Post on 16-Dec-2015
EPIDEMIOLOGY OF HEME MALIGNANCIES
Julie Kasperzyk, ScD
January 11, 2012
Background
Roman & Smith Histopathology 2011, 58, 4–14.
Global Cancer Frequency
Definition: Hematological malignancies Group of cancers that affect the blood,
lymph nodes, and bone marrow Account for ~9% of new cancer
diagnoses in the US 3 major groups
Leukemia: starts in bone marrow and spreads to blood/periphery
Lymphoma: occurs in lymphoid tissue Plasma cell neoplasms (e.g. multiple
myeloma)
Overview of blood cells
All heme malignancies
(100%)Leukemi
a(~40%)
Acute Lymphocytic (ALL): most common childhood leukemia
Chronic Lymphocytic (CLL): most common leukemia in elderly
Acute Myeloid (AML)
Chronic Myeloid (CML): more common in adults, rare in children
Other leukemias
Lymphoma
(~50%)Non-Hodgkin lymphoma (NHL): many histological subtypes, more common than HL
Hodgkin lymphoma (HL): morphologically distinct Reed-Sternberg cells
Plasma Cell
Neoplasm(~10%)
Multiple myeloma (MM)
Other
Global lymphoma incidence
Multiple myeloma
Hodgkin lymphoma
Non-Hodgkin lymphoma
Leukemia
0 2 4 6 8 10 12 14
Northern AmericaLatin AmericaAsiaAfrica
Per 100,000
Age-standardized rates of heme cancers in selected regions
GLOBOCAN 2008, IARC
Surveillance, Epidemiology and End Results (SEER) Program. A source for US cancer statistics.
Heme cancer incidence rates in the US from 1975-2007
Heme cancer mortality rates in the US from 1975-2007
www.lls.org
Leukemia
Acute vs. chronic
Acute Elevated immature blood cells in the marrow and
blood Rapid progression and accumulation of malignant
cells Requires immediate treatment ALL is most common form of leukemia in children
Chronic Elevated mature (or relatively mature) blood cells Takes months to years to progress Sometimes treated conservatively (esp. low-grade) Mostly occurs at older ages
Number of new cases & deaths in US, 2010
ALL
AML
CLLCM
L
Other
/unc
lass
ified
02000400060008000
10000120001400016000
New CasesDeaths
Rates of Acute Leukemia (ALL & AML) by age and sex, US
ALL AML
ALL
Can involve B (~85%) or T (~15%) lymphocytes, rarely natural killer cells
Risk factors largely unknown Ionizing radiation Higher rates found in more developed
countries and families with higher SES 5-year survival
66% for all ages 91% for children under 5 yrs
www.lls.org
AML
Involves myeloid progenitor cells Potential risk factors:
Chronic benzene exposure (found in cigarette smoke)
Certain genetic disorders Down syndrome increased risk of AML
Past chemo or radiation therapy History of other blood cancers or disorders
5-year survival 24% for all ages 61% for children under 15 yrs
www.lls.org
Rates of Chronic Leukemia (CLL & CML) by age and sex, US
CLL CML
CLL
Most common type of leukemia in adults Begins in the bone marrow and can progress
either slowly or quickly depending on subtype 95% are B lymphocyte origin, with remaining
5% either T cell or natural killer cell origin Risk factors
Family history (1st degree relatives of CLL cases are 3-4x more likely to develop CLL than people without family Hx)
Vietnam veterans (agent orange exposure) 5-year survival: 80% for all ages
CML
Involves proliferation of mature and immature myeloid cells, accumulate in bone marrow and blood
Potential risk factors Ionizing radiation Radiation therapy from treatment of other
cancers 5-year survival: 55% for all ages
CML and the Philadelphia chromosome
Translocation between BCR and c-ABL
BCR-ABL acts as a tyrosine kinase, and constitutive expression increases rate of mitosis and decreases apoptosis
Treated with tyrosine kinase inhibitors (eg Gleevec) which has dramatically improved survival
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CML.html
Leukemia rates by race/ethnicity, US
Source: SEER
Atomic bomb survivors
J Radiat Res (Tokyo). 1991 Dec;32 Suppl 2:54-63.
Treatments for leukemia
Depends on subtype and risk factors Multi-drug chemotherapy regimen Less common: radiation therapy or bone
marrow transplant Consequence if untreated: disruption of
normal blood production Anemia: caused by low levels of RBC production Neutropenia: more susceptible to infections due
to low numbers of neutrophils (a type of WBC) Bleeding/bruising: caused by low platelet levels
Lymphoma
Non-Hodgkin (NHL) & Hodgkin (HL) Affect the lymphatic system NHL: Mostly (~85%) B-cell origin, and
remaining 15% T-cell or natural killer cell origin
HL: B-cell origin Major risk factors
Male gender Caucasian race Immunodeficiency syndromes (acquired
and inherited)
Lymphoma subtype frequencies
Roman & Smith Histopathology 2011, 58, 4–14.
Hodgkin lymphoma subtypes
Source: Haematological Malignancy Research Network, 2004-2009
New Cases Deaths0
10000
20000
30000
40000
50000
60000
70000
NHLHL
Number of new cases & deaths in US, 2010
Rates of NHL & HL by age, US
Rates of NHL & HL by age and sex, US
Rates over time of NHL & HL by race/ethnicity, US
NHL HL Source: SEER
Epstein-Barr Virus (EBV)
Herpesvirus family Infects nasopharyngeal epithelial cells
and B lymphocytes Promotes proliferation of infected cells
Ubiquitous in human populations worldwide Childhood infections are generally mild Adolescent/adult infection can lead to
mononucleosis
EBV & Burkitt lymphoma
Rare, aggressive NHL with B-cell origin Endemic in regions of Africa where Epstein-Barr
virus (EBV) and malaria are common Malaria causes T cell immunodeficiency
Occurs typically in young children, beginning in the lymph nodes in the neck
Nearly 100% of tumors from African Burkitt’s lymphoma carry the EBV genome and express EBV-encoded antigens
Other types (weakly linked to EBV): sporadic (non-African) immunodeficiency-associated
EBV & HL
~1/3 of tumors positive for EBV in developed countries
2- to 3- fold increased HL risk with history of infectious mononucleosis
Hygiene hypothesis Lower risk with daycare, higher birth order,
larger sibship size
Mueller & Grufferman. Hodgkin Lymphoma in Cancer Epidemiology and Prevention. 3rd edition.
HTLV-1 & adult T-cell leukemia/lymphoma (ATLL)
Human T-lymphotropic virus type 1 (HTLV-1) Endemic to Japan, Caribbean, & parts of
Central Africa Immortalizes infected T-cells (similar to
HIV) HTLV-1 is a necessary but not sufficient
cause of ATLL ~3% of infected individuals develop ATLL
HIV & lymphoma
HIV weakens the immune system
More susceptible to other infectious agents (e.g. EBV) that increase lymphoma risk
Introduction of antiretroviral therapy has reduced incidence of NHL among HIV-infected individuals
Engels et al. Int J Cancer. 2008;123:187-94.
Treatment for lymphoma
Primarily chemotherapy and radiation therapy In some cases: bone marrow transplant or
immunotherapy 5-year survival rate in US
NHL 1960-1963 (Caucasians only): 31% 1999-2006 (all races): 69%
HL 1960-1963 (Caucasians only): 40% 1999-2006 (all races): 88% Persons <20 yrs old: 96%
Multiple Myeloma
MM
Cancer of plasma cells (mature B lymphocytes), amass primarily in the bone marrow
Risk factors Male gender African American race/ethnicity History of MGUS (monoclonal gammopathy of
unknown significance) Environmental exposures (Agent Orange,
smoking, radiation, pesticides) Obesity
www.lls.org
Rates of MM by age and sex, US
Rates over time of MM by race/ethnicity, US
Source: SEER
Obesity & MM
RR for obesity vs. normal weight
Overall: RR=1.21
Wallin & Larssen. European Journal Of Cancer 2011;47:1606-15.
Treatment for multiple myeloma Drug therapy (including chemotherapy),
stem cell transplantation, radiation therapy
5-year survival 1960-1963 (Caucasians only): 12% 1999-2006 (all races): 39%