP
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BEACOPP
Developed as COPP / ABVD variant by GHLSG with
same dosages (except vincristine and procarbazine) ina shorter 3 week cycle):
COPP / ABVD BEACOPP
Cyclophosphamide Y YVincristine Y YProcarbazine Y Y
Prednisone Y YDoxorubicin Y YBleomycin Y YVinblastine Y N etoposide
Dacarbazine Y N instead
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BEACOPP-dose escalated + acceleratedregimen+ RT vs COPP/ ABVD +RT
(HD 9 Trial) 5th interim analysisA B C
COPP /ABVD Sd. BEACOPP esc BEACOPP p (A vs C)
CR % 84 88 96
5y FFTF% 67 75 89
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BEACOPP-dose escalated + acceleratedregimen+ RT vs COPP/ ABVD +RT(HD 9 Trial) 5th interim analysis
Side effects from escalated BEACOPP
Acute haematological manageablebut
3 % mortality
100 % infertility in men and women(cyclophosphamide and procarbazine)
Premature menopause in most women > 25 y.o.
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Hodgkins Lymphoma Management Algorithm
BIOPSYTissue
STAGINGCT/PET
PROGNOSTIC FACTORS
EARLY STAGE(Favourable) ADVANCED STAGE(Unfavourable)ADVANCED STAGE(Favourable)EARLY STAGE(Unfavourable)
ABVD (3) + IFRT ABVD (6) + IFRT ABVD (6 8) BEACOPP (6-8)
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Second Malignant Neoplasms Among Long-Term Survivors ofHodgkins Disease: A Population-Based Evaluation Over 25 Years
Graa M. Dores, Catherine Metayer et al,JCO, 20, (2002): 3484-3494
Data from 32,591 HD patients (1,111 25-year survivors) reported to 16population-based cancer registries in North America and Europe (1935to 1994) were analyzed.
2153 second cancers [O/E] = 2.3; 95% [CI] = 2.2 to 2.4)including 1,726solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) reported
Cancers of the lung (Obs = 377; O/E = 2.9)digestive tract (Obs = 376; O/E = 1.7)female breast (Obs = 234; O/E = 2.0)
25 years after HD diagnosis, the risk of developing a solid tumor was 21.9%.
Increased risks for all solid tumors taken together were observedafter therapy with either radiation alone (Obs = 632; O/E = 2.3;
chemotherapy alone (Obs = 211; O/E = 1.7;combined-modality therapy (Obs = 149; O/E = 3.1;
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Hodgkins Lymphoma - Fertility
Sperm counts are often low before therapy
MOPP causes high incidence of infertility
ABVD rarely causes permanent infertility
and currently sperm cryopreservation isnot recommended (Draft Lymphomaguidelines)
BEACOPP / High dose CT less certain If fertility recovers sperm quality is good
No excess of congenital abnormalities with
prior chemotherapy
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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/highlyaggressive 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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Randomised intergroup trial of first linetreatment for patients 60 years with diffuse
large B-cell non-Hodgkins lymphoma (DLBCL)with a CHOP-like regimen with or without the
anti-CD20 antibody MabThera early stopping
after first interim analysis
M Pfreundschuh, L Trmper, D Ma, A sterborg,R Pettengell, M Trneny, L Shepherd, J Walewski,
P-L Zinzani, and M Loeffler for the MabTheraInternational Trial (MInT) Group
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
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CD20+
DLBCL1860 yearsIPI 0,1
Stages IIIV,I with bulk
6 x CHOP-like+ 3040 Gy (Bulk, E)
6 x CHOP-like
+ MabThera+ 3040 Gy (Bulk, E)
Randomisation
MInT: trial design
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
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Median age (years) 48 47Histology (%)
DLBCL 96 95
other 4 5
Bulky disease (%) 52 49
B-symptoms (%) 29 27
Extranodal involvement (%) 33 32
Chemon=165
R-Chemon= 161
MInT Interim Analysis:patient characteristics
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
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Chemon=165
R-Chemon= 161
MInT Interim Analysis:patient characteristics
Ann Arbor stage (%)I 19 19II 55 60III 12 12IV 15 9
ECOG performance status (%)
0,1 99 1002,3 1 -
LDH >UNL (%) 29 34
IPI age-adjusted (%)0 43 451 57 55
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
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MInT: adverse events*
Percentageo
fpatients
5753
40 39
116 8 8
2 3
*Reported toxicity
CTC Grades 3 and 4
Chemotherapy
MabThera +
chemotherapy
60
50
40
30
20
10
0
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
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p
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MInT: conclusions
MabThera plus CHOP or CHOP-like chemotherapy inyoung patients with low-risk DLBCL results in
higher remission rates
reduced progression rates
prolonged time to treatment failure
increased survival rates no additional toxicity
Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)
S O
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ANNUAL NUMBERS OFBLOOD AND MARROW TRANSPLANTS
WORLDWIDE
1970-2002
NUMB
EROFTRANSPLANTS
YEAR
1970 1975 1980 1985 1990 1995
Autologous
Allogeneic
2000
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
40,000
45,000
1
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..
..
............... ......
.
..... . .
..
..........
................ ......... ..
.................
....
..
.. ........ ...............
. .........................
..... ......
.
.......... .......... .. ....
.. ...........
......
..
.. ...
..... ........ .
.
..
......
..
.
..
. ...
. ...
........
............. ........
..........
. ........................
. ............ .........
.............
.
.
.
.
.. .... .. .
.
.
.
... . .
.
.
.
..
. ... ... ... .
2
LOCATION OF CENTERS PARTICIPATINGIN THE IBMTR / ABMTR
2003
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INDICATIONS FOR BLOOD AND MARROWTRANSPLANTATION IN NORTH AMERICA
2002
TRANSPLANTS
4,500
0
500
1,000
1,500
2,000
Allogeneic (Total N = 7,200)
Autologous (Total N = 10,500)
2,500
3,000
4,000
3,500
BreastCancer
NHLMultipleMyeloma
AML ALL CMLMDS /Other
Leukemia
CLL OtherCancerNeuroblastoma
HodgkinDisease
Non-MalignantDisease
7
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PROBABILITY OF SURVIVAL AFTERAUTOTRANSPLANTS FOR HODGKIN DISEASE, 1996-
2001
PROBABILITY,%
100
0
20
40
60
80
YEARS
P = 0.0001
0 1 2 3 4 65
CR1 (N =226)
CR2+ (N =733)
Never in remission (N = 823)
Relapse (N = 1,744)
33
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PROBABILITY OF SURVIVAL AFTERAUTOTRANSPLANTS FOR FOLLICULAR NON-
HODGKIN LYMPHOMA, 1996-2001
PROBABILITY,%
100
0
20
40
60
80
YEARS
P = 0.0009
0 1 2 3 4 65
CR1 (N =174)
CR2+ (N =
322)
Never in remission (N = 418)
Relapse (N = 791)
34
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PROBABILITY OF SURVIVAL AFTER HLA-IDENTICALSIBLING MYELOABLATIVE TRANSPLANTS FOR
FOLLICULAR NON-HODGKIN LYMPHOMA, 1996-2001
PROBABILITY,
%
100
0
20
40
60
80
YEARS
P = NS
0 1 2 3 4 65
CR1-3 (N =
79)
Never in remission (N =138)
Relapse (N = 193)
35
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PROBABILITY OF SURVIVAL AFTERAUTOTRANSPLANTS FOR DIFFUSE LARGE CELL
LYMPHOMA, 1996-2001
PROBABILITY,
%
100
0
20
40
60
80
YEARS
P = 0.0001
0 1 2 3 4 65
CR1 (N =438)
CR2+ (N =651)
Relapse (N = 1,443)
Never in remission (N = 986)
36
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PROBABILITY OF SURVIVAL AFTER HLA-IDENTICALSIBLING MYELOABLATIVE TRANSPLANTS FORDIFFUSE LARGE CELL LYMPHOMA, 1996-2001
PROBABILITY,
%
100
0
20
40
60
80
YEARS
P = NS
0 1 2 3 4 65
CR1-3 (N =
56)
Relapse (N = 144)
Never in remission (N = 133)
37
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TAKE HOME MESSAGES
1 Lymphoma is the term applied to acollection of diseases characterised bya malignant proliferation of lymphoid
cells. 2 Optimal management relies onaccurate histological classification andanatomical and biological staging.
3 Many patients can be cured of theirlymphoma.
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