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Lymphomas: Part II Non-Hodgkin’s lymphoma (NHL) Lymphomas: Part II Non-Hodgkin’s lymphoma (NHL)

Lymphomas: Part II Non-Hodgkin’s lymphoma (NHL) - PowerPoint Presentation

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Lymphomas: Part II Non-Hodgkin’s lymphoma (NHL) - PPT Presentation

NonHodgkins lymphoma NHL is a term covering all lymphoproliferative system malignancies except Hodgkins lymphoma The disease is rare in subject under 30 years of age and incidence increase with age Around twothirds of all cases are diagnosed in people over 60 years ID: 913401

cell lymphoma response therapy lymphoma cell therapy response nhl chemotherapy high treatment follicular relapse symptoms patients grade stage disease

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Slide1

Lymphomas: Part II

Slide2

Non-Hodgkin’s lymphoma (NHL)

Non-Hodgkin’s lymphoma (

NHL) is a term covering all

lymphoproliferative

system malignancies except Hodgkin's lymphoma . The disease is rare in subject under 30 years of age and incidence increase with age . Around two-thirds of all cases are diagnosed in people over 60 years .

Natural history

Lymphomas can be classified by degree of aggressiveness:

1

-

Low grade or indolent

كسول

lymphomas

: in which patients may remaining asymptomatic for many years . (untreated survival, measured in years) .

2

-

High-grade lymphoma

is an aggressive and often rapidly fatal condition . (untreated survival measured in months)

Slide3

Etiology:

Congenital and acquired immunodeficiency

is the most clearly defined factor known to increase NHL risk.' Immunosuppressant drugs following transplantation lead to a significantly increased (30-50 times) risk of NHL.

The risk of NHL in people infected with

HIV i

s more than 100 times that of the general population. Infectious organisms such as

Epstein-Barr virus

,

Helicobacter pylori

and

hepatitis C virus

have all been thought to play a part in the development of NHL.

There are data pointing to a number of

occupational

,

dietary

, e

nvironment

al and other risk factors that may help to explain the rising incidence of NHL .

Slide4

Symptoms

NHL usually presents with a painless lump in a lymph node area (most commonly the neck, but also the

axillae

or groin) . Weight loss, fever and night sweats (known as B-symptoms ) present in about 20% of patients with non-Hodgkin's lymphoma

.

Patients without these symptoms are classified as category A (without symptoms).

There may be upper abdominal pain from

hepatosplenomegaly

.

Spread of the disease is

haematogenously

(via the blood ) and so extra nodal sites may be involved .

Extra nodal involvement is more common in NHL than HL , with involvement of bone marrow, gut , lung, skin, brain,…..

.

Other features relate to the site of origin of an extra-nodal lymphoma

.

For example,

Mesenteric or gastrointestinal involvement can cause nausea, vomiting, obstruction, abdominal pain, palpable abdominal mass, or gastrointestinal bleeding.

Bone marrow involvement can cause symptoms related to anemia,

neutropenia

(

reduction of

neutrophils

)

, or

thrombocytopenia(low platelet count) .

whereas lymphoma of the central nervous system may cause symptoms of raised intracranial pressure with vomiting, headache and fits .

Slide5

Laboratory Finding :

Laboratory examination may reveal

anaemia

,

a raised

ESR

& a raised Plasma lactate

dehydrogenase

(

LDH)

level

Diagnosis and Staging

:

The diagnosis of NHL is established by

histological examination of lymph node biopsy sample

. (

or biopsy of involved

extranodal

tissue

) .

The staging system for non-Hodgkin's lymphoma is the same as that used for Hodgkin's disease and its main use is to distinguish localized stage I and II disease from the disseminated stage III and IV disease

Slide6

classification

The most recent classification of lymphoma is the World Health Organization/revised European-American Lymphoma classification which is

1-Precusor B-cell neoplasm

2-Mature (peripheral) B-cell

neoplasms

3-Precursor T-cell neoplasm

4-Mature (peripheral) T-cell and natural-killer

neoplasms

Diffuse Large B-Cell Lymphoma

(DLBCL ), an aggressive lymphoma, represents

around 30 %

and

B-cell

follicular lymphoma ,

an indolent (non-aggressive) lymphoma represents around 22 % of all cases of lymphoma Both of them are within the second group

(

Mature (peripheral) B-cell

neoplasms

)

All other types of lymphoma have a frequency of less than 10 %, therefore this lecture will focus on

Diffuse Large B-Cell Lymphoma (DLBCL )

&

follicular lymphoma.

Slide7

Desired outcome

:

The primary treatment goals for non-Hodgkin's lymphoma are to relieve symptoms and, whenever possible, cure the patient of disease without causing unacceptable toxicity .

Treatment

A-Indolent NHL (

Low grade )

:

Follicular lymphoma is the most common indolent lymphoma

. Treatment strategies are summarized for

follicular Lymphoma

as an example of how to treat indolent lymphoma as follow:

Low grade :

Stag I/II -----

Radiation -----

Relapse

Stage III/IV either:

-asymptomatic -----

watch and wait .

- symptomatic ----

chlorambucil

----

Relapse ----

Second line chemotherapy

  Most patients relapse (median response duration is about 2 years), at least 20% of complete responders will remain in remission for about 10 years .

Slide8

Early stage follicular lymphoma treatment

Involved-field radiotherapy (

Radiation to a single field ), when given alone, can cure early stage (I or II) follicular lymphoma and this remains the standard of care in this patient group

Advanced Follicular Lymphoma(stage III/ IV):

1-

Asymptomatic patients

at diagnosis can be followed with " Watch and wait " policy in which therapy is delayed until the patient experiences systemic symptoms or disease progression such as rapidly progressive or bulky

adenopathy

, anemia, thrombocytopenia, or disease in threatening sites such as the orbit or spinal cord . The median time until

chemotherapy

is required is about 3 years

2-

Symptomatic patients

:

Oral

alkylating

agents (

chlorambucil

), given either alone or in combination, have been the mainstay of treatment for follicular lymphoma

Slide9

A-Single agent therapy

:

Oral

alkylating

agents,

chlorambucil

, or

cyclophosphamide

, are the mainstay of treatment. These single agents are as effective as combination regimens and produce minimal toxicity, but

secondary

acute myelogenous leukemia (AML) is a concern.

(AML)

is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. i.e., a drop in red blood cells, platelets, and normal white blood cells

Therefor

Fludarabine

and

cladribine

(

It is a

purine

analog, which interferes with DNA synthesis)

produce high response rates without secondary AML, but they are more

myelosuppressive

(i.e.,

bone marrow suppression, characterized by a decrease in blood cell production).

 

Slide10

B-

Combination chemotherapy

:

Combination chemotherapy such as

CVP

(

cyclophosphamide

,

vincristine

,

prednisone

) or

CHOP

(

cyclophosphamide

,

hydroxydaunomycin

(

Adriamycin

,

a new antitumor antibiotic

),

Oncovin

(

vincristine

),

prednisone

) gives a higher response and longer time to first relapse than the use of single agent

alkylators

alone, but does not improve overall survival . Therefore patients in whom a more rapid response is desired,

multiagent

chemotherapy such as (CVP) or (CHOP) may be used .

Slide11

C-

Rituximab

:

Rituximab

is a

monoclonal

antibody ( that binds specifically to the antigen CD20 expressed on B- lymphocytes, and it cause

lysis

of B lymphocytes . NHL of B-cell origin expresses CD20 in greater than 90% of cases

.

Rituximab

has become one of the most widely used therapies for follicular lymphoma.

Rituximab

was initially used as salvage therapy and is also being used as first-line therapy, either alone or combined with CVP (R-CVP ) or CHOP (R-CHOP ) .

Rituximab

has the advantage of

being suitable for retreatment therapy

and, interestingly, produces a

longer duration of remission after the second course than after the first course

.

Adverse effects are usually infusion related, especially after the first infusion of

rituximab

. Adverse effects include fever, chills, respiratory symptoms, fatigue, headache,

pruritus

, and

angioedema

. Patients should receive acetaminophen, 650 mg, and

diphenhydramine

, 50 mg, 30 minutes before the infusion

Slide12

D-

Radioimmunotherapy

:

Novel strategies for treatment of low-grade lymphomas include the combination of monoclonal antibodies directed against CD20 with a radioactive moiety attached. Two such entities are now approved by (FDA):

ibritumomab-yttrium90 (

Zevalin

®)

is a monoclonal antibody to which a radioactive isotope (either

yttrium-90

or indium-111) is added.

and

tositumomab

iodine131(

Bexxar

®

) .

They have the advantage of delivering radiation to tumor cells expressing the CD20 antigen and to adjacent tumor cells that do not express it. They have the disadvantage of damaging adjacent normal tissue (e.g., bone marrow) .

They are licensed for the treatment of CD20-positive follicular B-cell non-Hodgkin's lymphoma,

unresponsive to

rituximab

or which is relapsed

and is being evaluated as first-line therapy in combination with CHOP .

Slide13

B-High-grade (or aggressive) lymphoma treatment

Diffuse Large B-Cell Lymphoma

(DLBCL ) is the most common high-grade lymphoma . Treatment strategies are summarized for

DLBCL

as an example of how to treat High-grade lymphoma

Intermediate/ high grade either:

Stage I/II

-----

Short course combined chemotherapy x 2

+ involved field radiation

¦

Relapse / No response

¦

Salvage chemotherapy (Either)

¦

Good response -----

Consolidation high dose

تقوية

+

Autologous

ذاتي

stem cell transplantation

Or Relapse /No response -----

Palliative

مسكن

therapy

Stage III/IV

-----

combined chemotherapy x 6

¦

Relapse /No response

¦

Salvage chemotherapy (Either)

¦

Good response -----

Consolidation high dose

+

Autologous

stem cell transplantation

Or Relapse /No response -----

Palliative therapy

 

Slide14

Salvage Therapy for Aggressive Lymphoma

 

Salvage therapy is more likely to induce response if the response to initial chemotherapy was complete (

chemosensitivity

) than if it was less than complete (

chemoresistance

) .

High-dose chemotherapy with

autologous

HSCT is the therapy of choice for younger patients with

chemosensitive

relapse .

Usually Salvage regimens incorporate drugs not used as initial therapy.

Slide15

Commonly used regimens include

DHAP

(

dexamethasone

, high-dose

cytarabine

[

Ara

-C], and

cisplatin

[

Platinol

]),

ESHAP

(

etoposide

,

methylprednisolone

[

Solumedrol

], high-dose

cytarabine

[

Ara

-C], and

cisplatin

[

Platinol

]), and

MINE

(

mesna

(

Mesna

is used therapeutically to reduce the incidence of

haemorrhagic

cystitis and

haematuria

when a patient receives

ifosfamide

or

cyclophosphamide

for cancer chemotherapy.

,

ifosfamide

(is a nitrogen mustard

alkylating

agent

,

mitoxantrone

[

Novantrone

,

"antitumor antibiotic."

], and

etoposide

a DNA toxin

).

None is clearly superior to the others.

ICE

(

ifosfamide

,

carboplatin

(

interact with DNA to interfere with DNA repair).

, and

etoposide

) appears to be better tolerated than

cisplatin

-containing regimens, especially in elderly adults.

Rituximab

is being evaluated in combination with many salvage regimens.