Transplantation in Lymphoma

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Transplantation in Lymphoma
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Are you a believer?
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Transplant Outcomes
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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

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Autologous Transplantation
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Dose intensity
Count
Time
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Autologous Transplantation
Indication Trial Median PFS months OS months
Relapsed FL CUP gt36 vs 12 NR vs 46
Transformed FL EBMT NS (vs controls) NS (vs controls)
MCL MCL Network 39 vs 17 NS
Relapsed DLBCL PARMA gt48 vs lt12 NR vs 15
Relapsed HL BNLI/GHDSG gt36 vs lt12 NS
Williams CD et al J Clin Oncol 200119727 Shouten
HC et al J Clin Oncol 2003213918 Dreyling M et
al Blood 20051052677 Philip T et al N Engl J
Med 19953331540 Schmitz N et al Lancet
20023592065 Linch DC et al Lancet 19933418852
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CORAL - DLBCL

• n 396
• Response rate 63
• Relapse lt 12 months (46 vs 88)
• Prior Rituxumab (51 vs 83)

Gisselbrecht C et al J Clin Oncol 2009278509a
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CORAL - DLBCL
n 123 3 year OS/EFS 47/30 PET
ve OS 66 EFS 40
Trneny M et al Blood 2009114881a
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CORAL - DLBCL
n 123 3 year OS/EFS 47/30 PET
ve OS 66 EFS 40
Trneny M et al Blood 2009114881a
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Mantle Cell Lymphoma - Nordic
MCL 3 2006-2009
MCL 1 1996-2000
MCL 2 2000-2006
maxi-CHOP x4
R-maxi-CHOP / R-HD-AraC x6
Z-BEAM (no CR)
BEAM(C) auto
Purged BEAM(C) auto
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 20037173
Geisler CH et al Blood 20081122687 Kolstad A
et al Blood 2009114932a
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Autograft mortality 1998-2002
Relapse (75)
Organ toxicity (8)
Unknown (2)
Infection (6)
Other (9)
SUM05_20.ppt
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Allogeneic Transplantation
derived from Bortin MM Transplantation 19709571
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Beneficial effect of GvHD
Horowitz MM et al Blood 199075555
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GvHD and GvDisease
DONOR
RECIPIENT
GvD
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GvHD and GvDisease
DONOR
RECIPIENT
GvD
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GvHD and GvDisease
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Follicular NHL
Series Follow up n Protocol PFS/OS NRM Extensive cGvHD
UCLH 43 mo 82 FMC 90 (sib) 64 (UD) 8 (sib) 22 (UD) 18
MDACC 60 mo 43 FCR 85 16 36
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HL Winners and Losers
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HL Salvage autografts
Schmitz N et al Lancet 20023592065 Linch DC et
al Lancet 19933418852
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And if it doesnt work?

• MSKCC
• 71 patients (1994-2005)
• Poor prognosis
• Second transplant improves outcome

Moskowitz AJ Br J Haematol 2009146158
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AlloHSCT for poor prognosis?
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AlloHSCT for poor prognosis?
Milied N et al J Clin Oncol 1996141291
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RIC Allo outcome
Centre n Prior HDT Refractory PFS (2-4 yr) OS (2-4 yr)
EBMT 401 67 22 26 (3 yr) 41 (3yr)
Single Centre 32-58 71-100 33-50 8-39 32-64
NRM 12-46 Age, PS, date of transplant
Robinson SP et al Haematologica 200994230
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Pick a winner

• TTF based on prognostic score
• PS
• Disease Status
• Chemosensitivity
• Remission duration
• Tumour bulk
• Extranodal disease
• eg Stanford series

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1
2
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Johnston LJ et al Biol Blood Marrow Trans
20006289
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Pick a winner
Patient A
Patient B
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Risk Stratification by FI
Centre n Technique 3 yr EFS PET ve 3 yr EFS PET -ve
MDACC 211 68 PET 174 Ga 27 52 (PR) 77 (CR)
MSKCC 160 50 PET 110 Ga 33 74
Jabbour E et al Cancer 20071092481 Moskowitz C
unpublished
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Trials
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Trials designed

• ReACH
• Chemosensitive PET ve second remission
• Siblings donors

• PAIReD
• Chemorefractory (PET) first or second remission
• Matched donors

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Patient Selection
Extermann M et al Eur J Can 200036453 Havlik R
et al Cancer 199474(s7)2101 http//seer.cancer.g
ov/
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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?