1. Lymphoma- All you Need to know in ONE hour Cathleen Cook Pediatric Hematology/ Oncology March 12, 2014

2. Ranking of pediatric malignancies for children aged 0-14 years http://www.meb.uni-bonn.de/cancer.gov/CDR0000062872.html Leukemia Brain tumors Lymphoma

3. Ranking of pediatric malignancies for children aged 15-19 years http://www.meb.uni-bonn.de/cancer.gov/CDR0000062872.html Carcinomas and Melanoma Brain tumors Lymphoma

4. Hodgkin Lymphoma Non-Hodgkin Lymphoma Late Effects Juan PabloNicole Objectives

5. Epidemiology of Hodgkin Lymphoma O 5% of cancers ≤14 years of age O 15% of cancers ≥14 years of age O Bimodal age distribution

6. Associations with Hodgkin Lymphoma

7. What is Hodgkin Lymphoma? O Cancer of the lymphoreticular system

8. Hodgkin Lymphoma Explained http://www.youtube.com/watch?v=saYsSIsBObw&list=PLlacjr_GktwC9JDvcxvgGKQ4jMq2JAE0L

9. Reed-Sternberg (RS) Cells = Hallmark of classical Hodgkin Lymphoma

10. Other Subtypes of Hodgkin Lymphoma

11. To where can Hodgkin Lymphoma metastasize? Spleen Liver Bone Marrow Bone Brain

12. Symptoms of Hodgkin Lymphoma O Painless, nontender, firm, rubbery lymph node O Cough O Weight loss O Fever O Night sweats O Pruritus (itching) O Anorexia (appetite loss) O Tiredness/ Lethargy O Pain WORSENING with Alcohol B symptoms

13. 1:30 sec. --- 5:00 Nicole’s Symptoms http://www.youtube.com/watch?v=vsSrdEYjcpc

14. So how do we diagnose Nicole? Physical Exam

15. So how do we diagnose Nicole? Sites of Disease Source: Metzger M. Hodgkin Lymphoma Lecture. 2009

16. So how do we diagnose Nicole? Labs CBC with differential CMP LDH Uric Acid ESR CRP Ferritin EBV titers CMV titers

17. Diagnostic Work Up: Chest X-ray

18. Diagnostic Work Up: CT CAP

19. Diagnostic Work Up: PET Scan

20. Diagnostic Work Up: Bilateral Bone Marrow Biopsy/Aspirate http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Hodgkin-Lymphoma.aspx#Cancer_Summary

21. Diagnostic Work Up: Excisional Lymph Node Biopsy http://www.flickr.com/photos/santoshpath/5453069538/ http://tessascancerjourney2.blogspot.com/2010/11/lymph-node-biopsy.html

22. Summary of Nicole’s diagnostic work up for Hodgkin Lymphoma? Physical Exam CBC CMP LDH Uric Acid ESR CRP Ferritin EBV titers CMV titers Chest Xray- PA/L CT scan (CAP) PET scan Bone marrow aspirate/biopsy Excisional LN biopsy

23. So how do we stage Hodgkin Lymphoma? A= no “B symptoms B= fever (>38C), unexplained weight loss (>10%), drenching night sweats E= extranodal extension S= splenic involvement Source: Metzger M. Hodgkin Lymphoma Lecture. 2009

24. So how do we treat Hodgkin Lymphoma? O Prednisone (P) O Vinblastine (V) O Bleomycin (B) O Doxorubicin (A) O Vincristine (O) O Procarbizine (P) O Etoposide (E) O Cyclophosphamide (C)

25. So how do we treat Hodgkin Lymphoma? Source: Metzger M. Hodgkin Lymphoma Lecture. 2009

26. Hodgkin Lymphoma Non-Hodgkin Lymphoma Late Effects Juan PabloNicole Objectives

27. Epidemiology of Non-Hodgkin Lymphoma (NHL) O 60% of all lymphomas in children and adolescents O 8-10% of cancers between 5-19 yo O >70% have advance disease at diagnosis Source: Kliegman R, Staton B, et al. Nelson Textbook of Pediatrics Ebook. 19 th edition. 2011. pg 8002.

28. Associations with Non-Hodgkin Lymphoma Source: Kliegman R, Staton B, et al. Nelson Textbook of Pediatrics Ebook. 19 th edition. 2011. pg 8002.

29. What is Non-Hodgkin Lymphoma? O Cancer of the lymphocytes

30. Non-Hodgkin Lymphoma Explained https://www.youtube.com/watch?v=x3c9dy3MPZo

31. Subtypes of Non-Hodgkin Lymphoma 38% Burkitt lymphoma (BL) 29% Lymphoblastic lymphoma (LL) 20% Diffuse large B-cell lymphoma (DLBCL) 10% Anaplastic large cell lymphoma (ALCL) 0-14 years Source: Kliegman R, Staton B, et al. Nelson Textbook of Pediatrics Ebook. 19 th edition. 2011. pg 8003.

32. Subtypes of Non-Hodgkin Lymphoma 37% Diffuse large B-cell lymphoma (DLBCL) 21% Burkitt lymphoma (BL) 19% Lymphoblastic lymphoma (LL) 17% Anaplastic large cell lymphoma (ALCL) 15-19 years Source: Kliegman R, Staton B, et al. Nelson Textbook of Pediatrics Ebook. 19 th edition. 2011. pg 8003.

33. Clinical Presentation of Non-Hodgkin Lymphoma Jaw swelling Abdominal masses Orbital swelling Chest masses Paraspinal masses

34. Clinical Presentation of Non-Hodgkin Lymphoma

35. http://www.youtube.com/watch?v=Zx9SjYTr7CU Juan Pablo’s Symptoms Initial 1:00min

36. Non-Hodgkin Lymphoma- Tumor Lysis Syndrome Tumor masses (similar to leukocytosis with leukemia) http://www.nejm.org.ezproxy.etsu.edu:2048/doi/pdf/10.1056/NEJMra0904569

37. Tumor Lysis Syndrome http://www.nejm.org.ezproxy.etsu.edu:2048/doi/pdf/10.1056/NEJMra0904569 Uric Acid Phosphate Potassium Calcium Sodium NO CHANGE

38. Tumor Lysis Syndrome http://www.nejm.org.ezproxy.etsu.edu:2048/doi/pdf/10.1056/NEJMra0904569 http://www.nytimes.com/health/guides/disease/acute-gouty-arthritis/print.html Uric Acid Phosphate Potassium RISK OF Acute Kidney Injury -stones -renal failure

39. Tumor Lysis Syndrome http://www.nejm.org.ezproxy.etsu.edu:2048/doi/pdf/10.1056/NEJMra0904569 http://www.pinterest.com/pin/90986854945562677/ http://www.aaemrsa.org/communication/modernresident/2012/images/hands-lg.jpg Calcium RISK OF Chvostek sign Trousseau's sign

40. Emergency Presentations of Non-Hodgkin Lymphoma

41. So how do we diagnose Juan Pablo? Physical Exam

42. So how do we diagnose Juan Pablo? Labs CBC with differential CMP LDH Uric Acid ESR CRP Ferritin EBV titers CMV titers

43. Diagnostic Work Up: Chest X-ray

44. Diagnostic Work Up: CT CAP http://tmcr.usuhs.edu/tmcr/chapter8/differential3.htm http://www.radiologyschools.com/Radiology-Courses/gu/kidneys/lymphoma.html

45. Diagnostic Work Up: PET Scan http://www.hindawi.com/journals/crim/2012/239719/fig2/ https://www.mi-lifenet.com/ImagingCenter/zportal/portals/phys/clinical/petct_case_studies/lymphoma/lymphoma_case3

46. Diagnostic Work Up: Bilateral Bone Marrow Biopsy/Aspirate http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Hodgkin-Lymphoma.aspx#Cancer_Summary

47. Diagnostic Work Up: Least Invasive Biopsy http://www.umphysicians.org/cancercare/cancer-information/cancer-library/CDR269299.html#_1

48. Diagnostic Work Up: Lumbar Puncture http://www.webmd.com/cancer/tc/brain-cancer-primary-central-nervous-system-lymphoma-treatment-patient- information-nci-pdq-general

49. Summary of diagnostic work up for Non-Hodgkin Lymphoma? Physical Exam CBC CMP LDH Uric Acid ESR CRP Ferritin EBV titers CMV titers Chest Xray- PA/L CT scan (CAP) PET scan Lumbar puncture Bone marrow aspirate/biopsy Least invasive Biopsy

50. So how do we treat Non-Hodgkin Lymphoma? O Cyclophosphamide (C) O Vincristine (O) O Prednisone (P) O Doxorubicin (A) O Methotrexate (M) O Hydrocortisone (H) O Cytarabine (A)

51. Hodgkin Lymphoma Non-Hodgkin Lymphoma Prognosis and Late Effects Juan PabloNicole Objectives

52. What are prognoses for Lymphoma? > 85% - 93+ % 90-95% localized 60-90% advanced

53. What are Late Effects for Lymphoma? Based on…

55. Late Effects of Chemotherapy- Steroids Reduced bone mineral density (BMD) Avascular necrosis (AVN) Growth asymmetry/ Decreased bone growth Cataracts Dental caries

56. Late Effects of Chemotherapy- Vincristine/Vinblastine Peripheral sensory or motor neuropathy Areflexia Weakness Foot drop Paresthesia Dental caries

57. Late Effects of Chemotherapy- Bleomycin Interstitial pneumonitis Pulmonary fibrosis Dental caries

58. Late Effects of Chemotherapy- Doxorubicin Cardiomyopathy Arrhythmias Subclinical left ventricular dysfunction (by ECHO or MUGA) DOSE correlates with cardiotoxicity Secondary leukemia (AML/MDS) Dental caries

59. Late Effects of Chemotherapy- Etoposide Secondary leukemia (AML/MDS) Dental caries

60. Late Effects of Chemotherapy- Cyclophosphamide Hemorrhagic cystitis Bladder fibrosis Male GU dysfunction/infertility Female GU dysfunction/infertility Cardiomyopathy Secondary leukemia (AML/MDS) Secondary malignancy (solid tumor) Dental caries

61. Late Effects of Radiation to NECK Hypothyroidism

62. Late Effects of Radiation to CHEST Restrictive Lung Disease Late onset breast cancer Cardiac dysfunction Pericarditis Pericardial fibrosis Growth asymmetry Secondary malignancy (solid tumor)

64. O Painless, nontender, firm, rubbery lymph node O Cough O Weight loss O Fever O Night sweats O Pruritus (itching) O Anorexia (appetite loss) O Tiredness/ Lethargy B symptoms

65. Physical Exam CBC CMP LDH Uric Acid ESR CRP Ferritin EBV titers CMV titers Bartonella titers (if + cat exposure) Chest Xray- PA/L CT scan (CAP) Lumbar puncture (if NHL) Bone marrow aspirate/biopsy PET scan Least invasive Biopsy

66. http://www.nejm.org.ezproxy.etsu.edu:2048/doi/pdf/10.1056/NEJMra0904569 Uric Acid Phosphate Potassium Calcium Sodium NO CHANGE

67. Any Questions?