hodgkins and nonhodgkins lymphoma 1232532099923357 1

8/2/2019 Hodgkins and Nonhodgkins Lymphoma 1232532099923357 1

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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



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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



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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



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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



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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


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)


Relapse (N = 791)

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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)

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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)


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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)


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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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hodgkins and nonhodgkins lymphoma 1232532099923357 1

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