1. Childhood Hodgkin Lymphoma Cases and Controversies Eurasian Commonwealth Online Conference 5/25/05 Scott Howard, MD, MSc St. Jude Children’s Research Hospital

2. Relapsed HL Evaluation Above the diaphragm Chest radiograph, Computed tomography Below the diaphragm Computed tomography or ultrasonography Tumor activity (Functional imaging) Gallium scan 18 FDG Positron emission tomography (PET)

3. Relapsed HL Evaluation Bone marrow biopsies All patients Bone scanIf there is bone pain, elevated alkaline phosphatase, or other sites of extranodal disease

4. Relapsed HL Evaluation Lymph node biopsy or fine needle aspirate Relapse therapy should NEVER be started without histologic confirmation of relapse. Evaluation of suspected relapse is the ONLY time a fine needle aspirate should be used for diagnosis of lymphoma in children.

5. Relapsed Hodgkin Lymphoma Treatment Depends on initial treatment –Low-intensity (< 4 chemo cycles) –High-intensity (>4 cycles + RT) Depends on the timing of relapse –PD on therapy, early, late, very late Depends on the extent of relapse –Localized versus extensive Depends on the site of relapse –Nodal versus extranodal

6. Treatment of HL after First Relapse Standard salvage regimen Intensive salvage regimen

7. Relapsed Hodgkin Lymphoma Treatment Depends on initial treatment –Low-intensity (< 4 chemo cycles) –High-intensity (>4 cycles + RT) Depends on the timing of relapse –PD on therapy, early, late, very late Depends on the extent of relapse –Localized versus extensive Depends on the site of relapse –Nodal versus extranodal

8. Treatment of HL after First Relapse Standard salvage regimen –Similar to initial therapy for advanced stage disease –6-8 cycles of chemotherapy –Radiation therapy 20-30 Gy Intensive salvage regimen –Intense cytoreduction –Very intense consolidation (with stem cell rescue) –Radiation therapy 20-36 Gy

9. Pediatric Hodgkin Lymphoma Initial Treatment Regimens MOPP and derivatives –COPP, ChlVPP, CVPP, OPPA ABVD and derivatives –OEPA, DBVE, VBVP, VAMP Stanford V BEACOPP

10. Treatment of HL after First Relapse Standard salvage regimen –Similar to initial therapy for advanced stage disease –6-8 cycles of chemotherapy –Radiation therapy 20-30 Gy Intensive salvage regimen –Intense cytoreduction –Very intense consolidation (with stem cell rescue) –Radiation therapy 20-36 Gy

11. Relapsed Hodgkin Lymphoma Treatment Schema Induction (cytoreduction) Consolidation #1 –chemotherapy vs –high dose chemotherapy with autologous stem cell rescue Consolidation #2 –radiation therapy

12. Treatment Schema for Relapsed HL Cytoreduction (Chemotherapy) Consolidation 1 (Intense Chemotherapy) Consolidation 2 (RT) CR or nice PR No PD

13. Cytoreduction Regimens ICE: Ifosfamide, Carboplatin, Etoposide MIED: High-dose MTX, Ifosfamide, Etoposide, Dexamethasone MIME: Methylguazone, Ifosfamide, Methotrexate, Etoposide ESHAP/ASHAP: Etoposide/Adriamycin, Solumedrol, High-dose-AraC, Cisplatin IV: Ifosfamide/vinorelbine GV: Gemcitibine/vinorelbine

14. Relapsed Hodgkin Lymphoma Case Presentation Multiple relapses in a 16 year old who received incorrect initial treatment

15. Relapsed Hodgkin Lymphoma Case Presentation #1 18421 16 YOHF diagnosed with stage IIA mixed cellularity HL in 8/99 Sites: bilateral cervical, paratracheal Treatment: –8/99-10/99 COPP/ABVD x 2 “cycles” –10/99 XRT 10 cGy in 2 fractions to bilateral neck –10/99-3/00 COPP/ABVD x 4 “cycles” –4/00 No evidence of disease

16. Relapsed Hodgkin Lymphoma Case Presentation #1 18421 Treatment: –4/00 No evidence of disease –4/00-7/00 3 more “cycles” of COPP/ABVD Recurrence #1: 8/2000 New cervical LAD –8/00-10/00 3 “cycles” of COPP/ABVD –11/00 XRT 36 Gy in 20 fractions to mantle, bilateral neck –1/01-2/01 2 “cycles” of MOPP/ABVD –4/01 No evidence of disease

17. Relapsed Hodgkin Lymphoma Case Presentation #1 18421 Recurrence #2: 7/01 New left supraclavicular and axillary LAD –8/01 MIED #1 (CR after cycle #1!) –9/01 MIED #2 –10/01 CYTOP –11/01 XRT 36 Gy to left supraclavicular and axillary area Off-therapy evaluation 12/01

18. Patient 18421 After 2 Relapses (date 9/11/01)

19. Patient 18421 Off Therapy Evaluation (date 12/14/01)

20. Patient 18421 Four months later (3/25/02)

21. Patient 18421 3/25/02

22. Histoplasmosis vs. Relapse

23. Relapsed Hodgkin Lymphoma Case Presentation First relapse in a 13 year old who received VAMP/COP (2 cycles each) + RT 25.5 Gy as initial treatment

24. Relapsed Hodgkin Lymphoma Case Presentation #18012 13 year old white male Left cervical lymphadenopathy –strep negative –monospot negative –s/p multiple courses of antibiotics no soaking night sweats ADHD, weight loss temporal correlation with Ritalin.

25. Relapsed Hodgkin Lymphoma Case Presentation #18012 PE: matted left posterior cervical lymph nodes; 9 cm X 10 cm. ESR 20 LDH 502 mediastinal fullness gallium uptake in left cervical region only bone marrow negative

26. Relapsed Hodgkin Lymphoma Case Presentation #18012 Stage IIA enrolled on HOD 99 2 cycles VAMP 2 cycles COP 2550 mantle irradiation

27. Relapsed Hodgkin Lymphoma Case Presentation #18012 6 month off-therapy evaluation left cervical lymphadenopathy 1.2 x 1.5 cm on exam needle biopsy : Hodgkin disease restaging: localized recurrence, gallium negative

28. 18012 3-25-02

29. 2/7/2002

31. Relapsed Hodgkin Lymphoma Case Presentation First relapse in a 21 year old who received VAMP/COE (2 cycles each) + RT 25.5 Gy as initial treatment

32. Relapsed Hodgkin Lymphoma Case Presentation #19090 21 YOWF with Stage IIA nodular sclerosing HL (intermediate risk) diagnosed 5/17/02 Enrolled on Hod 99  4 cycles of VAMP/COE + modified mantle RT (25.5 Gy) Completed treatment 11/13/02 Relapse 1/8/04 in porta hepatis and para-aortic lymph nodes

33. Relapsed Hodgkin Lymphoma Case Presentation #19090 MIED x 2 cycles (1/19/04-1/24/04 and 2/4/04-2/9/04)  30% tumor shrinkage, PET negative Stem cell pheresis on 2/16/04 ICE x 2 cycles (2/25/04-3/2/04 and 3/19/04-3/24/04)  PR (tumor shrank to 50% of initial relapse volume)

34. 19090 At relapse 11/6/03

35. Relapsed Hodgkin Lymphoma Case Presentation #19090 ICE #2 complicated by hospitalization for febrile neutropenia Incidental PET finding: persistent avidity at the spinous process of C7 Biopsied and found to be necrotic Hodgkin lymphoma (possibly present at diagnosis 18 months prior, when PET scans were not routinely done)

36. Relapsed Hodgkin Lymphoma Case Presentation Progressive disease during therapy in a 16 year old who received VAMP/COE (2 cycles each) as initial treatment

37. Relapsed HL Case #20374 16 YOWF with nodular sclerosing Hodgkin lymphoma diagnosed 11/11/03 Lab: normal CBC, normal chemistry and coagulation profiles, ESR 56, CRP 0.8. Sites of disease: bilateral supraclavicular, bilateral anterior cervical, internal mammary, and bilateral paratracheal nodes, and upper mediastinum

38. BP #20374 Gallium and PET avid in the bilateral supraclavicular nodes, mediastinum, and bilateral paratracheal nodes Stage IIA, intermediate risk (because of > 3 sites of disease) Hodgkin lymphoma Started therapy 11/26/03

39. BP #20374 VAMP x 2 cycles, COE x 2 cycles Came for radiation planning – exam ok, CT ok Returned 2 weeks later to start RT Had palpable lymphadenopathy in the left supraclavicular area Biopsy confirmed progressive Hodgkin lymphoma

40. BP #20374 Restaging evaluation: PET-positive enlarged lymph nodes in the left supraclavicular area and mediastinum Treated with MIED x 1  febrile neutropenia, partial response of the neck node by exam MIED #2 in process