Non-Hodgkins Lymphoma (NHL)

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Non-Hodgkins Lymphoma (NHL)

• Hazim Ogorban, Sharon Welburn, Lingshu Xue

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Table of Contents

• Overview of NHL
• Description of NHL
• Incidence/Prevalence of NHL
• Mortality
• Etiology of NHL
• Physiologic Characteristics
• Genetic Characteristics
• Etiologic Model
• Risk and Treatment
• Risk Factors
• Detection
• Treatment Methods

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Overview of Non-Hodgkins Lymphoma
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What is Non-Hodgkins Lymphoma (NHL)?

• Cancer of lymphocytes (white blood cells)
• 5th Most common cancer in the U.S.
• Most common hematological malignancy (blood
  cancer) in developed countries
• Types of non-hodgkins
• Aggressive (fast-growing) vs. Indolent
  (slow-growing)
• B-cells (85 of all NHL) vs. T-cells
• Estimated new cases deaths in US in 2013
• 69,740 new cases
• 19,020 deaths

Actor Andy Whitfield who died 18 months after
diagnosis of Stage 4 NHL
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Types of NHL

• Over 40 different kinds of NHL
• Diffuse large B cell
• Most common type of high grade NHL (1/3 with NHL
  are this type)

T-cell Lymphomas
Peripheral T-cell Lymphoma
Skin (Cutaneous) Lymphoma (Mycosis Fungoides Sezary Syndrome)
Anaplastic Large Cell Lymphoma
Lymphoblastic Lymphoma (mainly T-cell but can be B-cell)
B-Cell Lymphomas
Diffuse Large B-cell Lymphoma
Follicular Lymphoma
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Tissue (MALT)
Mantle Cell Lymphoma
Burkitt Lymphoma
Mediastinal Large B-cell Lymphoma
Nodal Marginal Zone Lymphoma
Small Lymphocytic Lymphoma (SLL)
Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinaemia)
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World NHL incidence mortality

• Estimated age-standardized incidence and
  mortality rates men

• Estimated age-standardized incidence and
  mortality rates both sexes

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• US age-adjusted (2000 standard) NHL
  Incidence by gender, 1973-2010

Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Incidence - SEER 9 Regs Research Data,
Nov 2012 Sub (1973-2010) ltKatrina/Rita Population
Adjustmentgt - Linked To County Attributes - Total
U.S., 1969-2011 Counties, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013,
based on the November 2012 submission.
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US age-adjusted (2000 standard) NHL Incidence,
men, by race 1973-2010
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Incidence - SEER 9 Regs Research Data,
Nov 2012 Sub (1973-2010) ltKatrina/Rita Population
Adjustmentgt - Linked To County Attributes - Total
U.S., 1969-2011 Counties, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013,
based on the November 2012 submission.
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US age-adjusted (2000 standard) NHL Incidence by
age at diagnosis, 1973-2010
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Incidence - SEER 9 Regs Research Data,
Nov 2012 Sub (1973-2010) ltKatrina/Rita Population
Adjustmentgt - Linked To County Attributes - Total
U.S., 1969-2011 Counties, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013,
based on the November 2012 submission
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Israel 16.57 USA 13.73 Canada
13.20 Maldives 0.45
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Israel 18.48 USA 16.27 Canada15.20 Bahamas
0.78
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(No Transcript)
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Lebanon 7.29 Egypt 7.11 Equatorial Guinea
6.84
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http//statecancerprofiles.cancer.gov/cgi-bin/quic
kprofiles/profile.pl?00086
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http//statecancerpr
ofiles.cancer.gov/cgi-bin/quickprofiles/profile.pl
?00086
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Allegheny
http//statecancerprofiles
.cancer.gov/cgi-bin/quickprofiles/profile.pl?4208
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Allegheny
http//statecancerprofiles.canc
er.gov/cgi-bin/quickprofiles/profile.pl?42086
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U.S. age-adjusted (2000 standard) non-Hodgkin
lymphoma mortality, all ages, by gender
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
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U.S. age-adjusted (2000 standard) non-Hodgkin
lymphoma mortality, by age group
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
20
U.S. age-adjusted (2000 standard) non-Hodgkin
lymphoma mortality by race
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
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Mortality Estimates for 2013

• American Cancer Society estimates for 2013
• 69,740 will be diagnosed with NHL
• 37,600 male / 32,140 female
• 19,020 will die from this cancer
• 10,590 male / 8,430 female

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Annual Percentage Change (APC) in US

• Incidence

Estimated APC by age group Estimated APC by age group Estimated APC by age group Estimated APC by age group
Age group 20-49 50-64 65
1973-2010 1.2 1.4 2.0
Estimated APC (all races, all ages both genders) Estimated APC (all races, all ages both genders)
1975-1991 3.6
1991-2010 0.5
Estimated APC by race Estimated APC by race Estimated APC by race Estimated APC by race
  White Black other
1973-2010 1.8 2.2 1.3
Estimated APC by gender Estimated APC by gender Estimated APC by gender
  Male Female
1973-2010 1.8 1.6
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Incidence - SEER 9 Regs Research Data,
Nov 2012 Sub (1973-2010) ltKatrina/Rita Population
Adjustmentgt - Linked To County Attributes - Total
U.S., 1969-2011 Counties, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013,
based on the November 2012 submission
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US NHL Incidence, all ages
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US NHL Incidence by gender
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Annual Percentage Change (APC) in US
Mortality
Estimated APC (all races, all ages both genders) Estimated APC (all races, all ages both genders)
1975-1991 2.5
1991-1997 1.5
1997-2006 -3.1
2006-2010 -2.3
Estimated APC by age group Estimated APC by age group Estimated APC by age group Estimated APC by age group
Age group 20-49 50-64 65
1969-2010 -1.1 -0.6 1.2
Estimated APC by race Estimated APC by race Estimated APC by race Estimated APC by race
  White Black Other
1973-2010 0.6 0.8 0.4
Estimated APC by gender Estimated APC by gender Estimated APC by gender
  Male Female
1969-2010 0.7 0.4
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
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White .M 1969-1997 APC
2.06 1997-2010 APC - 2.74
Black .M 1969-1996 APC 2.23
1996-2010 APC - 2.44
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
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Male 1969-1997 APC
2.05 1997-2010 APC - 2.76
Female 1969-1997 APC
1.88 1997-2010 APC - 3.27
Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Mortality - All COD, Aggregated With
State, Total U.S. (1969-2010) ltKatrina/Rita
Population Adjustmentgt, National Cancer
Institute, DCCPS, Surveillance Research Program,
Surveillance Systems Branch, released April 2013.
Underlying mortality data provided by NCHS
(www.cdc.gov/nchs).
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US statistics according to the WHO classification
of tumors of hematopoietic and lymphoid tissues
(2008)
Lymphoma Subtype Recode ICD-O-3/WHO 2008 Percentage
2(a)2.3.1 DLBCL, NOS 59,473 34.4
2(a)2.6 Follicular lymphoma 32,402 18.7
2(a)2.1.1 Chronic/Small lymphocytic leuk/lymph 11,327 6.5
2(a)3 Non-Hodgkin lymphoma, B-cell, NOS 10,944 6.3
4 Lymphoid neoplasm, NOS 10,007 5.7
2(a)2.5.2 Extranodal MZL, MALT type 9,763 5.6
2(a)2.1.3 Mantle-cell lymphoma 6,429 3.7
2(a)2.5.3 Nodal MZL 4,969 2.8
2(b)2.1.1 Mycosis fungoides 4,076 2.3
2(b)2.2.1 Peripheral T-cell lymphoma, NOS 3,496 2
2(a)2.4 Burkitt lymphoma/leukemia 3,329 1.9

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NHL 5 year relative survival, 50 years old men
by stage and year at diagnosis
Year of diagnosis Localized Localized Regional Regional Distant Distant Unstaged Unstaged
Year of diagnosis N Survival N Survival N Survival N Survival
1996-2002 5,285 75 2,599 60.2 8,979 47.9 1,760 57.4
2003-2009 9,688 79 5,320 67.9 19,329 57.7 3,029 64

Surveillance, Epidemiology, and End Results
(SEER) Program (www.seer.cancer.gov) SEERStat
Database Incidence - SEER 18 Regs Research Data
Hurricane Katrina Impacted Louisiana Cases, Nov
2012 Sub (1973-2010 varying) - Linked To County
Attributes - Total U.S., 1969-2011 Counties,
National Cancer Institute, DCCPS, Surveillance
Research Program, Surveillance Systems Branch,
released April 2013, based on the November 2012
submission.
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Etiology of NHL
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Map of Lymph Nodes
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Physiologic Characteristics

• Signs and symptoms
• Dependent on where in the body it is
• Most common
• Enlarged lymph nodes
• Swollen abdomen (belly)
• Feeling full after only a small amount of food
• Chest pain or pressure
• Shortness of breath or cough
• Fever
• Weight loss
• Night sweats
• Fatigue (extreme tiredness)

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Physiologic Characteristics

• How does it spread?
• Lymph tissue is found throughout the body, so NHL
  can begin almost everywhere and through the
  lymphatic system spread to many other organs and
  tissues

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Normal Lymph System
Shown lymph vessels and lymph organs (lymph
nodes, tonsils, thymus, spleen, and bone
marrow). Notice the lymph (clear) fluid.
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Stage 1 Adult NHL
Cancer is found in one lymphatic area. Note
Shown Stage 1E Cancer is found in one organ or
area outside lymph nodes
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Stage 2 Adult NHL
Cancer found in 2 or more lymph node groups, and
both are either above (a) or below (b) the
diaphragm. Not Shown Stage IIE is when cancer
is found outside the lymph node as well in an
organ or area on the same side of the diaphragm
as the lymph nodes with cancer.
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Stage 3 Adult NHL
Cancer is found in one or more lymph node groups
above and below diaphragm (a). Stage IIIE,
cancer is found in lymph node groups above and
below diaphragm and outside in nearby organ or
area (b). Stage IIIS, cancer is found in lymph
node groups above and below diaphragm (a) and in
spleen (c). Stage III plus S, cancer found in
lymph nodes above and below diaphragm, outside in
nearby organ/areas (b), and in spleen (c).
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Stage 4 Adult NHL
Cancer found throughout one or more organs not
part of lymphatic area (a) or in one organ that
isnt part of lymphatic area and has spread to
lymph nodes far away from that organ (b) or
cerebrospinal fluid, liver, bone marrow, or lungs.
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Genetic Characteristics

• Unlike most cancers, DNA changes related to NHL
  are usually acquired after birth, not inherited
• Translocations DNA from one chromosome breaks
  off and attaches to a different chromosome
• most common DNA change to cause NHL
• Can cause oncogenes to turn on or tumor
  suppressor genes to turnoff
• Normal tissue
• Malignant tissue

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Etiologic Model
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Risk factors
There is no definite risk factors
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Risk factors

• Age and gender
• Weakened immune system
• Infections
• Coeliac disease
• Family history of NHL
• Previous cancer and treatment

• Chemicals at work
• Hair dye
• Recreational drugs
• Sunlight
• Obesity/diabetes
• Medicines
• Hormones

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Weakened immune system

• People whose immune system is not working as well
  as it should are more likely to develop a
  lymphoma. Immunity can be lowered for the
  following reasons
• Transplant
• HIV or AIDS
• Autoimmune diseases(coeliac disease, SLE,
  rheumatoid arthritis and , Sjogren's syndrome )

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Infections

•  Human T cell lymphoma virus 1 (HTLV1) 
•  Epstein Barr virus
• - Burkitt's lymphoma
•  Helicobacter pylori
• -MALT lymphoma
• (mucosa associated lymphoid
  tissue)

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EBV associated NHL

• Immunodeficient Patients
• AIDS-related lymphoma
• Post-transplant lymphoproliferative disease (LPD)

• Immunocompetent Patients
• Burkitts lymphoma
• EBV infections ?
• Deregulation of c-myc gene on chromosome
  8?

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EBV associated NHL
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Occupational and environmental factors

• pesticide exposure
• evidence 1
• Use of synthetic organic pesticides
• evidence 2
• tumor initiating and/or promoting effects in
  animal
• epidemiology evidence
• No associations

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Chemical exposure

• benzene exposure
• Solvent exposure
• Nitrates exposure
• .
• 1.inconsistant results
• 2.multiple exposure
• 3. lack of exposure-response pattern

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Radiation exposure

• Nonionizing UV radiation from sunlight
• -- beneficial ?
• -- assessing lifetime of exposure
• --recall bias
• Diagnostic radiation exposure
• -- no association

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Family history of NHL

• Family history
• Genetic variation
• TNF, IL10, genes coding key cytokines
• Interactions with environment and lifestyle
  factors
• few study

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Lifestyle and personal factors

• Tobacco and alcohol use
• Dietary factors
• Hair dyes
• Weakness
• 1. lack of cohort study
• 2. lack of biological mechanism study
• 3. recall bias

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• Thanks
• Question?