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EPIDEMIOLOGY OF HEME MALIGNANCIES Julie Kasperzyk, ScD January 11, 2012.

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Presentation on theme: "EPIDEMIOLOGY OF HEME MALIGNANCIES Julie Kasperzyk, ScD January 11, 2012."— Presentation transcript:

1 EPIDEMIOLOGY OF HEME MALIGNANCIES Julie Kasperzyk, ScD January 11, 2012

2 Background

3 Roman & Smith Histopathology 2011, 58, 4–14. Global Cancer Frequency

4 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)

5 Overview of blood cells

6 All heme malignancies (100%) Leukemia (~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

7 Global lymphoma incidence

8 Age-standardized rates of heme cancers in selected regions GLOBOCAN 2008, IARC

9 Surveillance, Epidemiology and End Results (SEER) Program. A source for US cancer statistics. Heme cancer incidence rates in the US from 1975-2007

10 Heme cancer mortality rates in the US from 1975-2007


12 Leukemia

13 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

14 Number of new cases & deaths in US, 2010

15 Rates of Acute Leukemia (ALL & AML) by age and sex, US ALLAML

16 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

17 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

18 Rates of Chronic Leukemia (CLL & CML) by age and sex, US CLLCML

19 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 (1 st 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

20 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

21 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 Pages/C/CML.html

22 Leukemia rates by race/ethnicity, US Source: SEER

23 Atomic bomb survivors J Radiat Res (Tokyo).J Radiat Res (Tokyo). 1991 Dec;32 Suppl 2:54-63.

24 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

25 Lymphoma

26 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)

27 Lymphoma subtype frequencies Roman & Smith Histopathology 2011, 58, 4–14. Hodgkin lymphoma subtypes Source: Haematological Malignancy Research Network, 2004-2009

28 Number of new cases & deaths in US, 2010

29 Rates of NHL & HL by age, US

30 Rates of NHL & HL by age and sex, US

31 Rates over time of NHL & HL by race/ethnicity, US NHLHL Source: SEER

32 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

33 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

34 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. 3 rd edition.

35 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

36 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.

37 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%

38 Multiple Myeloma

39 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

40 Rates of MM by age and sex, US

41 Rates over time of MM by race/ethnicity, US Source: SEER

42 Obesity & MM  RR for obesity vs. normal weight  Overall: RR=1.21 Wallin & Larssen. European Journal Of Cancer 2011;47:1606-15.

43 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%

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