Non Hodgkin S Lymphoma
Table of Contents
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Epidemiology
- Male:Female —> 1.5:1
- Icrease with age
- Burkitt Lymphoma and Lymphoblastic Lymphoma —> more common in young age
- Both highly aggressive
- Burkitt Lymphoma and Lymphoblastic Lymphoma —> more common in young age
- white>black
- 5yr OS in black is 6% less
- Developed > developing
- highest in US, lowest in China
Etiology
- Pectiside
- Farmers
- Hair Dye
NHL Type | Viral Factor | Comment |
---|---|---|
Adult T-Cell Lymphoma/Leukemia | Human t-cell Lymphotropic Virus | Endemic Area(southern Japan-Caribbean) |
Burkitt's Lymphoma | HIV | Africa, higher risk for more aggressive lymphoma* |
Mucosa-Associated Lymphoma Tissue | Helicobacter Pylori | eradication of H-Pylori may be beneficial |
Classification
Know these types:( in order of frequency)
- Diffuse Large B Cell Lymphoma (30%)
- Follicular Lymphoma (20%)
- Small Lymphocytic Lymphoma/CLL (<10%)
- Mantle Cell Lymphoma
- Peripheral T-Cell Lymphoma
- Marginal Zone B-cell Lymphoma
Molecular Biology
Translocation | NHL Type | Gene Involved | Comment |
---|---|---|---|
t(14:18) | Follicular Lymphoma | bcl-2 | |
t(8:14) | Burkitt's Lymphoma | c-myc | |
t(11:14) | Mantle Cell Lymphoma | bcl-1 | encodes cyclin D1; function is cell cycle control: G1 progression |
t(11:18) | MALT | associated w poor response to antibiotic therapy in gastric MALT, found also in lung and eye | |
DLBCL | bcl-6 | in 1/3 of patients |
IPI for NHL
- Age>60
- LDH > 1xN
- ECOG 2-4
- >1 extranodal site
- Stage III-IV
Total IPI points | 5yr Survival |
---|---|
0-1 | 70% |
2 | 50% |
3 | 40% |
4-5 | 25% |
FLIPI
- Age>60
- Stage III-IV
- abN LDH
- >4 nodal areas
- Hgb<120
Other prognostic factors include
- Histo type —> DLCL, mantle, T-cell, NK cell
- Bulk —> >10 cm
- B symptoms
- High s-phase fraction
- Ki-67>80%
- HLA-DR expression
- beta2-microglobulin
- bcl-2 protein
- bcl-6 rearrangement
- CD44 expression
Common Lymphoma and the Role of Radiation
Low-Grade Lymphomas
Follicular Lymphoma
- A lymphoma of follicle center B cells (centrocytes and centroblasts), which has at least a partially follicular pattern.
- Morphology
- A mixture of centrocytes (cleaved follicle center cells) and centroblasts (large noncleaved follicle center cells)
- Follicular pattern
- Clinical aggressiveness of the tumor increases with increasing numbers of centroblasts
- GRADES
- 1: 0–5 centroblasts per high-power field
- 2: 6–15 centroblasts per high-power field
- 3: >15 centroblasts per high-power field
- 3a: >15 centroblasts, but centrocytes are still present
- 3b: Centroblasts form solid sheets with no residual centrocytes
- IMMUNOPHENOTYPE
- Surface immunoglobulin
- 60% —> IgG
- 40% —> IgG or, less often, IgA
- pan-B-cell–associated antigens
- Most are CD10+
- CD5−
- CD23−/+
- Most cases are bcl-2+
- Nuclear bcl-6 is expressed by at least some of the neoplastic cells
- Ki-67+ fraction is lower than that of reactive follicles
- Surface immunoglobulin
- GENETICS:
- t(14;18)(q32;q21)
- BCL-2 gene
- Abnormalities in 3q27
- BCL6 (40%)
- More risk for transformation to DLBCL
- BCL6 (40%)
Clinical Features
- The second most common lymphoma
- 30% of all NHLs
- Female>Male
- 1.7:1
- Predominantly involving lymph nodes
- But also:
- Spleen
- Bone marrow
- Occasionally:
- Peripheral blood
- Extranodal sites
- But also:
- Indolent
- Median survivals: ~10 years
- Not usually curable
- Transformation risk to diffuse and large cell: ~30% in 10yr
- DLBCL evloved from follicular is more resistant to treatment
- Median Survival after transformation: ~1.2yr
- DLBCL evloved from follicular is more resistant to treatment
Therapy of Localized Follicular Lymphoma
Stage I and II
- RT alone is standard treatment
- Stanford University —> Observation may provide same outcome!
- 10-year freedom from treatment failure —> 40-50%
- 10-year OS —> 40-80%
- Median survival —> 12-15 years
- Adding CHEMOTHERAPY —> no clear benefit
- Randomized studies (1970s)
- non–Adriamycin-containing chemo added to Rt —> no benefit
- M.D Anderson single arm study
- COP (cyclophosphamide, vincristine, and prednisone) or CHOP-B (cyclophosphamide, doxorubicin, vincristine, prednisone plus bleomycin)
- Better Freedom from Recurrence ( compared to historical data
- No OS benefit
- COP (cyclophosphamide, vincristine, and prednisone) or CHOP-B (cyclophosphamide, doxorubicin, vincristine, prednisone plus bleomycin)
- Randomized studies (1970s)
When to consider Chemo?
- Grade 3
- Stage II disease with multiple sites of involvement
- Bulky nodes
Adverse prognostic factors for freedom from treatment failure:
- Age
- Garde 3
- Extensive clinical stage IIA
- Bulky disease (defined as >2 or 3 cm)
- Extranodal presentations
Radiation Technique:
- Intent is curative
- High Energy Photon
- 6MV
- Preparation tests:
- Hematology Consult
- If young female patient —> R/O pregnancy
- If pelvic RT —> Oophoroplexy
- Baseline endocrinological
- Pulmunary Function test
- Renal Function Test
- CT Simulation
- Chest versus Abdo versus Neck
- Position:
- Supine
- Arms at sides if Neck or Abdo/Pelvis
- Arms up if chest
- Surface lead marker: any Enlarged LN
- Aides:
- knee cushion
- head rest
- Dose:
- 30Gy + boost 6Gy to GTV
- 3D Conventional
- GTV
- CTV is Involved Field Nodal Area
- PTV —> margin ( ~1cm )
- Organs at risk
- Dose Constraint
- Outcome
- Median Survival : 10yr
- 10yr Disease Free Survival: 50%
Advance Stage ( III and IV )
- 80% of cases
- Treatment primarily is systemiv therapy
- Chemotherapy +/- immunotherapy
- Chemo
- CHOP ( Cyclophosphamide, doxorubicin, vincristine, prednisone)
- Immunotherapy
- Rituximab
- anti-CD20 Ab
- Rituximab
- Chemo
- Chemotherapy +/- immunotherapy
- Low grade and non-symptomatic —> Observation is a choice as well
Role of Radiation in advance stage?
- NCI prospective randomized trial
- Chemo + RT versus no initial treatment
- 4yr DFS better in combined modality group (50% vs 12%)
- No OS benefit!
Marginal Zone Lymphomas
- Extranodal
- MALT ( mucosal associated Lymphoid Tissue ) Lymphoma
- Nodal
- =monocytoid B-cell lymphoma
- older age-group
- Morphology:
- Heterogeneous small B cells
- Marginal zone (centrocytelike) cells
- Monocytoid cells
- With plasma cell differentiation in 40% of the cases
- Infiltration of mucosa, lymphoepithelial lesions, clonal proliferation of centrocyte-like B-cells
- Immunophenotype:
- Surface Ig
- pan-B-antigen
- BUT CD5 - and CD10 -
Extranodal MZL
- Most commonly in stomach
- Salivary glands
- Waldeyer's ring
- Large and small intestine
- Thyroid
- Orbit & Conjunctivae
- Lung
- Breast
- Skin
Either epithelial mucosa or columnar epithelium
- Clinical course is indolent
- Usually present in early stage
- Usually limited to invloved organ
- Occasionally adjucant LN +
- Result of an antigenic simulation
- Hashimoto's Thyroiditis —> higher risk of MALT in thyroid
- Sogren's Syn
- H.pylori —> stomach
Treatment of MALT (Stomach)
- If H-Pylori +
- First step —. eradication of H-Pylori
- 50% of patients eventually will require further treatment
- 30-50% —> persistent disease
- 15% of CR will progress
- 50% of patients eventually will require further treatment
- First step —. eradication of H-Pylori
- If H-pylori - and in case of progression
- IFRT
- Rt to stomach and regional LN
- 30Gy/20fr ( 4 weeks )
- ~90% CR
- 4yr Freedom from treatment failure —> 90%
- 4yr OS —> 80%
- 4yr DSS —> 100%
- IFRT
page revision: 53, last edited: 30 Jun 2012 19:07