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Epidemiology of heme malignancies

Epidemiology of heme malignancies

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Epidemiology of heme malignancies

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  1. Epidemiology of heme malignancies Julie Kasperzyk, ScD January 11, 2012

  2. Background

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

  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. Global lymphoma incidence

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

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

  9. Heme cancer mortality rates in the US from 1975-2007

  10. www.lls.org

  11. Leukemia

  12. 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

  13. Number of new cases & deaths in US, 2010

  14. Rates of Acute Leukemia (ALL & AML) by age and sex, US ALL AML

  15. 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

  16. 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

  17. Rates of Chronic Leukemia (CLL & CML) by age and sex, US CLL CML

  18. 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

  19. 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

  20. 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 (egGleevec) which has dramatically improved survival http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CML.html

  21. Leukemia rates by race/ethnicity, US Source: SEER

  22. Atomic bomb survivors J RadiatRes (Tokyo). 1991 Dec;32 Suppl 2:54-63.

  23. 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

  24. Lymphoma

  25. 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)

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

  27. Number of new cases & deaths in US, 2010

  28. Rates of NHL & HL by age, US

  29. Rates of NHL & HL by age and sex,US

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

  31. 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

  32. 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

  33. 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.

  34. 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

  35. 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.

  36. 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%

  37. Multiple Myeloma

  38. 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

  39. Rates of MM by age and sex, US

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

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

  42. 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%