1. Hodgkin’s and non-Hodgkin’s Lymphoma A/Prof Graham Young Senior Staff Specialist Institute of Haematology Royal Prince Alfred Hospital Sydney

7. RISK FACTORS

8. Haemopoiesis AML Lymphoma/ CLL ALL erythroid myeloid megakaryocytic B lymphoid T lymphoid

10. B cell malignancies Pre-B acute lympho- blastic leukaemia B cell lymphoma Chronic lympho- cytic leukaemia Multiple myeloma Progressive B lymphocyte maturation Bone marrow Lymph node, lymph, blood, bone marrow Lymph node, lymph, blood, bone marrow Bone marrow Lymphoid stem cell Maturing B cell many stages Mature B cell Plasma cell

13. Making the diagnosis nodular (follicular) diffuse small cell large cell Indolent Aggressive

14. Hodgkin’s Lymphoma - Staging

15. PET (Positron Emission Tomography) Scan xxxxxx xxx

19. Hodgkin’s Lymphoma - Progress

26. Hodgkin’s Lymphoma – Management Algorithm BIOPSY Tissue STAGING CT/PET PROGNOSTIC FACTORS EARLY STAGE (Favourable) ADVANCED STAGE (Unfavourable) ADVANCED STAGE (Favourable) EARLY STAGE (Unfavourable) ABVD (3) + IFRT ABVD (6) + IFRT ABVD (6 – 8) BEACOPP (6-8)

39. Randomised intergroup trial of first line treatment for patients  60 years with diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) with a CHOP-like regimen with or without the anti-CD20 antibody MabThera – early stopping after first interim analysis M Pfreundschuh, L Trümper, D Ma, A Österborg, R Pettengell, M Trneny, L Shepherd, J Walewski, P-L Zinzani, and M Loeffler for the MabThera International Trial (MInT) Group Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

40. MInT: trial design CD20 + DLBCL 18–60 years IPI 0,1 Stages II–IV, I with bulk 6 x CHOP-like + 30–40 Gy (Bulk, E) 6 x CHOP-like + MabThera + 30–40 Gy (Bulk, E) Randomisation Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

41. Median age (years) 48 47 Histology (%) DLBCL 96 95 other 4 5 Bulky disease (%) 52 49 B-symptoms (%) 29 27 Extranodal involvement (%) 33 32 Chemo n=165 R-Chemo n= 161 MInT Interim Analysis: patient characteristics Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

42. Chemo n=165 R-Chemo n= 161 MInT Interim Analysis: patient characteristics Ann Arbor stage (%) I 19 19 II 55 60 III 12 12 IV 15 9 ECOG performance status (%) 0,1 99 100 2,3 1 - LDH >UNL (%) 29 34 IPI age-adjusted (%) 0 43 45 1 57 55 Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

43. MInT: adverse events* Percentage of patients 57 53 40 39 11 6 8 8 2 3 * Reported toxicity CTC Grades 3 and 4 Chemotherapy MabThera + chemotherapy 60 50 40 30 20 10 0 Total Haematotoxicity Gastrointestinal Infections Nervous system Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

44. MInT Interim Analysis: time to treatment failure p<0.000005  crit =0.00192 * 81% MabThera + chemotherapy 58% Chemotherapy Months Median time of observation: 24 months Probability *  crit for updated interim analysis 1.0 0.8 0.6 0.4 0.2 0 0 5 10 15 20 25 30 35 40 45 50 Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

45. MInT Interim Analysis: overall survival p=0.0026 95% MabThera + Chemotherapy 85% Chemotherapy Months Median time of observation: 24 months Probability 1.0 0.8 0.6 0.4 0.2 0 0 5 10 15 20 25 30 35 40 45 50 Pfreundschuh M, et al., Proc Am Soc Clin Oncol 2004;23:556 (Abstract 6500)

47. ANNUAL NUMBERS OF BLOOD AND MARROW TRANSPLANTS WORLDWIDE 1970-2002 NUMBER OF TRANSPLANTS YEAR 1970 1975 1980 1985 1990 1995 Autologous Allogeneic 2000 1 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000

48. LOCATION OF CENTERS PARTICIPATING IN THE IBMTR / ABMTR 2003 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

49. INDICATIONS FOR BLOOD AND MARROW TRANSPLANTATION IN NORTH AMERICA 2002 TRANSPLANTS 4,500 0 500 1,000 1,500 2,000 Allogeneic (Total N = 7,200) Autologous (Total N = 10,500) 2,500 3,000 4,000 3,500 NHL Multiple Myeloma AML CML MDS / Other Leukemia Neuroblastoma Non- Malignant Disease 7 Breast Cancer ALL CLL Other Cancer Hodgkin Disease

50. PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR HODGKIN DISEASE, 1996-2001 PROBABILITY, % YEARS P = 0.0001 CR1 (N = 226) CR2+ (N = 733) Never in remission (N = 823) Relapse (N = 1,744) 33 100 0 20 40 60 80 0 1 2 3 4 6 5

51. PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR FOLLICULAR NON-HODGKIN LYMPHOMA, 1996-2001 PROBABILITY, % YEARS P = 0.0009 CR1 (N = 174) CR2+ (N = 322) Never in remission (N = 418) Relapse (N = 791) 34 100 0 20 40 60 80 0 1 2 3 4 6 5

52. PROBABILITY OF SURVIVAL AFTER HLA-IDENTICAL SIBLING MYELOABLATIVE TRANSPLANTS FOR FOLLICULAR NON-HODGKIN LYMPHOMA, 1996-2001 PROBABILITY, % YEARS P = NS CR1-3 (N = 79) Never in remission (N = 138) Relapse (N = 193) 35 100 0 20 40 60 80 0 1 2 3 4 6 5

53. PROBABILITY OF SURVIVAL AFTER AUTOTRANSPLANTS FOR DIFFUSE LARGE CELL LYMPHOMA, 1996-2001 PROBABILITY, % YEARS P = 0.0001 CR1 (N = 438) CR2+ (N = 651) Relapse (N = 1,443) Never in remission (N = 986) 36 100 0 20 40 60 80 0 1 2 3 4 6 5

54. PROBABILITY OF SURVIVAL AFTER HLA-IDENTICAL SIBLING MYELOABLATIVE TRANSPLANTS FOR DIFFUSE LARGE CELL LYMPHOMA, 1996-2001 PROBABILITY, % YEARS P = NS CR1-3 (N = 56) Relapse (N = 144) Never in remission (N = 133) 37 100 0 20 40 60 80 0 1 2 3 4 6 5