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%