powerpoint presentationwilliams/lympho… · ppt file · web view · 2005-10-31goals understand...
TRANSCRIPT
![Page 1: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/1.jpg)
Goals
• Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma– Clinically and biologically
• Understand the differences between aggressive NHL and indolent NHL– Clinically and biologically
![Page 2: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/2.jpg)
Definition of Lymphoma• Heterogeneous group of lymphoproliferative malignancies
– Results from clonal expansion of tumor cells derived from B, T, or NK cells
– 85%-90% in the US are derived from B cells
• Variable clinical presentations– Range from asymptomatic pick up on routine blood work to
painless adenopathy to an emergent medical problem• Pain, failure to thrive, organ failure
• Characterized by variable natural histories and therapeutic responses
C
![Page 3: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/3.jpg)
0
20
40
60
80
100
120
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
NHL
Hodgkin’s
~56,390 NHL cases/y~7,350 HD cases/y
Age at Diagnosis for Hodgkin’s andNon-Hodgkin’s Lymphoma
Data for diagnoses from 1997 to 2001.At: http://seer.cancer.gov. Accessed March 23, 2005.
Age at diagnosis (y)
Cas
es/1
00,0
00
![Page 4: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/4.jpg)
Adapted from Greenlee et al. CA Cancer J Clin. 2001;51:15. Adapted from Jemal et al. CA Cancer J Clin. 2005;55:10.
United States
0
15,000
30,000
45,000
60,000
1980 1985 1990 1995 2000 2005
Estim
ated
ann
ual i
ncid
ence
Year
~4% compound annual increase in incidence
Non-Hodgkin’s Lymphoma:Epidemiology
![Page 5: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/5.jpg)
Hodgkin’s Disease
![Page 6: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/6.jpg)
Hodgkin Biology• RS is a “crippled” germinal center B cell
– does not have normal B cell surface antigens– micromanipulation of single RS followed by PCR demonstrates
clonally rearranged, but non functional immunoglobulin genes• somatic mutations result in stop codon (no sIg)• no apoptotic death malignant transformation
– unclear how this occurs; ? EBV– unclear how cells end up with RS phenotype
![Page 7: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/7.jpg)
Hodgkin’s Disease
• Clinical features– Often seen in young adults– Wide variety of presentations
• B symptoms (fevers, night sweats, wt loss)• Pruritis• Cough/SOB• Pain• Painless adenopathy
![Page 8: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/8.jpg)
Hodgkin’s Disease
• Approach to the Patient– staging evaluation
• H & P• CBC, diff, plts• ESR, LDH, albumin, LFT’s, Cr• CT scans chest/abd/pelvis• bone marrow evaluation• PET scan in selected cases
![Page 9: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/9.jpg)
Ann Arbor Staging System for Hodgkin's Disease and Non-Hodgkin's Lymphoma
Stage I Stage II Stage III Stage IV
Reprinted with permission. Adapted from Skarin. Dana-Farber Cancer Institute Atlas
of Diagnostic Oncology. 1991.
![Page 10: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/10.jpg)
Hodgkin’s Disease
• Typical staging results– Most often disease is localized to above the diaphragm– Common to have extensive mediastinal disease
• Tends to spread to contiguous nodal groups– Unlike NHL
![Page 11: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/11.jpg)
Approach to the Patient
• Hodgkin’s Disease– approach dictated mainly by where the disease is
located rather (results of staging) than the exact histologic subtype
• NHL– approach is often dictated more by the histologic
subtype than the results of staging
![Page 12: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/12.jpg)
Hodgkin Lymphoma: Treatment of limited stage disease
![Page 13: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/13.jpg)
Hodgkin Lymphoma: Prognostic Factors
![Page 14: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/14.jpg)
Hodgkins Disease Summary
• B cell lymphoma- several histologic subtypes
- Generally does not affect the approach to the patient– Reed-Sternberg Cells
• Tends to occur in young adults• Mediastinal disease common• Spreads to contiguous nodes• Common to have a “localized” presentation• Highly curable with current treatments
![Page 15: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/15.jpg)
Non-Hodgkin’s Lymphoma• 30ish histologic subtypes
– B cell (85%), T cell, NK cell– Histologic subtype dictates the approach to the patient
• Median age at diagnosis 60• Often widespread disease at diagnosis• Wide variation in outcome
– Some cases rapidly fatal– Some cases readily curable– Some cases incurable but patient can live for many years with
good quality of life
![Page 16: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/16.jpg)
WHO Classification:B-Cell Malignancies
Harris NL et al. J Clin Oncol. 1999;17:3835-3849.
Precursor B-cell neoplasm• Precursor B-lymphoblastic leukemia/lymphoma
Mature (peripheral) B-cell neoplasms• B-cell chronic lymphocytic leukemia/
small lymphocytic lymphoma • B-cell prolymphocytic leukemia • Lymphoplasmacytic lymphoma • Splenic marginal-zone B-cell lymphoma • Nodal marginal-zone lymphoma • Extranodal marginal-zone B-cell
lymphoma, mucosa-associated lymphoid tissue (MALT) type
• Hairy cell leukemia • Plasma-cell myeloma/
plasmacytoma • Follicular lymphoma • Mantle-cell lymphoma • Diffuse large B-cell lymphoma
(DLBCL) • Burkitt's lymphoma/Burkitt's cell
leukemia• Blastic NK-cell leukemia
![Page 17: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/17.jpg)
WHO Classification:T-Cell MalignanciesPrecursor T-cell neoplasm• Precursor T-lymphoblastic leukemia/lymphoma
Mature (peripheral) T-cell neoplasms• T-cell prolymphocytic leukemia • T-cell granular lymphocytic leukemia • Aggressive NK-cell leukemia • Adult T-cell lymphoma/leukemia (HTLV1+) • Extranodal NK/T-cell lymphoma, nasal
type• Enteropathy-type T-cell lymphoma • Hepatosplenic gamma-delta T-cell
lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Mycosis fungoides/Sézary syndrome • Primary cutaneous anaplastic large cell
lymphoma, T/null cell • Peripheral T-cell lymphoma, unspecified • Angioimmunoblastic T-cell lymphoma • Primary systemic anaplastic large cell
lymphoma, T/null cell• Blastic NK lymphoma
Harris NL et al. J Clin Oncol. 1999;17:3835-3849.
![Page 18: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/18.jpg)
B-Cell Development
MUM1
HLA-DR CD34
Stem cell
Pre-pre–B cell
Pre–B cell
Immature B cell
Mature B cell
HLA-DR CD19
HLA-DR CD19
HLA-DR
CD19CD20CD21
CD22CD79as-IgM
CD20
CD10
CD79a
s-IgM & IgD
CD19CD20
CD21CD22
HLA-DR
s-IgM/G/A
s-IgM/G/A
CD79a
CD19CD20CD21
CD22
HLA-DR
CD10
CD19CD20CD138±
CD22
HLA-DR
CD79a
CD79a CD138PCA-1
Follicle-center B cell
Immunoblast
Plasma cell
Precursor cellsVirgin (naïve) B cellsGerminal-center and post–germinal-center B cells
MUM1
TdT
TdTc-CD22c-CD79a
TdTc-CD22c-CD79a
c-
bcl6
c-Ig
c-Ig
![Page 19: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/19.jpg)
Antigen Expression in B-Cell Lineage
Pre-B Early B Mature B Plasmacytoid B
Type of B cell lymphoma is a function of:
1) Where the cell was in development/maturation when it went “bad”
2) What molecular derangement occurred
PlasmaActivated BStem cell
Burkitts, FL, DLBCL WM MMMCL, CLLALL
Germinal center
Jaffe. In: Non-Hodgkin’s Lymphoma. 1997:84.
![Page 20: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/20.jpg)
Models of Chromosomal Translocations in NHL
REG = regulatory sequence.Harris NL et al. Hematology (Am Soc Hematol Educ Program). 2001:194-220.
Proto-oncogene
Proto-oncogene
TRANSCRIPTIONALDEREGULATION
FUSIONPROTEIN
TRANSLOCATION TRANSLOCATION
REG
REG REG
REG
REG REGCODING CODING
COD
CODING CODING
CODING ING
![Page 21: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/21.jpg)
Chromosomal Translocations Commonly Associated With Activation in B-Cell Malignancies
National Comprehensive Cancer Network. Practice Guidelines in Oncology. v.1.2005.
Oncogene Protein Translocation Disease
bcl-1 Cyclin D1 t(11;14) MCL
bcl-2 BCL2 (antiapoptosis) t(14;18) FL
myc Transcription factor t(8;14) Burkitt’s NHL
bcl-6 Zinc-finger transcription factor t(3;14) DLBCL (some
follicular NHL)
![Page 22: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/22.jpg)
Lymphoma Biology• Aggressive NHL
– short natural history (patients die within months if untreated)
– disease of rapid cellular proliferation– Potentially curable with chemotherapy
• Indolent NHL– long natural history (patients can live for many years
untreated)– disease of slow cellular accumulation– Generally incurable with chemotherapy
![Page 23: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/23.jpg)
NHL: Presentation and Staging
• Aggressive NHL– Patients likely to present with symptoms
• Indolent NHL– Patients likely to present with painless adenopathy
• Initial workup similar to Hodgkin Lymphoma
![Page 24: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/24.jpg)
NHL: Approach to the Patient
• Approach dictated mainly by histology– reliable hematopathology crucial
• Aggressive NHL– Cure is often the goal
• Indolent NHL– Cure is rarely the goal– Control is the goal
![Page 25: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/25.jpg)
Most Common NHLsCategory Frequency (%)Diffuse large B-cell 31
Follicular 22
Marginal-zone B-cell, MALT 8
Peripheral T-cell 7
Small B-lymphocytic/CLL 7
Mantle-cell lymphoma 6
Primary mediastinal large B-cell 2
Anaplastic large T/null cell 2
High-grade B-cell, Burkitt-like 2
Marginal-zone B-cell, nodal 2Precursor T-lymphoblastic lymphoma 2
Armitage JO, Weisenburger DD. J Clin Oncol. 1998;16:2780-2795.
![Page 26: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/26.jpg)
Follicular Lymphoma
![Page 27: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/27.jpg)
Approach to Indolent NHL• Indolent NHL: guiding treatment principle
• immediate treatment does not prolong overall survival for many patients
– When to treat?• constitutional symptoms• compromise of a vital organ by compression or infiltration, particularly
the bone marrow• bulky adenopathy• rapid progression• evidence of transformation
• Will often begin with relatively non-toxic treatments and escalate the intensity of the therapy
![Page 28: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/28.jpg)
![Page 29: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/29.jpg)
Diffuse Large B Cell Lymphoma
![Page 30: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/30.jpg)
Approach to Aggressive NHL
• Patients have the potential to be cured– Administer most effective therapy (no matter how
harsh) at diagnosis– If not cured, patients typically die within a few years of
diagnosis
![Page 31: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/31.jpg)
![Page 32: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/32.jpg)
International Prognostic Index for Age-Adjusted
Factor AdversePS ≥2LDH >NormalStage III-IV
Risk Group
Number of Factors Present
5-year DFSAge≤60
(%)
5-year OS Age≤60
(%)Low 0 86 83
Low-Intermediate 1 66 69
High-Intermediate 2 53 46
High 3 58 32
The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987-994.
![Page 33: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/33.jpg)
DLBCL: Subtypes Revealed by Expression Array
Prob
abili
ty
Overall survival (years)0 2 4 6 8 10
Germinal-centerB-cell–like
ActivatedB-cell–like
P = 7.9 E-6
1.00.8
0.60.40.20.0
Alizadeh AA et al. Nature. 2000;403:503-511.
Single histology with multiple molecular
subtypes
…with different outcomes
![Page 34: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/34.jpg)
Summary• NHL incidence increasing • Hodgkin incidence stable or decreasing• Hodgkin Lymphoma
– Characterized by the Reed-Sternberg Cells– Stage more important that histologic subtype– Often limited stage (stage I or II)– Spreads to contiguous nodes– Often affects younger patients– Very responsive to therapy– Cure rate quite high
![Page 35: PowerPoint Presentationwilliams/lympho… · PPT file · Web view · 2005-10-31Goals Understand the differences between Hodgkin Lymphoma and non-Hodgkin Lymphoma Clinically and](https://reader036.vdocuments.us/reader036/viewer/2022070608/5ab11c647f8b9aea528bfb50/html5/thumbnails/35.jpg)
Summary• NHL cure rate mediocre
– Many histologic subtypes• Often more important that the stage
– indolent vs. aggressive• Function of underlying biology
– indolent: • Often asymptomatic• Treatment: Less is more
– aggressive: • Often symptomatic• require aggressive treatment ASAP to achieve cure