Transcript LYMPHOMA Hodgkin`s Disease Non

LYMPHOMA
Hodgkin`s Disease
Non-Hodgkin`s Disease
Acibadem University
Acibadem Medical Faculty
Paediatrics Department
Ertugrul Eryilmaz MD
Assistant Professor Paediatrics
Lymph System
Lymphoma may affect any of the parts of the
lymph system. Most commonly, patients first
notice an enlargement of lymph nodes - usually
in the neck, groin or armpits.
Lymphomas can occur in other organs as well.
This is because small amounts of lymph and
lymph tissue pass through practically all organs
in the body in order that white blood cells can
reach them to control infections.
RES
++Timus
Lymphoid tissue
Two types of lymphoid tissue exist:
– Central (bone marrow and thymus) and
– Peripheral (blood, spleen,liver, lymph node,
and mucosa-associated).
Within central lymphoid tissue, cells arise
and differentiate into mature lymphocytes;
they then migrate into peripheral lymphoid
tissues and recirculate throughout the
body
DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; HL Hodgkin Lymphoma, MM Multiple Myeloma ALL Acutel
lymphocytic lymphoma; CLL Chronic Lymphoblastic Lymphoma
CLL
stem
cell
mature
naive
B-cell
germinal
center
B-cell
memory
B-cell
lymphoid
progenitor
MM
progenitor-B
ALL
pre-B
immature
B-cell
DLBCL,
FL, HL
plasma cell
ALL
CLL
Lymphomas
MM
naïve
B-lymphocytes
Lymphoid
progenitor
AML
Hematopoietic
stem cell
Myeloid
progenitor
Plasma
cells
T-lymphocytes
Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Proto-Oncogenes / Suppressor
Genes
Similar to most human cancers, the
genetic lesions involved in non-Hodgkin
lymphoma include activation of protooncogenes and disruption of tumour
suppressor genes
Lymphoma
Lymphoma is the third most common
cancer in children, with an annual
incidence of 13-14 per million children.
The two broad categories of lymphoma,
Hodgkin disease and non-Hodgkin
lymphoma (NHL), have such different
clinical manifestations and treatments that
they are considered separately.
age adjusted incidence/100,000/yr
Incidence of lymphomas in comparison
with other cancers in Canada
70
60
lung
colorectal
breast
50
40
30
20
NHL
10
Hodgkin
lymphoma
0
1985
1990
1995
Year
2000
Hodgkin lymphoma
Thomas Hodgkin
(1798-1866)
Hodgkin Disease
Epidemiology
Three forms of Hodgkin disease have been identified in
epidemiologic studies: a childhood form (≤ 14 yr of age),
a young adult form (15-34 yr of age), and an older adult
form (55-74 yr of age).
Hodgkin disease accounts for about 5% of cancers in
persons younger than 15 yr of age and for about 15% in
persons 15-19 yr of age,
In industrialized countries the highest rate is in
adolescents and young adults, in contrast to developing
countries, where the highest rate is in younger children.
Hodgkin Disease
Epidemiology
The role of Epstein-Barr virus (EBV) is supported by
serologic studies and the frequent presence of EBV
genome in biopsy material.
Males predominate in patients younger than 10 yr of age
at diagnosis, with roughly equal gender incidence in
adolescence.
Pre-existing immunodeficiency, either congenital or
acquired, increases the risk of developing Hodgkin
disease.
A genetic predisposition or a common exposure to the
same etiologic agent could account for an apparent
increased risk in twins and first-degree relatives ranging
from 3- to 7-fold.
0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
incidence/100,000/annum
Age distribution of new Hodgkin
lymphoma cases in Canada
6
5
4
3
2
1
0
Age (years)
Pathogenesis
The Reed-Sternberg cell, a large cell (1545 μm in diameter) with multiple or
multilobulated nuclei, is considered the
hallmark of Hodgkin disease
There is now general agreement that the
Reed-Sternberg cell arises from germinal
center B-cells in most cases.
Histologic subtypes
lymphocyte predominant,
nodular sclerosing
mixed cellularity
lymphocyte depleted.
Most cases previously classified as lymphocyte
depleted are now considered to represent highgrade non-Hodgkin lymphoma.
Pathognomonic
Lymphocyte Predominant
Reed Sternberg & CD20 (+)
Mixed Cellularity
Clinical Manifestations
Painless, firm, cervical, or supraclavicular lymphadenopathy is the
most common presenting sign.
Inguinal or axillary lymphadenopathy sites are uncommon areas of
presentation.
An anterior mediastinal mass is often present and can rapidly
disappear with therapy
Clinically detectable hepatosplenomegaly is rarely encountered.
Depending on the extent and location of nodal and extranodal
disease, patients might present with symptoms and signs of airway
obstruction, pleural or pericardial effusion, hepatocellular
dysfunction, or bone marrow infiltration (anemia, neutropenia, or
thrombocytopenia).
Nephrotic syndrome is a rare but recognized presenting
manifestation of Hodgkin disease
Some causes of mediastinal
Masses in adults.
Some Causes of Mediastinal
Masses in Children
Anterior
Ectopic thyroid
Lymphoma
Sarcoma
Teratoma
In thymus:Cyst Histiocytosis Histoplasmosis Normal thymus Thymoma
Middle
Bronchogenic cyst
Cardiac tumor
Cystic hygroma
Lymphadenopathy
Lymphoma
Pericardial cyst
Vascular abnormalities
Posterior
Esophageal duplication
Meningomyelocele
Neuroenteric abnormalities
Neurogenic tumors
SYMPTOMS
Systemic symptoms considered important in staging
– Unexplained fever
– Weight loss
– Drenching night sweats.
Less common non-prognostic significance are
–
–
–
–
pruritus,
lethargy,
anorexia,
pain that worsens after ingestion of alcohol.
Because of the impaired cellular immunity, concomitant tuberculous or
fungal infections may complicate Hodgkin disease and predispose to
complications during immunosuppressive therapy.
In the pre-vaccine era varicella-zoster infections occurred at some time
during the course of the disease in about 30% of cases.
Diagnosis
Any patient with persistent, unexplained
lymphadenopathy unassociated with an obvious
underlying inflammatory or infectious process should
have a chest radiograph to identify the presence of a
mediastinal mass before undergoing node biopsy.
Formal excisional biopsy is preferred over needle biopsy
to ensure that adequate tissue is obtained,
Hodgkin disease is rarely diagnosed with certainty on
frozen section. Ideally, a portion of the biopsy specimen
should be frozen and stored to allow for additional
studies.
Modified Ann Arbor Staging
System for Hodgkin Disease*
STAGE I Involvement of a single lymph node region or of a single
extralymphatic organ or site
STAGE II Involvement of two or more lymphoid regions on the same side of
the diaphragm; or localized involvement of an extralymphatic organ or site
and of one or more lymph node regions on the same side of the diaphragm
STAGE III Involvement of lymph node regions on both sides of the
diaphragm, which may be accompanied by localized involvement of an
extralymphatic organ or site or by splenic involvement
STAGE IV Diffuse or disseminated involvement of one or more
extralymphatic organs or tissues, with or without associated lymph node
enlargement
*Stages are further categorized as: A or B, based on the absence or
presence, respectively, of systemic symptoms of fever and/or weight loss
Bulky disease, based on mediastinal mass larger than one third thoracic
diameter; lymph node masses ≥10 cm in diameter and/or four or more nodal
regions involved.
Staging of lymphoma
Stage I
Stage II
Stage III
Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss
Studies Necessary for Clinical
Staging of Hodgkin Disease
Measurement of palpable lymph nodes, liver, and spleen
Complete blood cell count
Erythrocyte sedimentation rate,
Serum ferritin,
Serum copper
Liver function tests
Chest radiograph with measurement of mediastinal ratio
Chest CT with contrast medium enhancement
Neck CT if high cervical nodes palpable
Abdominal CT or MRI Gallium scan
Bone marrow biopsy with advanced disease or "B" symptoms
Bone scan with elevated serum alkaline phosphatase level and/or
bone pain
Treatment
Because of concern about late effects, treatment of children in North
America and Europe has evolved from primary treatment with
extended-field radiation therapy to use of multiagent chemotherapy
as the cornerstone of treatment, supplemented in selected cases by
relatively low-dose involved-field irradiation (2,000-2,500 cGy).
Treatment is largely determined by disease stage, patient's age at
diagnosis, the presence or absence of "B" symptoms, and the
presence of hilar lymphadenopathy and/or bulky nodal disease.
Although there is not yet general agreement on their definitions,
three risk groups have been identified.
Favorable presentations include stages I and IIA.
Intermediate presentations include stages I, IIB (with symptoms,
bulky disease, or hilar lymphadenopathy), and stage IIIA.
Unfavorable presentations include stages IIIB and IV.
Chemotherapy
The chemotherapy regimens in current use are based on
– MOPP (nitrogen mustard [Mustargen], vincristine [Oncovin],
procarbazine, and prednisone), or
– ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and
dacarbazine),
– or variations and/or combinations of the two together with
additional active agents such as etoposide and methotrexate.
– As originally conceived, a minimum of six cycles of
chemotherapy was given with significant cumulative
toxicity, including
second malignancies,
sterility,
and cardiac
and pulmonary dysfunction.
– The long-term toxicity is determined by the total dose of the
agents.
EORTC risk factors in localised
disease
Favourable
Patients must have all features:
Clinical stage 1 and 2
Maximum of three nodal areas involved
Age younger than 50 years
Erythrocyte sedimentation rate (ESR) less than 50 mm/h without B
symptoms or
ESR less than 30 mm/h with B symptoms
Mediastinal/thoracic ratio less than 0·35
Unfavourable
Patients have any features:
Clinical stage 2 with involvement of at least four nodal areas
Age older than 50 years
ESR greater than 50 mm/h if asymptomatic or ESR greater than 30
mm/h if B
symptoms
Mediastinal/thoracic ratio greater than 0·35
UNFAVORABLE
PRESENTATIONS
Chemotherapy, based on the same regimens
used in early stage disease, is considered the
primary treatment for patients with advanced
disease, but the role of radiation is still under
study.
Because the cure rate with conventional drug
combinations, with or without radiation therapy,
is only 60-70%, newer and more aggressive
regimens have been developed and are now in
clinical trials.
RELAPSE
Patients who suffer relapse after initial treatment
with radiation alone or after an initial remission
of more than 12 mo after chemotherapy alone or
combined modality therapy usually respond to
additional chemotherapy or radiation or both.
Those who never achieve remission or who
suffer relapse after an initial remission of less
than 12 mo after chemotherapy or combined
modality therapy have a poorer prognosis and
are candidates for myeloablative chemotherapy
and autologous stem cell or bone marrow
rescue.
Prognosis
Most treatment programs result in disease-free survival
rates of more than 60%, with overall cure rates greater
than 90% in those with early stage disease and more
than 70% in more advanced cases.
All newly diagnosed cases in children and adolescents
should be treated with curative intent; this is consistently
and effectively achieved with combined modality therapy.
The choice of regimen is then selected on the basis of
risk category and observed or anticipated long-term
complications. Elimination of routine staging laparotomy
and splenectomy avoids concerns about surgical
morbidity and postsplenectomy infections.
Classical Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) results from malignant clonal
proliferation of lymphocytes of T-, B-, or indeterminate cell origin.
In the United States, NHL occurs with an annual incidence of 10.5
per million white and 7.3 per million black children younger than 20
yr of age.
In equatorial Africa, 50% of childhood cancers are lymphomas, a
result of the very high incidence of Burkitt lymphoma and possibly
related to the immunosuppressive effects of malaria. Unlike that of
Hodgkin disease, the incidence of NHL increases steadily
throughout life.
In some situations there is overlap with acute lymphoblastic or B-cell
leukemia. Patients with lymphoblastic NHL and more than 25%
lymphoblasts in the bone marrow are arbitrarily classified and
treated as if they had acute lymphoblastic leukemia, whereas
patients with B-cell ALL are treated similarly to patients with Burkitt
lymphoma even if no extramedullary disease is present.
0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Incidence/100,000/annum
Age distribution of new NHL cases in
Canada
100
80
60
40
20
0
Age (years)
Pathogenesis
EBV infection has a major role in the
pathogenesis of Burkitt lymphoma. The EBV
genome is present in tumor cells in 95% of
"endemic" cases in equatorial Africa compared
with 15% in "sporadic" cases in the United
States.
How EBV contributes to the pathogenesis of
Burkitt lymphoma remains unclear.
Congenital or acquired immunodeficiency also
predisposes to the development of NHL.
Epidemiologic studies have also implicated
pesticide exposure as a possible risk factor.
Classification
Most cases of NHL in children are high-grade,
diffuse neoplasms.
Three histologic subtypes are recognized:
– lymphoblastic, usually of T-cell origin;
– small non-cleaved cell lymphoma (SNCCL), with
Burkitt and non-Burkitt subtypes and of B-cell origin
– large cell lymphoma (LCL), with diffuse and
anaplastic subtypes and of T-, B-, or indeterminate
cell origin.
The diagnosis and classification of childhood NHL requires
considerable hematopathologic expertise and adequate
diagnostic tissue, both fresh and frozen.
Chromosomal Translocations
Different chromosomal translocations are specific for
some histologic subtypes and involve various protooncogenes, resulting in malignant transformation through
a variety of mechanisms.
In SNCCL (Burkitt type), one of three chromosomal
translocations [t(8;14), t(8;22), t(2;8)] results in
approximation of the MYC proto-oncogene on
chromosome 8 to a regulatory region of one of the
immunoglobulin chain genes, resulting in dysregulation
of MYC;
In anaplastic LCL, fusion of the NPM gene on
chromosome 5 with the ALK gene on chromosome 2
leads to formation of a chimeric protein that can
influence cell growth and proliferation.
Clinical Manifestations
Presenting signs and symptoms vary with disease site and extent,
and these in turn differ with histologic subtype.
Lymphoblastic NHL often presents as an intrathoracic tumor, usually
a mediastinal mass, and is associated with dyspnea, chest pain,
dysphagia, pleural effusion, and superior vena cava syndrome.
Cervical or axillary lymphadenopathy is present in up to 80% of
patients at diagnosis. Primary involvement of bone, bone marrow,
testis, or skin is not uncommon. The central nervous system (CNS)
may also be involved.
SNCCL presents as an abdominal tumor in 80% of U.S. cases in
patients with abdominal pain or distention, bowel obstruction,
change in bowel habits, intestinal bleeding, or, rarely, intestinal
perforation. Other sites include CNS, bone marrow, and peripheral
lymph nodes. Jaw involvement occurs in less than 20% of U.S.
cases, compared with 70% of younger patients in equatorial Africa.
LCL occurs in many sites, including the abdomen and mediastinum.
Extramedullary sites include skin, bone, and soft tissues. CNS
involvement is rare, in contrast to SNCCL and lymphoblastic NHL.
LABORATORY FINDINGS
Pretreatment Studies for Staging Pediatric NonHodgkin Lymphoma
– Complete blood cell count
– Serum electrolytes,
– Uric acid, lactate dehydrogenase, creatinine, calcium,
phosphorus
– Liver function tests
– Chest radiograph and chest CT if abnormal
– Abdominal and pelvic ultrasonography and/or CT
– Gallium scan and/or bone scan
– Bilateral bone marrow aspirate and biopsy
– Cerebrospinal fluid cytology
Investigations done before initiation of
treatment
Essential procedures
A full history, recording growth rate, symptoms
present, performance status
A detailed physical examination, with special
attention to all node-bearing areas including
Waldeyer’s ring
Adequate surgical biopsy specimen, allowing
immunophenotyping and examined by a skilled
pathologist
Investigations done before initiation of
treatment
Laboratory procedures:
Full blood count, including erythrocyte sedimentation
rate
Serum lactate dehydrogenase, calcium, uric acid,
proteins and electrophoresis, alkaline phosphatase
Assessment of renal and liver function
Radiological studies:
Chest radiograph
Thoracic and abdominal-pelvic CT scan
Bone-marrow aspirate and trephine, to include molecular
genetic analysis if available
Optional procedures, depending on
clinical picture
2 microglobulin
Endoscopy, eg, for gastric MALT lymphoma
Plain radiographs, bone scan, or MRI
Positron electron tomography (PET)
Head or spinal MRI for neurological symptoms
Cerebrospinal fluid analysis in patients at risk
Laboratory findings
Laboratory findings vary, depending on sites or
organs involved.
– Elevated serum uric acid levels and other features of
tumor lysis syndrome often complicate the
presentation of SNCCL.
– Elevated serum level of lactate dehydrogenase is a
measure of tumor burden and may occur with any
NHL subtype.
– A normal CBC does not preclude marrow
involvement.
– CT or MRI of the chest or abdomen or both provides
key information on disease extent.
– Surgical staging is not necessary.
Symptoms of non-Hodgkin lymphoma
needing urgent referral
Lymphadenopathy (>1 cm persisting for 6 weeks)
Hepatosplenomegaly
Three or more of the following symptoms:
Fatigue
Night sweats
Weight loss
Itching
Breathlessness
Bruising
Recurrent infection
Bone pain
Diagnosis
Prompt tissue diagnosis and staging is important
because of the rapid growth rate of lymphomas,
especially SNCCL.
To ensure adequate tissue for accurate diagnosis and
subtyping, multiple needle biopsy specimens or a large
wedge of tumor should be obtained.
Several studies are necessary to accurately stage the
disease and provide baseline measurements of organ
function before treatment is instituted
In cases with airway compromise, potential for
anesthetic complications, and no easily accessible tissue
to sample, empirical therapy may be started using
corticosteroids.
An algorithm for evaluation and treatment of children with an anterior mediastinal mass.
Hammer G B Anesth Analg 2001;92:1449-1464
©2001 by Lippincott Williams & Wilkins
Diagnosis
The St. Jude staging system defines tumor
extent, which is important for designing
treatment.
Stage I applies to localized disease, stage II to
regional disease (except for mediastinal tumors,
which are designated stage III), stage III to
extensive disease, and stage IV to disseminated
(CNS and/or bone marrow) disease. Elevated
levels of serum lactic dehydrogenase (>500 U/L)
correlate with tumor mass and have proved
useful for stratifying therapy intensity.
St. Jude Staging System for
Childhood Non-Hodgkin
Lymphoma
STAGE I A single tumor (extranodal) or single anatomic area
(nodal), with the exclusion of mediastinum or abdomen.
STAGE II A single tumor (extranodal) with regional node
involvement. Two or more nodal areas on the same side of the
diaphragm. Two single (extranodal) tumors with or without regional
node involvement on the same side of the diaphragm. A primary
gastrointestinal tract tumor, usually in the ileocecal area, with or
without involvement of associated mesenteric nodes only, which
must be grossly (>90%) resected.
STAGE III Two single tumors (extranodal) on opposite sides of the
diaphragm. Two or more nodal areas above and below the
diaphragm. Any primary intrathoracic tumor (mediastinal, pleural, or
thymic). Any extensive primary intra-abdominal disease.
STAGE IV Any of the above, with initial involvement of central
nervous system and/or bone marrow at time of diagnosis.
Staging of lymphoma
Stage I
Stage II
Stage III
Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss
Treatment and Prognosis
Surgical excision of localized intra-abdominal tumors
often precedes the diagnosis of NHL and should always
be attempted, if feasible.
In this and other situations, multiagent chemotherapy is
the primary treatment.
Tumor lysis syndrome (i.e., high serum potassium, uric
acid, and high phosphorus with low calcium levels)
frequently complicates initial treatment of disseminated
disease. Appropriate hydration with addition of sodium
bicarbonate to produce dilute alkaline urine,
administration of allopurinol, and correction of electrolyte
abnormalities are essential to minimize this lifethreatening complication.
In contrast to HD, second malignancies and infertility
have not been major problems in long-term survivors of
NHL
EARLY-STAGE NHL
Unlike HD, NHL is considered a disseminated disease
from the time of diagnosis. Even patients with apparently
localized and resected disease require chemotherapy.
Patients with stage I/II NHL, irrespective of histologic
subgroup, are effectively treated with six cycles of
COMP (cyclophosphamide, vincristine [Oncovin],
methotrexate, and prednisone) or three cycles of COPA
(substituting doxorubicin for methotrexate) followed by 6
mo of mercaptopurine and methotrexate or,
In the case of T-cell lymphoblastic NHL, an acute
lymphoblastic leukemia-like regimen. About 90% of
cases are cured with these regimens. The emphasis now
is on decreasing morbidity of therapy for these children
while maintaining the high cure rate.
ADVANCED-STAGE NHL
Patients with stage III/IV NHL are best treated
with therapy based on the histologic subtype.
Lymphoblastic lymphoma is treated with
intensive chemotherapy regimens, generally of 2
yr duration and consisting of multiple
chemotherapeutic agents given in cycles or a
regimen based on those used for high-risk acute
lymphoblastic leukemia.
Cranial radiation, intrathecal chemotherapy,
and/or high-dose methotrexate are important for
prevention of CNS disease.
Early relapse require cytoablativechemotherapy,
and allogenic bone marrow transplantation.
ADVANCED-STAGE NHL
SNCCL is treated with relatively short-duration (3-6 mo) intensive
chemotherapy regimens, including an alkylating agent (usually
cyclophosphamide) coupled with other active systemic agents
(vincristine, prednisone, methotrexate, cytarabine, etoposide, and/or
doxorubicin) and intrathecal therapy, which produces survival rates
of more than 90% in localized and 70-80% in those with
disseminated disease.
If relapse occurs, it becomes evident in the 1st yr after diagnosis
and is often rapidly progressive and relatively resistant to additional
therapy, especially in patients with stage IV disease.
LCL is treated with intensive multiagent chemotherapy regimens
similar to those used for lymphoblastic lymphoma, which have
produced long-term survival rates of 50-70% in those of T-cell origin.
For B cell-derived LCL, short, intensive regimens as outlined earlier
for SNCLL have produced 6-yr event-free survival as high as 95%.
Extranodal lymphomas
Extranodal lymphomas in general should be
treated as for nodal disease.
Aggressive lymphomas are usually treated with
combined chemoradiotherapy, producing an
80% 5-year survival, a 20–30% improvement on
treatment with radiotherapy alone.
Certain extranodal lymphomas present special
clinical management problems.
Gastric lymphoma of MALT type
Mucosa-associated lymphatic tissue, or "MALT"
lymphoma
Although MALT-type marginal-zone lymphomas arise at
other sites (such as salivary gland, lung, and thyroid),
gastric MALT lymphomas are uniquely related to
previous infection with Helicobacter pylori.
Eradication with appropriate antibiotics results in
regression of the lymphoma in three-quarters of patients,
Although fewer than half achieve sustained molecular
remission.The 10-year survival is about 90%, although
transformation to diffuse large B-cell lymphoma can
happen.
Lymphoma of the central nervous
system
Primary lymphoma of the central nervous system is an
aggressive tumour (usually of diffuse large B-cell type)
arising in brain, leptomeninges, or eye.
Its prevalence has risen strikingly in the
immunocompetent population.
Traditionally, radiotherapy was the treatment of choice,
but tumour recurrence was common, and chemotherapy
(with high-dose methotrexate-based regimens),
combined with irradiation, has strikingly enhanced
average survival to up to 5 years.
However, late neurotoxic effects are a typical
complication of this approach, and chemotherapy alone
is being tested.
Testicular lymphoma
Although rare, primary testicular lymphoma is
the most frequent testicular malignancy in men
older than age 60 years.
Pathology is usually of diffuse large B-cell type,
and despite apparently localised presentation,
prognosis is worse than with most other sites
with the same histological findings.
A high frequency of central nervous system
relapse has been noted, so much so that
prophylactic intrathecal chemotherapy has been
advocated in addition to CHOP and adjuvant
radiotherapy.
New approaches
High-dose chemotherapy
For aggressive lymphoma in first remission
For refractory or relapsed aggressive high-grade
lymphoma
For indolent lymphoma
Allogeneic stem-cell transplantation
Radiolabelled monoclonal antibody treatments
Vaccine treatments
Radiolabelled monoclonal
antibody treatments
Rituximab is a chimeric human-murine IgG1 monoclonal antibody that binds
specifically to the B-cell surface antigen CD20
The glycosylated protein consists of the constant regions of human IgGs
combined with the variable region from murine IgGs, and is produced by
Chinese hamster ovary cells in suspension culture.
The antibody induces both complement-mediated and antibodydependent
cytotoxic effects on CD20-positive cells.
It has also been reported to induce apoptosis and sensitise chemoresistant
human lymphoma cell lines to cytotoxic chemotherapy.23–25 The antibody
is well tolerated and its main toxic effect is either haematological
(thrombocytopenia and neutropenia) or infusion-related.
Prevalence of human antichimeric antibody is less than 10%.26–28 It has
important single-agent efficacy, giving remission rates of 40–50% in the
treatment of relapsed indolent lymphoma,
Now received UK National Institute for Clinical Excellence approval for
patients who have failed standard chemotherapy.
Unusual Non-Hodgkin Lymphomas
Mycosis fungoides
Mycosis fungoides is a rare, persistent, very slow-growing non-Hodgkin
lymphoma.
Most people who develop it are older than 50.
It originates from mature T lymphocytes and first affects the skin.
Mycosis fungoides starts so subtly and grows so slowly that it may not be
noticed initially. It causes a long-lasting, itchy rash—sometimes a small area
of thickened, itchy skin that later develops nodules and slowly spreads.
In some people, it develops into a form of leukemia (Sézary syndrome). In
other people, it progresses to the lymph nodes and internal organs. Even
with a biopsy, doctors have trouble diagnosing this disease in its early
stages. However, later in the course of the disease, a biopsy shows
lymphoma cells in the skin.
The thickened areas of skin are treated with a form of radiation called
electron beam or with sunlight and corticosteroids applied to the skin..
On average, people live 7 to 10 years after the diagnosis is made, but
survival varies widely depending on how far the cancer has spread.
Treatment does not cure the disease, but it slows it down even further.
SEZARY SYNDROME/Erythema
Unusual Non-Hodgkin Lymphomas
Burkitt's lymphoma
Burkitt's lymphoma is a very fast-growing non-Hodgkin lymphoma that
originates from B lymphocytes.
Burkitt's lymphoma can develop at any age, but it is most common in
children and young adults, particularly males.
Unlike other lymphomas, Burkitt's lymphoma has a specific geographic
distribution: It is most common in central Africa and rare in the United
States.
Infection with Epstein-Barr virus is associated with Burkitt's lymphoma.
It is more common in people who have AIDS.Burkitt's lymphoma grows and
spreads quickly, often to the bone marrow, blood, and central nervous
system.
When it spreads, weakness and fatigue often develop.
Large numbers of lymphoma cells may accumulate in the lymph nodes and
organs of the abdomen, causing swelling. Lymphoma cells may invade the
small intestine, resulting in blockage or bleeding.
The neck and jaw may swell, sometimes painfully.
To make the diagnosis, doctors do a biopsy of the abnormal tissue and
order procedures to stage the disease.
Indolent (Slow-Growing, Low
Grade) Lymphomas
Slow-growing lymphomas are subdivided into numerous B-cell and
T-cell subtypes, for example:
B-cell
Small lymphocytic / pro-lymphocytic lymphoma (SLL)
Follicular lymphoma (few large cells)
Lymphoplasmacytoid lymphoma
Marginal zone lymphoma
T-cell
Large granular lymphocyte leukemia
Adult T-cell leukemia/lymphoma (ATL/L )
Mycosis fungoides/Sézary Syndrome
INDOLENT LYMPHOMA
A type of lymphoma that tends to grow and spread slowly, and has
few symptoms. Also called low-grade lymphoma. lymphoma,
usually takes several years to develop.
Follicular lymphoma is typically a slow-growing, or indolent, form of
non-Hodgkin lymphoma.
This cancer, which accounts for roughly 20 to 30 percent of all nonHodgkin
It usually appears in a lumpy, or nodular pattern, within lymph nodes
throughout the body.
Often, the first sign of follicular lymphoma is a painless swelling in
the neck, armpit or groin caused by enlarged lymph nodes.
Some people also report loss of appetite and fatigue.
Doctors sometimes suggest watchful waiting for people with indolent
lymphoma. People with indolent lymphoma may not have problems
that require cancer treatment for a long time.
Waldenstrom’s Macroglobulinemia
Waldenstrom’s macroglobulinemia (also known as
lympho-plasmacytic lymphoma or immunocytoma) is a
rare, slow-growing B-cell lymphoma that occurs in less
than 2 percent of people with NHL.
Waldenstrom’s is characterized by a high level of a
protein called immunoglobulin M (IgM) in the blood.
These high levels of IgM can cause a thickening of the
blood (hyperviscosity), resulting in symptoms such as
nosebleeds, headaches, dizziness and blurring or loss of
vision
Angioimmunoblastic T-cell
lymphoma
Angioimmunoblastic T-cell lymphoma is a rare,
aggressive (fast-growing) T-cell lymphoma that accounts
for between 1 percent and 2 percent of all NHL cases.
Symptoms include high fever, night sweats, skin rash
and some types of autoimmune disorders, such as
autoimmune hemolytic anemia (AIHA) and immune
thrombocytopenic purpura (ITP), in which the body does
not recognize its own cells.
As a result of these autoimmune disorders, the body
makes antibodies against and destroys its own cells and
tissues, such as platelets (in the case of ITP) and red
blood cells (in the case of AIHA).
Further Listening 
http://www.lymphoma.org/site/pp.asp?c=b
kLTKaOQLmK8E&b=6300123
Contains Podcasts and webcasts about
lymphoma
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