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
Download Presentation The PPT/PDF document "Lymphomas: Part II Non-Hodgkin’s lymph..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Lymphomas: Part II
Slide2Non-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)
Slide3Etiology:
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 .
Slide4Symptoms
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 .
Slide5Laboratory 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
Slide6classification
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.
Slide7Desired 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 .
Slide8Early 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
Slide9A-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).
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 .
Slide11C-
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
Slide12D-
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 .
Slide13B-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
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.
Slide15Commonly 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.