limfoma-PPT-monce

7/27/2019 limfoma-PPT-monce

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Limfoma


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Limfoma......

Neoplasma yang berasal dari jaringanlimfoid, biasanya menyebabkanlimfadenopati

Limfoma sebagai perluasan klonal sel-sel pada fase perkembangan sel

tertentu


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LymphomaWhere They Begin

Limfoma adalahkanker sistem limfatik

lymphatic system Pembuluh limfatik Limfonodus (ketiak,

leher, limfa, tonsil andsumsum tulang)


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Lymphatic System

American Medical Association


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Lymphomas Where They Begin

Sistem limfatik adalah sistem pertahananutama tubuh terhadap infeksi

Limfosit (B-cell and T-cell) Dibawa melalui sistem limfatik dan berperan

pada pertahanan tubuh terhadap inteksi Limfosit dibawa melalui pembuluh limfe serta

pembuluh darah, sehingga sel kanker dapatbermula di satu nodus dan menyebar ketempat lain di dalam tubuh


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B-cell development

stemcell

lymphoidprogenitor

progenitor-B

pre-B

immatureB-cell

memoryB-cell

plasma cellDLBCL,FL, HL

ALL

CLL

MM

germinalcenter B-cell

maturenaiveB-cell


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Lymphoma classification(2001 WHO)

B-cell neoplasms precursor mature

T-cell & NK-cell neoplasms precursor mature

Hodgkin lymphoma

Non-HodgkinLymphomas


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A practical way to think of lymphomaCategory Survival of

untreatedpatients

Curability To treat or not to treat

Non-Hodgkin

lymphoma

Indolent Years Generallynot curable

Generallydefer Rx if

asymptomatic Aggressive Months Curable in

someTreat

Very

aggressive

Weeks Curable in

some

Treat

Hodgkinlymphoma

All types Variable months toyears

Curable inmost

Treat


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Evaluasi limfoma harus tepat karenaterapi bervariasi sesuai stadium,gambaran histologis, dan lokasi

Limfoma bisa disembuhkan jikaditangani secara tepat


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Limfoma Non Hodgkin...


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Non- Hodgkins Lymphoma Two main types of Non- Hodgkins

Lymphoma:

B-Cell and T-Cell Lymphomas

B-Cell lymphomas (80%) T-Cell lymphomas (15%)


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B-Cell Cancers


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Causes and Risk Factors

The Exact causes are still unknown Higher risk for individuals who:

Exposed to chemicals such as pesticides or solvents

Infected w/ Epstein-Barr Virus Family history of NHL (although no hereditary

pattern has been established) Infected w/ Human Immunodeficiency Virus

(HIV)

Lymphoma.org


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CERVICAL ADENOPATHY manifestasi yangpaling sering muncul pada limfoma non-Hodgkin 10% occur in head and neck extranodal sites

Waldeyers ring Paranasal sinuses Nasal cavity Larynx Oral cavity

Salivary glands Thyroid Orbit


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Regional Lymph Node of the Head & Neck Region


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Waldeyers Ring


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Symptoms

Painful Swelling of lymph nodes locatedin the neck, underarm and groin.

Unexplained Fever Night Sweats Constant Fatigue Unexplained Weight loss Itchy Skin

Cancer Sourcebook


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Sites and Presenting Symptoms > 50% of extranodal H&N lymphomas

Waldeyers ring tonsils > nasopharynx > base of tongue

Lymphomas are usually submucosal , differing ingross appearance from ulcerative squamous cellcancer

1/3 H&N lymphomas extralymphatic sites paranasal sinuses, nasal cavity, salivary glands, oral

cavity, larynx, and orbit


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Sinus lymphomas symptoms of sinusitis,with diplopia and exophthalmos occurring withmore bulky disease

Nasal cavity lymphomas obstructivesymptoms and nasal bleeding

Oral cavity lymphomas local swelling,pain, and ulcers

Laryngeal lymphomas hoarseness,dyspnea, and dysphagia

Salivary gland lymphomas a parotidmass, facial nerve involvement is rare

Sites and Presenting

Symptoms


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Primary lymphoma of the thyroid gland 5% to 10% of all thyroid cancers 75 % a rapidly enlarging thyroid mass or symptoms

of hoarseness and dysphagia

Orbital lymphoma Usually complain of orbital swelling exophthalmos

Changes in vision, proptosis, ptosis, and pain Visual fields unaffected, and the fundi are usually

benign Patients with conjunctival disease palpable pink

mass in the conjunctiva


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Sites and Presenting

Symptoms Others symptoms

15% of patients neck adenopathy as a

presenting complaint 12% of patients systemic symptoms of

fever, night sweats, or weight loss

20% of patients multiple sites of involvement in the head and neck


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Clinical manifestations Variable

severity: asymptomatic to extremely ill time course: evolution over weeks, months, or

years Systemic manifestations

fever, night sweats, weight loss, anorexia, pruritis

Local manifestations lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated


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Diagnosis

X-Rays CT scans Magnetic Resonance Imaging (MRI) Biopsy Lymphangiogram

Pictures of the lymphatic system taken w/x-ray after a special dye is injected toilluminate lymph nodes and vessels


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Diagnosis requires an

adequate biopsy Diagnosis should be biopsy-proven

before treatment is initiated

Need enough tissue to assess cells andarchitecture open bx vs core needle bx vs FNA


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Diagnosis and Histologic

Classification OPEN BIOPSY Fine-needle aspiration Immunohistochemical stains

Discriminating lymphoma from undifferentiated or anaplastic neoplasms

Differentiate a benign lymphoid infiltrate from alymphoma on light microscopy

Methods : antikeratin antibodies carcinoma anti-S-100 protein antibodies melanoma pan-leukocyte antibodies lymphoma better performed on fresh rather than on formalin-fixed

tissue


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Diagnosis and Histologic

Classification Most non- Hodgkins lymphomas are T-cell or

B-cell neoplasms

A panel of T-cell antigens can differentiate T-celllymphomas from hyperplasia A single class of light chains (i.e., kappa or

lambda) is expressed in B-cell lymphomas;

Nodes with hyperplasia admixture of the twoclasses


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Histological classification Two major groups:1. Low-grade (indolent) NHL indolent course, do not

always need treatment, but cannot be cured by mostpresent approaches. Examples : the follicular lymphomasand CLL.

2. High-grade (aggressive) NHL: aggressive clinicalcourse and, if untreated, are rapidly fatal. In a fraction of these NHL, cure is achieved with chemotherapy.Examples are Burkitts lymphomas and diffuse large B-cell lymphomas (DLBCLs).


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Histologic Classification


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Clinical AssessmentDiagnosis (site) Symptoms Staging tests (for all sites )

Tonsil Tonsillar swelling, throat pain Pathologic review and complete physicalexamination

Nasopharynx Cervical mass, obstruction Indirect laryngoscopy and complete blood countBase of tongue Foreign body sensation Liver function testsParanasal sinus Exophthalmos, diplopia, pain HIV test (positive risk factors) and chest radiographNasal cavity Obstruction, rhinorrhea CT or MRI of head and neck

Upper gastrointestinal series with small bowelfollow- through (Waldeyers ring)

Oral cavity Local swelling, painLarynx Hoarseness, dyspnea, dysphagia CT scan of abdomenSalivary glands Mass Lymphangiogram (if available)Thyroid Mass Lumbar puncture (paranasal sinus)Orbit Swelling, pain, proptosis, ptosis Bone-marrow biopsy

HIV, Human immunodeficiency virus; CT, computed tomography; MRI, magnetic resonance imaging.


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Other complications of

lymphoma bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal

cord, ureters) pleural/pericardial effusions, ascites


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Emergencies

Diagnosis Emergency Complication

Oropharyngeal/ Airway obstruction Respiratory distress

laryngeal lymphomaTumor lysis syndrome Hyperuracemia, Cardiac arrhythmiashyperkalemia, renal failure, deathhyperphosphatemia,hypocalcemia

Neutropenic fever Sepsis Shock, deathLeptomeningeal Cord compression, Paralysis, comalymphoma confusion, cranial

neuropathies


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Non- Hodgkins Lymphoma

Staging Stage is the term used to describe the extent

of tumor that has spread through the body( Iand II are localized where as III and IV areadvanced.

Each stage is then divided into categories A,B, and E A: No systemic symptoms B: Systemic Symptoms such as fever, night

sweats and weight loss E: Spreading of disease from lymph node to

another organ


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Ann Arbor Staging System

Designation Characteristic

Stage I Involvement of a single lymph node region (I) or of a singleextralymphatic organ or site (IE)

Stage II Involvement of two or more lymph node regions on the sameside of the diaphragm (II) or localized involvement of anextralymphatic organ or site and of one or more lymph noderegions on the same side of the diaphragm (IIE)

Stage III Involvement of lymph node regions on both sides of thediaphragm (III)

Stage IV Diffuse or disseminated involvement of one or moreextralymphatic organs or tissues with or without lymph node

involvementSymptoms A Absence of systemic symptomsB Unexplained fever, night sweats, or weight loss of more than 10% body

weightE Spreading of disease from lymph node to another organ

From ref 2.


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Stage I Stage II Stage III Stage IV

Staging of lymphoma

A: absence of B symptomsB: fever, night sweats, weight loss


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Treatment Options

Chemotherapy Radiation Bone Marrow Transplantation Surgery Immunotherapy

Using the bodies own immune system combinedwith material made in a lab with monoclonalantibodies (targeted therapy)


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ManagementPATHOLOGISTS, RADIOLOGIST,OTOLARYNGOLOGISTS

Outcome depends histologic, stage, and primarysite

Treatment choices depend on histologic subtype andstage


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Management

Histology grade Stage Treatment options

Low I, II Involved-field XRTIII, IV CVP, chlorambucil,

observationIntermediate I,II CHOP X 3- XRT- CHOPX 3,

CHOPX 3- XRTIII, IV CHOP or other combination

chemotherapy

High I IV Combination chemotherapy

XRT, irradiation; CVP, cyclophosphamide + vincristine + prednisone;CHOP,cyclophosphamide + doxorubicin + vincristine + prednisone .


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Radiotherapy

200-cGy daily fractions Total dose of 3,000 to 4,000 cGy (low-

grade) and 4,900 to 5,000 cGy(intermediate-grade) Optimal treatment of lymphoma

linear accelerator that produces photonswith an energy of 4 MeV or more

Fields type of tumor, location, andindividual patient anatomy


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Chemotherapy

CVP Cyclophosphamide, 400 mg/m2 orally (p.o.) days 1 5 Vincristine, 1.4 mg/m2 intravenously (i.v.) day 1

Prednisone, 100 mg/m2 p.o. days 1 5 Repeat every 21 days CHOP

Cyclophosphamide, 750 mg/m2 i.v. day 1 Doxorubicin, 50 mg/m2 i.v. day 1

Vincristine, 1.4 mg/m2 i.v. day 1 Prednisone, 50 mg/m2 p.o. days 1 5 Repeat every 21 days

Other regimens have added bleomycin or high-dosemethotrexate to these combinations


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Low-grade Stage I or II

Lymphomas Radiation therapy Most trials have not shown an advantage to

adding chemotherapy


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Intermediate-grade Stage I or II

Lymphomas Stage I disease

disease-free survival rate at 5 years is

between 80% and 100% overall survival rate between 95% and

100%

Stage II disease 5-year disease-free survival rate isbetween 75% and 80%

overall survival rate is between 75% and90%


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Intermediate-grade Stage III or

IV Lymphomas Chemotherapy is the primary treatment

CHOP

The complete response rate 50% to 85% At 5 years, disease-free survival rates of 30% to60% and overall survival rates of 35% to 70%

Regimens incorporating other agents

methotrexate or bleomycin Radiation therapy to consolidate areas of

bulky disease or for urgent treatment of airway obstruction


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Intermediate-grade Stage III or

IV Lymphomas Advanced-stage, intermediate-grade disease who failprimary chemotherapy High-dose therapy with stem-cell or bone marrow

transplantation

Several-fold higher doses of chemotherapy and whole-body irradiation

For certain favorable subgroups of patients withrecurrent disease (i.e., chemotherapy-sensitive disease,age less than 60 years, good performance status), mostpatients may enter a sustained remission


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High-grade Lymphomas Lymphoblastic lymphoma T-cell lymphoma

Young patients as a mediastinal mass Spreads rapidly to the CNS and bone marrow (poor) Treatment :

combination chemotherapy

Diffuse small noncleaved cell lymphoma (Burkitts or non- Burkitts types) Combination chemotherapy high-dose cyclophosphamide,

doxorubicin, vincristine, prednisone, high-dose methotrexate,and intrathecal methotrexate

During the first few days at risk for tumor lysis syndrome . about 65% of patients are alive at 2 years


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Thyroid Lymphomas Stages IE and IIE thyroid lymphoma

Radiation therapy Extended-field irradiation, includes cervical and mediastinal

nodes

The disease-free survival rate 75% at 5 years Poor prognostic factors :

Bulky tumor, extracapsular extension, fixation, andretrosternal involvement

Three or six cycles of CHOP chemotherapy inaddition to irradiation Patients with stages III or IV :

Chemotherapy depends on the histology subtype


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Complications of Radiation Therapy

Complication Signs Treatment

Mucositis Oral pain, ulcers MouthwashXerostomia Dry mouth, caries, infections Sialagogues, oral

pilocarpineHypothyroidism Fatigue, constipation, cold Thyroid replacement

intoleranceNeutropenia Fever Antibiotics, GCSFNausea Vomiting AntiemeticsCardiomyopathy Heart failure Discontinue drug digoxin,

diureticNeuropathy Peripheral neuropathy, Discontinue drug

hoarseness, constipation,

GCSF, granulocyte colony stimulating factor.


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Complications of Chemotherapy Myelosuppression

Neutropenia or thrombocytopenia mostpotentially life-threatening toxic effect

Fever complete blood count

neutropenic hospitalization with systemicantibiotics Alopecia vincristine, cyclophosphamide &

doxorubicin Nausea and vomiting doxorubicin and

cyclophosphamide Hemorrhagic cystitis, as dysuria or hematuria cyclophosphamide

Cardiac dysfunction Doxorubicin, > 550 mg/m2 or lower dose levels in elderly patients, cardiac history,

mediastinal irradiation


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Complications of Chemotherapy VINCRISTINE

Neurologic peripheral neuropathy, constipation, andileus, hoarseness from vocal cord dysfunction

METHOTREXATE Mucositis, gastrointestinal ulcerations, and hematologic

toxicities Ameliorated by following high-dose methotrexate with

leucovorin rescue Excreted through the kidneys renal function

BLEOMYCIN Skin erythema, rash, and hyperpigmentation Pulmonary toxicity interstitial fibrosis measurement of

carbon monoxide diffusion capacity


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After completion of therapy, patients should bereassessed regularly Evaluation of all prior sites of disease and a physical

examination

Chest radiograph Plain film of the abdomen (if a lymphangiogram was

performed) Complete blood count Liver function tests Appropriate imaging studies to assess new

complaints


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Survival Rates

Survival Rates vary widely by cell typeand staging.

1 Year Survival Rate: 77%

5 Year Survival Rate: 56%

10 Year Survival Rate: 42%Cancer.org


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Terapi Target (TargetedTherapy)

Terapi target didefinisikan sebagai obatatau molekul untuk membunuh sel tumor melalui interaksi target yang terdapat padasel ganas.

Terapi target ditujukan bagaimana secaraselektif melawan molekul pada permukaansel dan jalur signal metabolik sel ganas.

dapat memisahkan sel normal selanjutnyamengurangi toksisitas dan memperbaikikualitas hidup.


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Targeted therapy pada LNH

Normal B cells at almost every stage of development express a membrane-

spanning protein called CD20. The function of CD20 is not fully

understood, although it is suspected to

play roles in calcium regulation and Bcell development.


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CD20 in cancer cellsCD20 is an attractive therapeutic target for reasons: It is expressed by nearly 90 percent of all B cell

non-Hodgkin lymphomas. although CD20 is present on most normal B cells,

the stem cells that give rise to B cells do notexpress the protein. This it means that B cellsdamaged by a CD20-targeted therapy can bereplaced.

CD20 is not present on any other cells in thebody, which makes it less likely that drugstargeting this protein will damage other tissuesand organs.
http://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=CDR0000046598&version=Patient&language=Englishhttp://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=CDR0000046598&version=Patient&language=English


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Targeting CD20

Several monoclonal antibodies have beendesigned to target CD20 on lymphoma cells.These include rituximab, tositumomab, andibritumomab tiuxetan. The mechanisms of these therapeutic antibodies vary, but all of them bind to CD20 on the surface of both

normal and cancerous B cells.


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