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Transplantation in Lymphoma

Dr Adrian Bloor Transplant Director. Transplantation in Lymphoma. Are you a believer?. Transplant Outcomes. Summary. A big subject in 20 mins Briefly review rationale for transplantation Autografting Historical results and place in current treatment New data in DLBCL, MCL

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Transplantation in Lymphoma

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  1. Dr Adrian Bloor Transplant Director Transplantation in Lymphoma

  2. Are you a believer?

  3. Transplant Outcomes

  4. Summary • A big subject in 20 mins • Briefly review rationale for transplantation • Autografting Historical results and place in current treatment • New data in DLBCL, MCL • Allografting Follicular NHL • Hodgkin Lymphoma

  5. Autologous Transplantation

  6. Disease Blood count Count Dose intensity Count Time

  7. Autologous Transplantation Williams CD et al J Clin Oncol 2001;19:727 Shouten HC et al J Clin Oncol 2003;21:3918 Dreyling M et al Blood 2005;105:2677 Philip T et al N Engl J Med 1995;333:1540 Schmitz N et al Lancet 2002;359:2065 Linch DC et al Lancet 1993;341:8852

  8. R A N D O M I S E R A N D O M I S E R-ICE Observe Relapsed DLBCL BEAM R-DHAP R maint CORAL - DLBCL • n = 396 • Response rate 63% • Relapse < 12 months (46% vs 88%) • Prior Rituxumab (51% vs 83%) Gisselbrecht C et al J Clin Oncol 2009;27:8509a

  9. CORAL - DLBCL n = 123 3 year OS/EFS 47/30% PET –ve OS 66% EFS 40% Trneny M et al Blood 2009;114:881a

  10. p = sig PET +ve OS 49% EFS 16% CORAL - DLBCL n = 123 3 year OS/EFS 47/30% PET –ve OS 66% EFS 40% Trneny M et al Blood 2009;114:881a

  11. Mantle Cell Lymphoma - Nordic MCL 1 1996-2000 MCL 2 2000-2006 MCL 3 2006-2009 maxi-CHOP x4 R-maxi-CHOP / R-HD-AraC x6 BEAM(C) auto Purged BEAM(C) auto Z-BEAM (no CR) R n = 41 ORR 75% CR 27% 4 yr PFS 15% n = 160 ORR 96% CR 54% 6 yr PFS 66% NRM 5% n = 160 ORR 96% CR 68% NRM 4% Andersen NC et al Eur J Haematol 2003;71:73 Geisler CH et al Blood 2008;112:2687 Kolstad A et al Blood 2009;114:932a

  12. Autograft mortality 1998-2002 Relapse (75%) Organ toxicity (8%) Unknown (2%) Infection (6%) Other (9%) SUM05_20.ppt

  13. Allogeneic Transplantation derived from Bortin MM Transplantation 1970;9:571

  14. Beneficial effect of GvHD Horowitz MM et al Blood 1990;75:555

  15. GvHD and GvDisease DONOR RECIPIENT GvD

  16. GvHD and GvDisease DONOR RECIPIENT GvD

  17. GvHD and GvDisease

  18. Follicular NHL Replacement for autograft? Thomson KJ et al J Clin Oncol 2010;28:3695 Khouri IF et al Blood 2008;111:5530 Montoto S et al Leukemia 2007;21:2324

  19. HL: Winners and Losers

  20. HL: Salvage autografts Schmitz N et al Lancet 2002;359:2065 Linch DC et al Lancet 1993;341:8852

  21. And if it doesn’t work? • MSKCC • 71 patients (1994-2005) • Poor prognosis • Second transplant improves outcome Moskowitz AJ Br J Haematol 2009;146:158

  22. AlloHSCT for poor prognosis?

  23. EMBT matched pair series • 90 patients • >50% refractory relapse • 2 yr NRM >50% (allo) vs 12% (auto) • But.. • GvHD appears beneficial • Relapse rate 13% (allo) vs 69% (auto) AlloHSCT for poor prognosis? Milied N et al J Clin Oncol 1996;14:1291

  24. RIC Allo outcome NRM 12-46% Age, PS, date of transplant Robinson SP et al Haematologica 2009;94:230

  25. Pick a winner • TTF – based on prognostic score • PS • Disease Status • Chemosensitivity • Remission duration • Tumour bulk • Extranodal disease • eg Stanford series 0 1 2 3 Johnston LJ et al Biol Blood Marrow Trans 2000;6:289

  26. Pick a winner Patient A Patient B

  27. Risk Stratification by FI Jabbour E et al Cancer 2007;109:2481 Moskowitz C unpublished

  28. Trials

  29. Trials designed • ReACH • Chemosensitive PET +ve second remission • Siblings donors • PAIReD • Chemorefractory (PET) first or second remission • Matched donors

  30. 100 Incidence / 100,000 0 0 20 40 60 80 Age Patient Selection Extermann M et al Eur J Can 2000;36:453 Havlik R et al Cancer 1994;74(s7):2101 http://seer.cancer.gov/

  31. Conclusions • A big subject in 20 mins • Autologous transplant effective treatment for many patients with relapsed disease • Autografts have no potential for cure • Allogeneic effect exists in lymphoma • Allogeneic transplantation remains developmental in most areas • Ongoing trials in progress • Patient selection essential – but how?

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