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LYMPHOMAS

Cell-mediated immunity
APC

T-cells Suppressor cells MACs Cytotoxic cells Helper cells

Lymphokines

B-cells

Tc Activated macrophages NK cells K-cells (ADCC)

heavy,light chain gene rearrangement

surface immunoglobulin

Pre pre-B

pre-B cell

early B

mature B

cortex

mantle zone deep cortical area(paracortex follicle

medullary cords

T-cell receptor gene rearrangement

pre-T cell

large cortical thymocyte

small cortical thymocyte

medullary thymocyte

B-Cell Cancers

Chronic lymphocytic

Prolymphocytic leukemia

LGL leukemia

leukemia

Hairy cell disease Sezary cells Lymphoblasts Plasma cells

Small lymphocytic lymphoma

Follicular small cleaved cell lymphoma

ALL

Plasma cell Lymphoma and Chronic Lymphoid disorders Leukemia


Hodgkins

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

Behavior
Indolent these lymphomas grow slowly. The majority of NHLs are considered indolent. Indolent lymphomas are generally considered incurable with chemotherapy and/or radiation therapy. Aggressive these lymphomas have a rapid growth pattern. This is the second most common form of NHL and are curable with chemotherapy. Very Aggressive these lymphomas grow very rapidly. They account for a small proportion of NHLs and can be treated with chemotherapy. Unless treated rapidly, these lymphomas can be life threatening.

Chronic Lymphoid Disorders


Lymphoma
Hodgkin's Nondisease Hodgkin's lymphoma

Plasma cell disorders (PCD)


Multiple myeloma Other PCD

Chronic lymphoid leukemia


B cell T cell NK cell

CLL

CLL variants

Treatment Options
Chemotherapy Radiation Bone Marrow Transplantation Surgery Bortezomib (Velcade) Immunotherapy
Using the bodies own immune system combined with material made in a lab.

Case : Bulky Lymphoma


70 years old; bulky mass in the neck Biopsy - diffuse large cell NHL
CD20+

B symptoms - fever/sweats CT chest/abd - stage III disease LDH elevated

New Tests
Cytogenetics
FISH = fluorescent in situ hybridization

Immunoglobulin gene mutational status


Germline Somatic mutations

Flow cytometry

Treatment Modalities for Non-Hodgkins Lymphoma


Surgery - usually biopsy; occasionally resection Chemotherapy - multiple regimens Radiation therapy - local Rx Immunotherapy - rituximab - 1998 Radioimmunotherapy - new modality

Rituximab : structure
Chimeric anti-human CD20 monoclonal antibody
VH VL C C1

Murine variable regions Human constant region Human constant Fc region

Variable region: murine IgG1 kappa anti-CD20 Constant region: human IgG1 heavy chain and kappa light chain

Rituximab - Mechanisms of Action


Antigen Fc region
Antibody

Granules

Fc receptor (FcgRIII)

NK Cell

B cell

Lysis
H2O, ions, granzymes

Granules release perforins, granzymes, cytokines (eg, IFN-g) Pores (perforin)

Treatments for CLL


No advantage to early treatment for the asymptomatic early stage patient Chlorambucil Fludarabine Fludara - Cytoxan - Rituxan

Rai Staging of Chronic Lymphocytic Leukemia (CLL)


Stage
Criteria
Lymphocytosis (>15,000/mm3) Lymphadenopathy Splenomegaly Hepatomegaly Anemia (hemoglobin <11 g/dL) Thrombocytopenia (<100,000/mm3)

II

III

IV

+ +/-

Idiotype Vaccines
Idiotype Rescue

Tumor Biopsy

by Cell Fusion or Molecular Approach

Vaccine Production

Immunization KLH Carrier Protein Id Adjuvant Tumor Id Protein

Case 1 continued
Treatment options:
Observation Oral alkylating agents - chlorambucil CVP Rituxan

Radioimmunotherapy
Properties 90Yttrium
Half-life Energy emitter Path length 64 hours Beta (2.3 MeV) 90 5 mm

131Iodine
192 hours Gamma (0.36 MeV) Beta (0.6 MeV) 90 0.8 mm

Naked antibody

Radiolabeled antibody

Radioimmunotherapy
High response rate - 80% Moderate complete remission rate - 30% Long term responses are possible Excellent patient tolerance Myelosuppression is main toxicity Challenge: integrate RIT into the care plan for the follicular patient to maximize DFS/OS